Publications by authors named "Stefania Nicola"

32 Publications

Three years of methotrexate and secukinumab: outcomes of psoriatic arthritis in a real-life setting.

J Am Acad Dermatol 2021 Feb 4. Epub 2021 Feb 4.

Università degli studi di Torino - Dipartimento di Scienze Mediche, Turin, Italy; SSDDU Allergologia e Immunologia Clinica, AO Ordine Mauriziano Umberto I di Torino, Turin, Italy. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2021.02.004DOI Listing
February 2021

Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement.

Cells 2020 09 16;9(9). Epub 2020 Sep 16.

Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, 10128 Turin, Italy.

Background: Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility.

Methods: Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-γ, IL-1β, TNF-α, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-β) related cytokines were measured in 29 SSc-patients and 20 healthy-controls.

Results: Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 ( < 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-β, GM-CSF, IL-17 and ET-1 ( < 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1β, IL-17, ET-1 and GM-CSF ( < 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells9092106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564480PMC
September 2020

ARIA-EAACI statement on asthma and COVID-19 (June 2, 2020).

Authors:
Jean Bousquet Marek Jutel Cezmi A Akdis Ludger Klimek Oliver Pfaar Kari C Nadeau Thomas Eiwegger Anna Bedbrook Ignacio J Ansotegui Josep M Anto Claus Bachert Eric D Bateman Kazi S Bennoor Elena Camelia Berghea Karl-Christian Bergmann Hubert Blain Mateo Bonini Sinthia Bosnic-Anticevich Louis-Philippe Boulet Luisa Brussino Roland Buhl Paulo Camargos Giorgio Walter Canonica Victoria Cardona Thomas Casale Sharon Chinthrajah Mübeccel Akdis Tomas Chivato George Christoff Alvaro A Cruz Wienczyslawa Czarlewski Stefano Del Giacco Hui Du Yehia El-Gamal Wytske J Fokkens Joao A Fonseca Yadong Gao Mina Gaga Bilun Gemicioglu Maia Gotua Tari Haahtela David Halpin Eckard Hamelmann Karin Hoffmann-Sommergruber Marc Humbert Nataliya Ilina Juan-Carlos Ivancevich Guy Joos Musa Khaitov Bruce Kirenga Edward F Knol Fanny W Ko Seppo Koskinen Marek L Kowalski Helga Kraxner Dmitry Kudlay Piotr Kuna Maciej Kupczyk Violeta Kvedariene Amir H Abdul Latiff Lan T Le Michael Levin Desiree Larenas-Linnemann Renaud Louis Mohammad R Masjedi Erik Melén Florin Mihaltan Branislava Milenkovic Yousser Mohammad Mario Morais-Almeida Joaquim Mullol Leyla Namazova Hugo Neffen Elisabete Nunes Paul O'Byrne Robyn O'Hehir Liam O'Mahony Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Petr Panzner Nikos G Papadopoulos Gianni Passalacqua Vincenzo Patella Ruby Pawankar Nhân Pham-Thi Bernard Pigearias Todor A Popov Francesca Puggioni Frederico S Regateiro Giovanni Rolla Menachem Rottem Boleslaw Samolinski Joaquin Sastre Jurgen Schwarze Aziz Sheikh Nicola Scichilone Manuel Soto-Quiros Manuel Soto-Martinez Milan Sova Stefania Nicola Rafael Stelmach Charlotte Suppli-Ulrik Luis Taborda-Barata Teresa To Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Omar Usmani Arunas Valiulis Maria Teresa Ventura Giovanni Viegi Theodor Vontetsianos De Yun Wang Sian Williams Gary W K Wong Arzu Yorgancioglu Mario Zernotti Mihaela Zidarn Torsten Zuberbier Ioana Agache

Allergy 2021 Mar 21;76(3):689-697. Epub 2020 Sep 21.

Transylvania University Brasov, Brasov, Romania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361514PMC
March 2021

Do the current guidelines for asthma pharmacotherapy encourage over-treatment?

Expert Opin Pharmacother 2020 08 13;21(11):1283-1286. Epub 2020 May 13.

Personalized Medicine, Asthma and Allergy - Humanitas Clinical and Research Center, IRCCS , Rozzano, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14656566.2020.1759551DOI Listing
August 2020

Breakthroughs in hereditary angioedema management: a systematic review of approved drugs and those under research.

Drugs Context 2019 2;8:212605. Epub 2019 Oct 2.

Dipartimento di Scienze Mediche - SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I di Torino, Torino, Italy.

Hereditary angioedema (HAE) is a rare genetic disorder, characterized by recurrent and unexpected potentially life-threatening mucosal swelling. The impairment underlying HAE could be a defect in C1-inhibitor activity, or in its serum concentration. Patients affected by HAE should be treated with on-demand or prophylactic drugs. Lifelong C1-inhibitor supplementation is sometimes required. In this review, we review the currently approved drugs for HAE due to C1-inhibitor defect and to describe those under research. In particular, we focused on the mechanisms of action, routes of administration, and efficacy of these therapies. A systematic review of the literature was performed using the PubMed database for original articles and clinical trials of HAE treatments from 2005 to 2019. The approved HAE treatments can minimize the risk of death, but they are not effective in complete healing from the disease. The new gene therapies seem to provide promising opportunities for the treatment of hereditary angioedema. However, there are still many unmet needs, including efficacy, route, and timing of administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7573/dic.212605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788388PMC
October 2019

"Characteristics of patients admitted to emergency department for asthma attack: a real-LIFE study".

BMC Pulm Med 2019 Jun 17;19(1):107. Epub 2019 Jun 17.

Allergy and Clinical Immunology Unit, Department of Medical Science, University of Torino and AO Ordine Mauriziano Umberto I, Torino, Italy.

Background: Asthma is a chronic disease affecting 30 million people in Europe under 45y. Poor control of Asthma is the main cause of emergency-department (ED) access, becoming the strongest determinant of the economic burden of asthma management.

Objective: To examine the characteristics of adult patients admitted to ED for acute asthma attack, focusing on previous diagnosis of asthma (DA) and current therapy.

Methods: During a one-year period, a structured questionnaire, assessing asthma diagnosis and management, was administered to all patients admitted for asthma attack, to the ED of a South-Italy town. Only patients with subsequently confirmed asthma were enrolled. The data on oxygen saturation (Sat.O2), heart and respiratory-rate, severity code ED-admission, hospitalization or discharge, had been obtained.

Results: Two hundred one patients (mean 50.3ys), were enrolled. One hundred eighteen had a DA, made 17.5 ± 5.88 years before, and 35.6% had a specialist-examination in the last year. 53.3% of DA-patients used a self-medication before ED access with short-acting-beta-2-agonist and oral-corticosteroids, although none had a written-asthma-action-plan (WAAP). Almost all DA-patients were on regular therapy: inhaled-corticosteroids (ICS) in 61%, associated with LABA in 85%. 16.7% of DA-patients had previous DA-access. The overall hospitalization-rate was 39%, higher in DA compared to unknown asthmatic patients (UA)(p = 0.017). Significant risk factors for hospitalization were Sat-O2 ≤ 94% breathing ambient air (OR9.91, p < 0.001), inability-to-complete a sentence (OR9.42,p < 0.001) and the age (OR1.02,p = 0.049).

Conclusion: Despite the asthma guidelines-recommendation, up to 40% of patients received the asthma diagnosis in ED, only 61% of DA-patients were taking ICS. It is disappointing that DA-patients did not have a WAAP, which could explain the poor patient-self-medication at ED admission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-019-0869-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580601PMC
June 2019

Treatment of psoriatic arthritis with secukinumab: a case series.

J Dermatolog Treat 2018 ;29(sup1):6-8

a Department of Medical Science , University of Turin , Turin , Italy.

Aim: Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting up to 30% of psoriatic patients, worsening patients' quality of life. Secukinumab, a fully humanized monoclonal antibody that selectively inhibits interleukin (IL) 17 A, has been recently approved for the treatment of PsA in adults, alone or in association with methotrexate (MTX). In the secukinumab registration studies, the primary endpoint was evaluated at 24 weeks; whether there is an early response in patients with psoriatic arthritis is not well characterized. Furthermore, the registration studies included a hierarchical analysis of end-points that led to a missing evaluation of many secondary endpoints.

Methods: We report our real-life experience with secukinumab in 13 patients with PsA who did not respond to previous therapies. Our patients underwent clinical evaluation for the assessment of PsA severity and inflammation markers at 4 and 16 weeks.

Results: Clinical scores and laboratory tests improved at week 4 and 16 with rapid remission of psoriatic lesions and improvements of arthritis.

Conclusion: The speed of action of secukinumab and the improvement in the quality of life, underlined by our findings, can be useful in daily clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09546634.2018.1527994DOI Listing
January 2019

Beer anaphylaxis due to coriander as hidden allergen.

BMJ Case Rep 2018 Aug 8;2018. Epub 2018 Aug 8.

Allergy and Clinical Immunology, University of Torino and AO Ordine Mauriziano, Torino, Italy.

Beer is one of the most widely consumed alcoholic beverage all over the world. Although the production and consumption of this beverage is diffuse, allergic reactions are very uncommonly reported, mainly due to wheat, yeast or hops allergy. More recently, many foods and drinks have been flavoured with spices, with a reported increase in allergic reactions. We report on a case of a young woman who experienced anaphylaxis due to coriander-flavoured beer. This is the first case of beer anaphylaxis due to coriander, which had been added to the beer as aromatising substance. As the presence of flavours is not always reported, they may be considered hidden allergens, whenever they are the cause of anaphylaxis to foods or beverages, the patient usually tolerated. In conclusion, allergic reactions to spices have to be considered in the patients with 'idiopathic' anaphylaxis induced by common foods, where spices had been hidden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2018-225562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088294PMC
August 2018

Micronized Cells of the Probiotic Strain Bifidobacterium lactis BS01 Activate Monocyte Polarization: A New Approach.

J Clin Gastroenterol 2018 Nov/Dec;52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S57-S61

Biolab Research S.r.l., Novara, Italy.

Goals: The aim of this research was to evaluate whether micronized cells (MCs) from selected biotherapeutic bacteria have the ability to effectively modulate the polarization of monocyte/macrophage subpopulations to advantageously provide a first line of defense against infections.

Background: Inflammation is a reaction of the host to viral and bacterial infections with the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases. The monocytes/macrophages play a key role in the initiation and resolution of inflammation through different activation programs.

Study: MCs were obtained from Bifidobacterium lactis BS01 strain using a Bioimmunizer extraction protocol. Monocytes were stimulated with the probiotic strain and/or MCs (10 mg/mL) for 24 hours and 5 days. Monocyte/macrophage differentiation was evaluated by cytometry analysis of surface markers and the activity of the 2 subpopulations on oxidative stress was assessed in an in vitro oxidative stress model with a spectrophotometric test.

Results: The MCs have been shown to modulate considerably the 2 subpopulations of human monocytes/macrophages, both the "patrolling subpopulation" and the "inflammatory subpopulation," thus highlighting a strong immunostimulatory effect. In addition, MCs are able to mitigate significantly the oxidative stress induced by homocysteine in an in vitro model.

Conclusions: Our findings suggest that MCs derived from the biotherapeutic strain BS01 could represent a possible therapy aimed to effectively prevent and/or cure viral, bacterial, fungal, or protozoal diseases, as well as prevent and/or treat inflammatory processes triggered by external pathogenic agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000001068DOI Listing
October 2019

New Approach in Acne Therapy: A Specific Bacteriocin Activity and a Targeted Anti IL-8 Property in Just 1 Probiotic Strain, the L. salivarius LS03.

J Clin Gastroenterol 2018 Nov/Dec;52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S78-S81

Biolab Research S.r.l., Novara, Italy.

Goals: The aim of this research was to assess the antibacterial activity of Lactobacillus salivarius LS03 (DSM 22776) against Propionibacterium acnes and its anti-inflammatory properties by inhibiting P. acnes-induced interleukin-8 (IL-8) release.

Background: Acne is the most common skin disease, causing significant psychosocial problems for those afflicted. Currently available agents for acne treatment, such as oral antibiotics, have limited use. Thus, development of novel agents to treat this disease is needed. In the generation of inflammatory lesions, proliferation of P. acnes in the obstructed follicles is critical. The administration of beneficial microorganisms represents a promising approach for treating several skin alterations and can have many favorable effects.

Study: For the inhibition assay, P. acnes was spread on Propionibacter Isolation Agar Base plates, and LS03-soaked disks were placed directly on the agar surface. Peripheral blood mononuclear cells, isolated from healthy volunteers, were preincubated with phytohemagglutinin 1 μg/mL for 1 hour and stimulated with the probiotic strains for 24 hours to simulate an in vitro IL-8 release model. The IL-8 concentration in the supernatants was analyzed in duplicate using ELISA Kit.

Results: L. salivarius LS03 exerted a significant inhibitory capacity against the target pathogen strain. This antagonistic activity was primarily ascribable to the feature of LS03 strain of secreting active bacteriocins against P. acnes. Concerning the IL-8 analysis, 3 different L. salivarius strains were able to inhibit the release of this chemokine by 10% to 25%.

Conclusions: L. salivarius LS03 probiotic strain could be an alternative treatment to antibiotic/anti-inflammatory therapy in subjects presenting acne vulgaris.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000001053DOI Listing
October 2019

Flow Cytometry: Evolution of Microbiological Methods for Probiotics Enumeration.

J Clin Gastroenterol 2018 Nov/Dec;52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S41-S45

Biolab Research S.r.l., Novara, Italy.

Goals: The purpose of this trial was to verify that the analytical method ISO 19344:2015 (E)-IDF 232:2015 (E) is valid and reliable for quantifying the concentration of the probiotic Lactobacillus rhamnosus GG (ATCC 53103) in a finished product formulation.

Background: Flow cytometry assay is emerging as an alternative rapid method for microbial detection, enumeration, and population profiling. The use of flow cytometry not only permits the determination of viable cell counts but also allows for enumeration of damaged and dead cell subpopulations. Results are expressed as TFU (Total Fluorescent Units) and AFU (Active Fluorescent Units). In December 2015, the International Standard ISO 19344-IDF 232 "Milk and milk products-Starter cultures, probiotics and fermented products-Quantification of lactic acid bacteria by flow cytometry" was published. This particular ISO can be applied universally and regardless of the species of interest.

Study: Analytical method validation was conducted on 3 different industrial batches of L. rhamnosus GG according to USP39<1225>/ICH Q2R1 in term of: accuracy, precision (repeatability), intermediate precision (ruggedness), specificity, limit of quantification, linearity, range, robustness.

Results: The data obtained on the 3 batches of finished product have significantly demonstrated the validity and robustness of the cytofluorimetric analysis.

Conclusions: On the basis of the results obtained, the ISO 19344:2015 (E)-IDF 232:2015 (E) "Quantification of lactic acid bacteria by flow cytometry" can be used for the enumeration of L. rhamnosus GG in a finished product formulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000001057DOI Listing
October 2019

Exhaled breath condensate pH and cysteinyl leukotriens in patients with chronic cough secondary to acid gastroesophageal reflux.

J Breath Res 2016 12 22;11(1):016002. Epub 2016 Dec 22.

Respiratory Medicine and Allergology, Department of Clinical and Experimental Medicine, AOU 'Policlinico-Vittorio Emanuele', University of Catania, Catania, Italy. Author to whom any correspondence should be addressed, at Pneumologia Riabilitativa e Allergologia, AOU 'Policlinico-Vittorio Emanuele', Università degli Studi di Catania, Via Santa Sofia 78 (Edificio 4, Piano 2), 95123 Catania, Italy.

Chronic cough is one of the most common clinical problems and it may be secondary to different stimuli and diseases, including low-level physical and chemical stimulation of the esophageal-bronchial reflex, suggestive of cough-reflex hyperresponsiveness, in patients with gastroesophageal reflux; however, it is still debated whether gastroesophageal reflux could induce airway inflammation and acidification. The aim of this study was to investigate airway pH and cysteynil-leukotrienes (Cys-LTs) concentration (a marker of airway inflammation) in exhaled breath condensate (EBC). Patients with chronic cough and for which all known causes, excluding gastroesophageal reflux, had been investigated and ruled out, were enrolled in the study. All patients underwent 24 h pH monitoring, and EBC was collected to assess pH and Cys-LTs concentration. Forty-five patients were included in the study and those with gastroesophageal reflux had significantly lower EBC-pH and higher concentration of EBC-Cys-LTs. There was a linear inverse correlation between EBC-pH values and EBC-Cys-LTs logarithmically transformed, and a multivariate analysis confirmed that the only significant determinat variable of EBC-Cys-LTs was the presence of gastroesophageal reflux. This study adds knowledge on possible mechanisms related to chronic cough associated with gastroesophageal reflux, which seems to be strictly dependent on airway acidification and the production of Cys-LTs, therefore suggesting an underlying neurogenic inflammation with tachykinins involvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1752-7163/11/1/016002DOI Listing
December 2016

The In Vitro Effectiveness of Lactobacillus fermentum Against Different Candida Species Compared With Broadly Used Azoles.

J Clin Gastroenterol 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S171-S174

*Biolab Research Ltd., Novara †Gastroenterology Department, Santa Rita Hospital-Policlinico di Monza, Vercelli, Italy.

Goals: To investigate the possible use of Lactobacillus strains in the prophylaxis and/or adjuvant therapy of acute vulvovaginal candidiasis and other vaginal infections sustained by Candida yeasts.

Background: The incidence of Candida infections has substantially increased in recent years. Treatment of vaginal infections with lactobacilli has a long tradition, starting with Döderlein's description of the vaginal microbiota.

Materials And Methods: We assessed the activity of serially diluted fluconazole and miconazole (from 3 ng/mL to 1 mg/mL) against Candida strains. Serial dilutions of the azoles were prepared in Sabouraud Dextrose Broth in the presence of Candida strains. Broths were incubated under aerobic condition at 30°C, and the optical density was measured at 560 nm. Minimum inhibitory concentration was defined as the lowest concentration of the antibiotic that completely inhibited visible growth.

Results: An evident resistance to the azoles used was recorded for all species of Candida, with the exception of Candida parapsilosis. For this species, a minimum inhibitory concentration ≤1 mg/mL was obtained, thus confirming the slight sensitivity to fluconazole and miconazole.All Lactobacillus strains tested, namely LF5, LF09, LF10, and LF11, have the ability to significantly inhibit the growth of the five species of Candida of at least 4 logarithms. Furthermore, the best result obtained with miconazole on C. parapsilosis is still 2 logarithms lower.

Conclusions: The use of beneficial bacteria, especially lactobacilli, could be regarded as a good alternative for the prevention and treatment of Candida infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000000686DOI Listing
December 2017

The Possible Innovative Use of Bifidobacterium longum W11 in Association With Rifaximin: A New Horizon for Combined Approach?

J Clin Gastroenterol 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S153-S156

*Biolab Research Ltd, Novara †PTP Science Park, Lodi ‡Gastroenterology Department, Santa Rita Hospital-Policlinico di Monza, Vercelli, Italy.

Goals: The aim of the study was to unequivocally demonstrate the nontransmissibility of the genes mediating the resistance of the strain Bifidobacterium longum W11 (LMG P-21586) to rifaximin.

Background: Most antibiotic treatments can induce unfavorable side effects such as antibiotic-associated diarrhea, which is largely attributable to the disruption of the intestinal microbiota. The parallel intake of probiotic bacteria might reduce these events, even if with generally very poor results. In this regard, the use of antibiotic-resistant beneficial bacteria could represent a worthy strategy.

Study: Rifaximin was tested in parallel with rifampicin, rifapentine, and rifabutin, all rifamycin derivates, using 5 different concentrations. Susceptibility tests were performed by the disc diffusion method of Kirby-Bauer, and inhibition zones were measured after incubation at 37°C. B. longum BL03 was used as comparison. The B. longum W11 genome was sequenced on Illumina MiSeq with a 250 PE reads module. After mapping the reads with the reference bacterial genome, the alignment data were processed using FreeBayes software.

Results: B. longum BL03 was inhibited by all antibiotics even at the lowest concentration. In contrast, the W11 strain was inhibited by rifampicin, rifabutin, and rifaximin only at the highest concentration (512 μg/mL). The genomic analysis showed a mutation into the chromosomal DNA. No transposable elements were found, and the genetic locus was not flanked by close mobile genetic elements.

Conclusions: B. longum W11 could be used in combined therapy with rifaximin, thus opening new focused frontiers in the probiotic era while preserving the necessary safety of use for consumers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000000683DOI Listing
December 2017

In Vitro Inhibition of Klebsiella pneumoniae by Lactobacillus delbrueckii Subsp. delbrueckii LDD01 (DSM 22106): An Innovative Strategy to Possibly Counteract Such Infections in Humans?

J Clin Gastroenterol 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S136-S139

*Biolab Research Ltd ‡Probiotical SpA, Novara †Gastroenterology Department, Santa Rita Hospital-Policlinico di Monza, Vercelli, Italy.

Goals: To determine the in vitro antimicrobial activity of selected Lactobacillus strains isolated from the feces of healthy humans against Klebsiella pneumoniae.

Background: Klebsiella is ubiquitous in nature and may colonize the skin, the pharynx, or the gastrointestinal tract of humans. Despite the widespread use of antibiotic molecules with a broad spectrum in hospitalized patients, an increased overall load of klebsiellae as well as the subsequent development of multidrug-resistant strains able to synthesize extended-spectrum beta-lactamase have been registered. These strains are particularly virulent, express capsular-type K55, and have a considerable ability to propagate.

Study: The 4 strains Lactobacillus paracasei LPC01 (CNCM I-1390), Lactobacillus rhamnosus LR04 (DSM 16605), Bifidobacterium longum B2274 (DSM 24707), and Lactobacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106) were tested. The analysis was performed using both a disc-diffusion assay and the broth-dilution procedure, also including an evaluation of the supernatants obtained from a fresh broth culture of each bacterium.

Results: L. delbrueckii subsp. delbrueckii LDD01 demonstrated the best inhibitory results among all the tested strains. The antibacterial activity of the supernatant was retained even after treatment with α-amylase and neutralization with NaOH 1N, thus suggesting the protein structure of the inhibitory molecule. In contrast, it was completely lost after treatment with proteinase K.

Conclusions: Overall results suggest that the inhibitory effect of L. delbrueckii subsp. delbrueckii LDD01 should be attributed to the production of a bacteriocin. This strain may be prospectively useful for strengthening probiotic formulations and possibly counteract infections by K. pneumoniae in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000000680DOI Listing
December 2017

Searching for the Perfect Homeostasis: Five Strains of Bifidobacterium longum From Centenarians Have a Similar Behavior in the Production of Cytokines.

J Clin Gastroenterol 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S126-S130

*Biolab Research Srl ‡Probiotical SpA, Novara †Gastroenterology Department, Santa Rita Hospital-Policlinico di Monza, Vercelli, Italy.

Goals: To investigate the modulation of human cytokines by Bifidobacterium longum strains isolated from Centenarians. In particular, we measured the production of interleukin (IL)-12p70, interferon-γ, IL-17A, and IL-4 from human peripheral blood mononuclear cells after stimulation with live bacteria.

Background: Probiotics may inhibit pathogens and modulate the immune system, bringing a beneficial effect on human health. Among the probiotic strains, bifidobacteria play a key role in the maturation of the host's immune system. At present, only a few comparative data are available on the effects of bifidobacteria associations on cytokine production.

Study: Peripheral blood mononuclear cells were isolated, cultured, and stimulated (ratio 1:1) with B. longum DLBL07, B. longum DLBL08, B. longum DLBL09, B. longum DLBL10, or B. longum DLBL11, either alone or in association. Cytokine production was determined by an enzyme-linked immunosorbent assay.

Results: Both the B. longum DLBL mixture and the individual B. longum DLBL strains induced similar levels of IL-4, interferon-γ, and IL-17A. Under all conditions tested, no IL-12p70 release was detected.

Conclusions: The fact that B. longum strains were obtained from Centenarians suggests a perfect homeostasis between this specific species and the host. Moreover all the B. longum strains from Centenarians used in our study share some biological similarities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000000678DOI Listing
December 2017

Can Probiotics Reduce Diarrhea and Infant Mortality in Africa?: The Project of a Pilot Study.

J Clin Gastroenterol 2016 Nov/Dec;50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S120-S123

*Gastroenterology Department, Santa Rita Hospital-Policlinico di Monza †Department of Gynecology and Obstetrics, Santa Rita Hospital-Policlinico di Monza, Vercelli ‡Biolab Research Ltd, Novara, Italy.

Background: Diarrhea accounts for 9% of the mortality among children under 5 years of age worldwide, and it is significantly associated with malnutrition. Each year, diarrhea kills around 760,000 children under 5 years of age and most of these are in sub-Saharan Africa.In Uganda, the infant mortality rate of 58 per 1000 is unacceptably high, and the major contributors include malnutrition, diarrhea, pneumonia, malaria, prematurity, sepsis, and newborn illnesses.There is an urgent need for intervention to prevent and control diarrheal diseases.

Study Design: Our open-label, randomized controlled study has the primary endpoint of reducing diarrhea and infectious diseases (number of episodes/severity) and the secondary endpoint of decreasing infant mortality. The trial is currently conducted in Luzira, a suburb of Kampala, the capital of Uganda, and in Gulu and Lira, in the north of Uganda.The study is projected to enroll 4000 babies (control=2000 and treatment=2000) who will be followed till 1 year of life. As controls, 2000 babies of the same community are planned to be considered.The probiotic product selected for the trial is composed of 3 designated microorganisms, namely Bifidobacterium breve BR03 (DSM 16604), B. breve B632 (DSM 24706), and Lactobacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106). The concentration of the 3 bacteria is 10 viable cells/strain/daily dose (5 drops).

Perspectives: For a total sample of 4000 babies, the study has an 80% power at a 5% significance level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000000677DOI Listing
December 2017

Screening of different probiotic strains for their in vitro ability to metabolise oxalates: any prospective use in humans?

J Clin Gastroenterol 2014 Nov-Dec;48 Suppl 1:S91-5

Biolab Research Ltd, Novara, Italy.

Background: Oxalate is the salt-forming ion of oxalic acid and can generate oxalate salts combining with various cations, such as sodium, potassium, magnesium, and calcium. Approximately 75% of all kidney stones are composed primarily of calcium oxalate (CaOx) and hyperoxaluria, a condition involving high urinary oxalate concentration, is considered a primary risk factor for kidney stone formation, known as nephrolithiasis. Current therapeutic strategies often fail in their compliance or effectiveness, and CaOx stone recurrence is still common. After an initial stone, there is a 50% chance of forming a second stone within 7 years if the condition is left untreated. The potential therapeutic application of some probiotics, mainly lactobacilli and bifidobacteria, in reducing hyperoxaluria in vivo through intestinal oxalate degrading activity is compelling and initial reports are promising. This study was undertaken to screen different Lactobacillus and Bifidobacterium strains for their capacity to degrade oxalate in vitro using reverse-phase high-performance liquid chromatography (HPLC).

Methods: The oxalate-degrading activity of 13 lactobacilli and 5 bifidobacteria was tested using a novel HPLC method after growth in a broth culture added with 10 mM ammonium oxalate. Experiments were repeated 3 times. Oxalobacter formigenes (DSM 4420) was used as positive reference to validate HPLC oxalate-degrading capability assays.

Results: Lactobacillus strains were more efficient than bifidobacteria in degrading oxalates. L. paracasei LPC09 (DSM 24243) gave the best result, as 68.5% of ammonium oxalate was converted at the end of incubation, whereas the following best converters belong to the L. gasseri and L. acidophilus species. The relatively low conversion rate observed for most bifidobacteria can probably be attributed to intrinsic oxalate toxicity toward this genus.

Conclusions: Humans lack the enzymes needed to directly metabolise oxalate, and this potentially toxic compound is, therefore, managed using alternative pathways. As oxalate-degrading bacteria are present in the endogenous microbiota of the human intestine, although with significant individual differences, it is possible to hypothesise that the administration of selected oxalate-degrading probiotics could be an alternative and innovative approach to reducing the intestinal absorption of oxalate and the resulting urinary excretion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000000228DOI Listing
June 2015

Assessment of the capability of a gelling complex made of tara gum and the exopolysaccharides produced by the microorganism Streptococcus thermophilus ST10 to prospectively restore the gut physiological barrier: a pilot study.

J Clin Gastroenterol 2014 Nov-Dec;48 Suppl 1:S56-61

*Gastroenterology Unit, Maggiore della Carità Hospital †Biolab Research Ltd.

Background: Leaky gut, or intestinal permeability, is the phenomenon of the gut wall exhibiting increased absorbency. It is pretty well recognised that an altered or damaged bowel lining or gut wall may result from unbalanced diet, parasites, infection, or medications and that this allows substances such as toxins, microbes, undigested food, or waste to leak through. As a natural consequence, this prompts the body to initiate an immune reaction leading to potentially severe health conditions. Different strategies may be used to improve, at least temporarily, the physiological intestinal barrier. The use of specific beneficial microorganisms, such as lactobacilli and bifidobacteria, has been suggested as an innovative tool to counteract an improper level of intestinal permeability. The association of bacteria with specific gelling agents, such as gums, may represent an improvement since these molecules are able to form hydrophilic gels that distribute uniformly over the inner intestinal surface. This pilot study was undertaken to evaluate intestinal permeability in subjects treated with a gelling complex, an association of tara gum and the microorganism Streptococcus thermophilus ST10 (DSM 25246), which has a well-demonstrated in vitro ability to synthesise and secrete exopolysaccharides (EPSs).

Methods: Twenty-five healthy subjects were enrolled in this human intervention, double-blind, placebo-controlled, pilot trial (age between 21 and 57 y, mean 37.7±11.2). Subjects were then randomised into 2 groups: group A (13 subjects) was given an active formulation containing 250 mg of tara gum and 1 billion viable cells of S. thermophilus ST10, whereas group B (12 subjects) was given a placebo formulation. All the subjects participating in the study were directed to take 1 dose per day for 30 consecutive days. The presence and concentration of exopolysaccharides (EPSs) in the faeces was determined at time 0 (d0), after 30 days of treatment (d30), and at the end of the 2-week follow-up period (d45). The monosaccharide composition of EPSs was used to quantify the possible contribution of tara gum to the amount of polysaccharides detected in the faecal material. Intestinal permeability was evaluated at the same time by means of the lactitol/mannitol ratio (small intestine permeability) and sucralose concentration (colonic permeability) in urine specimens sampled after specified times. A statistical comparison was made between the concentration of EPSs, the lactulose/mannitol ratio, and the amount of excreted sucralose in the 2 groups at d0, d30, and d45.

Results: In the active group, supplementation with S. thermophilus ST10 and tara gum was able to significantly increase the faecal EPSs concentration compared with placebo (from 0.169 mg/g to 0.633 mg/g after 30 d, P<0.001). An interesting decrease in intestinal permeability, both of the small bowel and in the colon, was also recorded. The L/M ratio diminished from 0.021 in the active group to 0.014 and 0.015 after 30 and 45 days, respectively (P=0.045 and P=0.033 compared with placebo). The sucralose concentration decreased from 35.8 mg to 27.9 mg and 29.1 mg (P=0.038 and P=0.026 compared with placebo) at the end of the supplementation period and after the follow-up, respectively. No significant differences were recorded in the placebo after 30 days or at the end of the follow-up.

Conclusions: The association of the EPSs produced by S. thermophilus ST10 and tara gum seems capable of significantly improving the intestinal functional barrier in healthy subjects. A wider study in subjects presenting impaired gut permeability would be useful in the future to confirm the positive results from this pilot trial. In any case, our findings are consistent with the parallel increase in exopolysaccharide concentration in the faecal material, thus suggesting the effective ability of the strain used to secrete EPSs in the gut lumen. An innovative approach of this type may be useful in helping to restore the physiological barrier by means of a merely natural and mechanical action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000000254DOI Listing
June 2015

Selenium and zinc internalized by Lactobacillus buchneri Lb26 (DSM 16341) and Bifidobacterium lactis Bb1 (DSM 17850): improved bioavailability using a new biological approach.

J Clin Gastroenterol 2012 Oct;46 Suppl:S41-5

Biolab Research Srl, Novara, Italy.

Background: Minerals, often referred to as micronutrients, are one of the 5 fundamental groups of nutrients needed to sustain life. Micronutrient malnutrition affects >50% of the worldwide population. In particular, zinc (Zn) deficiency is considered an emerging public health problem in India and in other developing countries. Selenium (Se) is another trace mineral essential for humans and animals. Dietary Se exists primarily as selenomethionine and selenocysteine. In addition, Se may be present in its inorganic form (selenite) in some vegetables. To increase the daily intake of these minerals, numerous food supplements containing different inorganic and organic forms of Zn or Se are commercially available. At any rate, it is quite well known that inorganic salts have a very low bioavailability. Organic salts, commonly based on gluconate, orotate, citrate, or other molecules, are characterized by a higher systemic effect. The innovative opportunity of using certain species of probiotics enriched with the 2 minerals could represent an interesting alternative to these preparations. Diet integration with bacteria able to internalize Zn and Se may embody a new application of probiotics.

Methods: To overcome the difficulties of in vivo animal or human trials, in this work a cell culture model using Caco-2 cells in bicameral chambers (Transwell system) was developed and validated to quantify the bioavailability of some commercial forms of Se and Zn compared with the organic forms accumulated intracellularly by Lactobacillus buchneri Lb26 (DSM 16341) and Bifidobacterium lactis Bb1 (DSM 17850), respectively.

Results: The experimental data collected demonstrated a significantly higher bioavailability of Se and Zn internalized by L. buchneri Lb26 (DSM 16341) and B. lactis Bb1 (DSM 17850), respectively, compared with the inorganic and even organic forms tested. In particular, the Se accumulated at the intracellular level by L. buchneri Lb26 proved to be 5.9, 9.4, and 65 times more absorbable than sodium selenite, seleno-L-methionine, and seleno-L-cysteine, respectively. In contrast, Zn internalized by B. lactis Bb1 showed an absorption that was >16 times higher by Caco-2 cells compared with zinc gluconate and a 31.5 times higher absorption compared with zinc sulfate. Most notably, Se and Zn internalized by the 2 probiotics studied are the only forms able to reach the Transwell basolateral compartment at a concentration higher than the concentration found in the apical compartment, therefore suggesting a considerably higher in vivo ability to be absorbed into the bloodstream. Both organic and inorganic forms of Se and Zn were predominantly found in the apical compartment, thus demonstrating their poor ability to diffuse into the cell and become bioavailable in all subcellular areas.

Conclusions: The opportunity of delivering minerals in a highly bioavailable form by means of a probiotic bacterium has not been deeply investigated to date. This is the first study reporting quantitative data on the bioavailability and percentage of absorption of minerals internalized by specific probiotics. The most noticeable aspect is the significantly higher absorption of both probiotic Se and Zn compared with their organic forms, with particular reference to seleno-L-methionine, seleno-L-cysteine, and zinc gluconate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0b013e318268861dDOI Listing
October 2012

Assessment of the in vitro inhibitory activity of specific probiotic bacteria against different Escherichia coli strains.

J Clin Gastroenterol 2012 Oct;46 Suppl:S29-32

Biolab Research Srl, Novarese, Italy.

Background: Lactobacilli and bifidobacteria are often associated with health-promoting effects. These live microorganisms, defined as probiotics, are commonly consumed as part of fermented foods, such as yoghurt and fermented milks, or as dietary supplements. Escherichia coli is a gram-negative, rod-shaped bacterium commonly found in the lower intestine of warm-blooded organisms. As a part of the normal gut microbiota, this microorganism colonizes the gastrointestinal tract of animals and humans within a few hours after birth. All E. coli strains can produce a wide variety of biogenic amines responsible for potentially harmful systemic intoxications. Enterohemorrhagic E. coli serotype O157:H7 is a pathotype of diarrhoeagenic strains with a large virulence plasmid pO157 able to produce 1 or more Shiga toxins.

Methods: The overall aim of this study was to determine the inhibitory effects of different strains of probiotics on E. coli serotypes, including E. coli O157:H7 (CQ9485). In particular, the antagonistic activity of 4 Bifidobacterium strains (Probiotical SpA, Italy) and 16 lactic acid bacteria, more specifically 14 Lactobacillus spp. and 2 Streptococcus spp., was assessed against selected E. coli biotypes (ATCC 8739, ATCC 10536, ATCC 35218, and ATCC 25922). The diarrhoeagenic serotype O157:H7 was also tested.

Results: The experimental data collected demonstrated an in vitro significant inhibitory effect of 6 Lactobacillus strains, namely L. rhamnosus LR04, L. rhamnosus LR06, L. plantarum LP01, L. plantarum LP02, L. pentosus LPS01, and L. delbrueckii subsp. delbrueckii LDD01, and 2 Bifidobacterium strains, B. breve BR03 and B. breve B632. The inhibiting extent was slightly different among these strains, with L. delbrueckii subsp. delbrueckii LDD01 showing the highest activity on E. coli O157:H7.

Conclusions: Most of the probiotics studied are able to antagonize the growth of the 5 strains of E. coli tested, including the O157:H7 biotype, well known for their characteristic to produce a wide variety of biogenic amines considered responsible for dangerous systemic intoxications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0b013e31826852b7DOI Listing
October 2012

Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer's disease and its levels correlate with cognitive decline.

J Alzheimers Dis 2010 ;19(4):1143-8

Interdisciplinary Research Center of Autoimmune Diseases, A Avogadro University of Eastern Piedmont, Novara, Italy.

Inflammation is believed to play a role in Alzheimer's disease (AD). Osteopontin (OPN) is a molecule involved in macrophage recruitment and activation and implicated in neurodegeneration. In order to elucidate the role of OPN in AD, we evaluated its levels in serum and cerebrospinal fluid (CSF) of 67 AD patients, 46 frontotemporal dementia (FTD) patients, and 69 controls. We found that OPN levels: i) are significantly increased in the CSF of AD patients; ii) correlate with MMSE score; and iii) are higher in the early disease phases ( 2 years). These findings support a role of OPN in AD pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-2010-1309DOI Listing
July 2010

The 423Q polymorphism of the X-linked inhibitor of apoptosis gene influences monocyte function and is associated with periodic fever.

Arthritis Rheum 2009 Nov;60(11):3476-84

Interdisciplinary Research Centre of Autoimmune Diseases, and University of Eastern Piedmont, Novara, Italy.

Objective: Hereditary periodic fever syndromes (HPFs) develop as a result of uncontrolled activation of the inflammatory response, with a substantial contribution from interleukin-1beta or tumor necrosis factor alpha (TNFalpha). The HPFs include familial Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), TNF receptor-associated syndrome (TRAPS), and cryopyrinopathies, which are attributable to mutations of the MEFV, MVK, TNFRSF1A, and CIAS1 genes, respectively. However, in many patients, the mutated gene has not been determined; therefore, the condition in these patients with an HPF-like clinical picture is referred to as idiopathic periodic fever (IPF). The aim of this study was to assess involvement of X-linked inhibitor of apoptosis (XIAP), which plays a role in caspase inhibition and NF-kappaB signaling, both of which are processes that influence the development of inflammatory cells.

Methods: The XIAP gene (X-linked) was sequenced in 87 patients with IPF, 46 patients with HPF (13 with HIDS, 17 with TRAPS, and 16 with FMF), and 182 healthy control subjects. The expression of different alleles was evaluated by sequencing XIAP-specific complementary DNA mini-libraries and by real-time polymerase chain reaction and Western blot analyses. The functional effect of XIAP on caspase 9 activity was assessed by a fluorimetric assay, and cytokine secretion was evaluated by enzyme-linked immunosorbent assay.

Results: Sequencing disclosed a 1268A>C variation that caused a Q423P amino acid substitution. The frequency of 423Q-homozygous female patients and 423Q-hemizygous male patients was significantly higher in the IPF group than in the control group (69% versus 51%; odds ratio 2.17, 95% confidence interval 1.23-3.87, P = 0.007), whereas no significant difference was detected in the HPF group (59%) compared with controls. In primary lymphocytes and transfected cell lines, 423Q, as compared with 423P, was associated with higher XIAP protein and messenger RNA expression and lower caspase 9 activation. In lipopolysaccharide-activated monocytes, 423Q was associated with higher secretion of TNFalpha.

Conclusion: These results suggest that 423Q is a predisposing factor for IPF development, possibly through its influence on monocyte function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.24905DOI Listing
November 2009

Serum levels of osteopontin are increased in SIRS and sepsis.

Intensive Care Med 2008 Dec 20;34(12):2176-84. Epub 2008 Sep 20.

Department of Clinical and Experimental Medicine, SCDU Anaesthesia and Intensive Care 1, Maggiore della Carità Hospital, "A. Avogadro" University of Eastern Piedmont, Novara, Italy.

Objective: In sepsis, dysregulation of the immune response leads to rapid multiorgan failure and death. Accurate and timely diagnosis is lifesaving and should discriminate sepsis from the systemic inflammatory response syndrome (SIRS) caused by non-infectious agents. Osteopontin acts as an extracellular matrix component or a soluble cytokine in inflamed tissues. Its exact role in immune response and sepsis remains to be elucidated. Therefore, we investigated the role of osteopontin in SIRS and sepsis.

Design: Prospective, observational study.

Setting: Intensive care unit of a university hospital.

Patients And Participants: Fifty-six patients with SIRS or sepsis and 56 healthy subjects were enrolled.

Interventions: We analyzed the serum levels of osteopontin and TH1-TH2 cytokines and investigated the role of osteopontin on interleukin 6 secretion by monocytes.

Measurements And Main Results: Serum osteopontin levels were strikingly higher in patients than in controls and in sepsis than in SIRS, and decreased during the resolution of both the disorders. Receiver operating characteristic curves showed that osteopontin levels have discriminative power between SIRS and sepsis with an area under the curve of 0.796. Osteopontin levels directly correlated with those of interleukin 6 and in vitro, recombinant osteopontin increased interleukin 6 secretion by monocytes in both the absence and presence of high doses of lipopolysaccharide.

Conclusion: These data suggest that osteopontin might be a mediator involved in the pathogenesis of SIRS and sepsis, possibly by supporting interleukin 6 secretion.

Descriptor: 45. SIRS/Sepsis: clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-008-1268-4DOI Listing
December 2008

ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution.

J Neuroimmunol 2007 May 3;186(1-2):193-8. Epub 2007 May 3.

Interdisciplinary Research Center of Autoimmune Diseases and Department of Medical Sciences, "A. Avogadro" University of Eastern Piedmont, Novara, Italy.

Human ICOS is a T cell costimulatory molecule supporting IL10 secretion. A pilot study investigating variations of the ICOS gene 3'UTR detected 8 polymorphisms forming three haplotypes (A, B, C). Haplotype-A and -C displayed the highest difference. Activated T cells from healthy AA homozygotes expressed significantly less ICOS and secreted more IL10 than AC heterozygotes, whereas AB heterozygotes displayed intermediate levels. Analysis of 441 multiple sclerosis patients and 793 controls showed that frequency of AA homozygosity was significantly lower in MS patients with relapsing-remitting onset (N=416) than in controls (OR=0.70). Moreover, AA patients with relapsing-remitting onset had lower relapse rate and multiple sclerosis severity score than non-AA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneuroim.2007.03.022DOI Listing
May 2007

ICOS cooperates with CD28, IL-2, and IFN-gamma and modulates activation of human naïve CD4+ T cells.

Eur J Immunol 2006 Oct;36(10):2601-12

Interdisciplinary Research Center of Autoimmune Diseases and Department of Medical Sciences, "A. Avogadro" University of Eastern Piedmont at Novara, Novara, Italy.

Several sets of data indicate that ICOS regulates cytokine production in activated T cells, but is less effective on naïve T cells. This work evaluates ICOS function in human naïve CD4+ T cells through an assessment of the effect of soluble forms of the ICOS and CD28 physiological ligands on activation driven by anti-CD3 mAb. ICOS strikingly potentiated secretion of IL-2, IFN-gamma, IL-10, and TNF-alpha, but not IL-4, promoted by optimal stimulation of CD3+CD28, and it was the key switching-factor of activation when cells received suboptimal stimulation of CD3+CD28 or stimulation of CD3 alone in the presence of exogenous IL-2. In these conditions, blockade of IL-2 and IFN-gamma showed that ICOS builds up a positive feedback loop with IFN-gamma, which required IL-2 and was inhibited by IL-4. By contrast, in the absence of CD28 triggering or exogenous IL-2, ICOS-induced costimulation mainly supported expression of TGF-beta1 and FoxP3 and differentiation of regulatory T cells capable to inhibit proliferation of naïve CD4+ T cells driven by allogeneic cells. These data suggest that ICOS favors differentiation of Th effector cells when cooperates with appropriate activation stimuli such as CD3+CD28 or CD3+IL-2, whereas it supports differentiation of regulatory T cells when costimulatory signals are insufficient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.200535571DOI Listing
October 2006

Tissue-specific sensitivity to AID expression in transgenic mouse models.

Gene 2006 Aug 3;377:150-8. Epub 2006 May 3.

Human Genome Department, Istituto di Tecnologie Biomediche, CNR, Segrate (MI), Italy.

Activation-induced cytidine deaminase (AID), an enzyme with homology to members of the APOBEC family, is involved in somatic hypermutation (SHM) of immunoglobulin (Ig) genes, either by direct deamination of DNA or by an indirect action through its putative RNA editing activity. AID is able to mutate both Ig-like reporter constructs and selected non-Ig genes in normal B cells and in other cells when ectopically overexpressed in mammalian cells and transgenic mice. However, in spite of the fact that in these transgenic animals AID activity was driven by an ubiquitous promoter, only T lymphomas and lung adenomas occurred. In the present work, we constructed three sets of transgenic mice in which AID was under the control of lck, HTLV-I and MMTV promoters, respectively. The lck/AID mice developed thymic lymphomas with variable but high efficiency, while no tumor was detected in HTLV-I/AID mice after two years of monitoring. Four MMTV/AID founder mice died with an atypical clinical picture, although no mammary tumor was found. These findings suggest that additional factors, present in thymocytes but not in other tissues or in lymphoid cells at different stages of differentiation, are needed for AID to fully manifest its tumorigenic potential in mouse. Alternatively, the display of full AID mutagenic and transforming activity could be related to the existence of physiologic DSBs which occur in both thymocytes and switching B cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2006.03.024DOI Listing
August 2006

Quantitative and functional defects of dendritic cells in classic Kaposi's sarcoma.

Clin Immunol 2006 Jun 9;119(3):317-29. Epub 2006 Mar 9.

Laboratorio di Immunologia, Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Milano, LITA, Via Fratelli Cervi 93, 20090 Segrate, Milan, Italy.

In this study, we investigated whether dendritic cells (DCs) are altered in classic Kaposi's sarcoma (cKS), a lympho-angioproliferative disorder associated with human herpesvirus-8 (HHV-8) infection. By direct analysis of peripheral blood DCs (PBDCs), we demonstrated that cKS patients have lower frequency of myeloid and plasmacytoid DCs than controls. This reduction was greater in patients with advanced stages of disease. PBDCs from cKS patients also showed up-regulated expression of the scavenger receptor CD91 and impaired IL-12 expression. PB monocytes that represent DC precursors in vivo and in vitro showed the same alterations; accordingly, DCs differentiated in vitro from cKS monocytes were similarly affected. The same alterations were induced by addition of cKS plasma during DC differentiation from control monocytes. These results indicate that PBDCs and their precursors are altered in cKS and suggest that soluble circulating factors participate in this process. The study may provide new insights into the pathogenesis of cKS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clim.2006.01.011DOI Listing
June 2006

Hepatitis C virus-specific reactivity of CD4+-lymphocytes in children born from HCV-infected women.

J Hepatol 2005 Sep;43(3):394-402

Dipartimento di Scienze e Tecnologie Biomediche, Cattedra di Immunologia, Università degli Studi di Milano, Lita, via Fratelli Cervi 93, 20090 Segrate (MI), Italy.

Background/aims: T-lymphocyte reactivity against viral antigens may represent the only immunological marker of host contact with a virus. Aim of the present study was to investigate whether vertical exposure to hepatitis C virus (HCV) could activate HCV-specific T-cell responses that may represent a biomarker of previous contact with the virus, and possibly contribute to the low rate of vertical HCV transmission.

Methods: We studied 28 children born from chronically HCV-infected mothers. HCV-specific activation and proliferation of CD4+-lymphocytes and cytokine production were evaluated in cultures of peripheral blood mononuclear cells (PBMCs) stimulated in vitro with HCV-peptides.

Results: HCV-specific CD4+-cell reactivity was observed in 20 out of the 28 children (71%). The proliferation of HCV-specific CD4+-cells was more frequent and vigorous in children than in their mothers. In children, but not in the mothers, activation of CD4+-cells upon stimulation with HCV-peptides was directly correlated with proliferation. Early upon stimulation with HCV-peptides, lymphocytes from children produced lower levels of IL-10 than lymphocytes from the mothers.

Conclusions: Vertical exposure to HCV induces the development of viral-specific CD4+-cell-mediated immune responses, possibly endowed with protective function against infection, which may contribute to the low rate of vertical HCV transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2005.03.022DOI Listing
September 2005