Publications by authors named "Davide Firinu"

49 Publications

Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID): A Multicenter Retrospective Study of Patients From Italian PID Referral Centers.

Front Immunol 2021 10;12:627423. Epub 2021 Mar 10.

Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.

Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) is a severe non-infectious complication of Common Variable Immunodeficiency (CVID), often associated with extrapulmonary involvement. Due to a poorly understood pathogenesis, GLILD diagnosis and management criteria still lack consensus. Accordingly, it is a relevant cause of long-term loss of respiratory function and is closely associated with a markedly reduced survival. The aim of this study was to describe clinical, immunological, laboratory and functional features of GLILD, whose combination in a predictive model might allow a timely diagnosis. In a multicenter retrospective cross-sectional study we enrolled 73 CVID patients with radiologic features of interstitial lung disease (ILD) associated to CVID (CVID-ILD) and 125 CVID patients without ILD (controls). Of the 73 CVID-ILD patients, 47 received a definite GLILD diagnosis while 26 received a clinical-radiologic diagnosis of CVID related ILD defined as uILD. In GLILD group we found a higher prevalence of splenomegaly (84.8 vs. 39.2%), autoimmune cytopenia (59.6 vs. 6.4%) and bronchiectasis (72.3 vs. 28%), and lower IgA and IgG serum levels at CVID diagnosis. GLILD patients presented lower percentage of switched-memory B cells and marginal zone B cells, and a marked increase in the percentage of circulating CD21lo B cells (14.2 vs. 2.9%). GLILD patients also showed lower total lung capacity (TLC 87.5 vs. 5.0%) and gas transfer (DLCO 61.5 vs. 5.0%) percent of predicted. By univariate logistic regression analysis, we found IgG and IgA levels at CVID diagnosis, presence of splenomegaly and autoimmune cytopenia, CD21lo B cells percentage, TLC and DCLO percent of predicted to be associated to GLILD. The joint analysis of four variables (CD21lo B cells percentage, autoimmune cytopenia, splenomegaly and DLCO percent of predicted), together in a multiple logistic regression model, yielded an area under the ROC curve (AUC) of 0.98 (95% CI: 0.95-1.0). The AUC was only slightly modified when pooling together GLILD and uILD patients (0.92, 95% CI: 0.87-0.97). we propose the combination of two clinical parameters (splenomegaly and autoimmune cytopenia), one lung function index (DLCO%) and one immunologic variable (CD21lo%) as a promising tool for early identification of CVID patients with interstitial lung disease, limiting the use of aggressive diagnostic procedures.
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http://dx.doi.org/10.3389/fimmu.2021.627423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987811PMC
March 2021

Orofacial Granulomatosis: Clinical and Therapeutic Features in an Italian Cohort And Review of the Literature.

Allergy 2021 Feb 28. Epub 2021 Feb 28.

Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, Department of Translational Medical Sciences, Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy.

Background: Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation of the soft tissues of maxillofacial region. We explored OFG patients from 10different Italian Centers and summarized the most recent literature data.

Methods: a review ofpatients with OFG was carried out. An extensive online literature search was performed to identify studies reporting diagnosis and management of OFG.

Results: Thirty-nine patients were recruited between January 2018 and February 2020. Most of them (97.4%) displayed involvement of the lipsand 28.2% suffered from Melkersson-Rosenthal Syndrome. Two patients received diagnosis of CD and one patient of sarcoidosis, suggesting secondary OFG.Oral aphthosis and cervical lymphadenopathy were also described.The mean diagnostic delay was 3.4 years.Histological evaluation was performed in 34/39 patients (87.2%); non-caseating granulomas were found in 73.5% of them.Neurological symptoms (28.2%), gastrointestinal symptoms in absence of overt inflammatory bowel disease (IBD) (20.5%) and atopy (35.9%) were also identified. Therapeutic approaches varied among the centers. Steroids (51.3%) were used with good or partial results.Anti-TNF-α and anti-IgE monoclonal antibodieswere used in 6(15.4%) and 1(2.6%) patients, respectively, with variable results. Surgery was the choice for 2 patients with good response.

Conclusions: OFG is a rare and neglected disease showing multiple clinical phenotypes. While early diagnosis is crucial,managementis difficult and highly dependent on the expertise of clinicians due to the lack of international guidelines. There is a need to establishregistry databases and address challenges of long-term management.
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http://dx.doi.org/10.1111/all.14799DOI Listing
February 2021

Allergen immunotherapy: the growing role of observational and randomisedtrial "Real-World Evidence".

Allergy 2021 Feb 14. Epub 2021 Feb 14.

Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS and Department of Biomedical Sciences, Humanitas University, Milan, Italy.

Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT and consequently, a lack of information on how AIT effectively works in real life. To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will usethe RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic "real-world" database using systematic data collection.Based on the current RWE base,and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. There is a need to establish more AIT registries that collect data in a cohesive way, using standardised protocols. This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.
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http://dx.doi.org/10.1111/all.14773DOI Listing
February 2021

Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience.

Front Immunol 2020 4;11:605688. Epub 2020 Dec 4.

Associazione per l'Avanzamento della Ricerca per i Trapianti O.d.V., non profit organisation, Cagliari, Italy.

Aim: SARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.

Method And Materials: We recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.

Results: Male sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0-0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8-8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7-220.6), Pc = 0.024].

Conclusion: The data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.
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http://dx.doi.org/10.3389/fimmu.2020.605688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746644PMC
December 2020

Seroprevalence of SARS-Cov-2 in the setting of a non-dedicated COVID-19 hospital in a low CoV-2 incidence area: Implications for surgery.

Ann Med Surg (Lond) 2020 Dec 3;60:261-262. Epub 2020 Nov 3.

Department of Medical Sciences and Public Health, University of Cagliari, Italy.

The aim of this study was to assess the seroprevalence of SARS-Cov-2 in the setting of a non-dedicated COVID-19 hospital in a low CoV-2 incidence area. We analysed the data of the patients admitted at our surgical department during the period 31st March - June 30, 2020. Among 86 patients included in the study, we found 2 (2.3%) patients positive for both SARS-CoV-2 specific IgM and IgG, 2 (2.3%) for only SARS-CoV-2 specific IgM, and 1 for only SARS-CoV-2 specific IgG. Thus, seroprevalence for SARS-CoV-2 was 5.8%; nasopharyngeal swab was negative in all the cases. Considering the current limitations in sensitivity of nasopharyngeal swab, the uncertainty in the natural history of SARS-CoV2, and the reported prevalence of CoV-2, we think that careful preadmission triage and tests, the use of personal protective equipment and safe management of surgical smoke are mandatory also in our context of low CoV-2 incidence area.
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http://dx.doi.org/10.1016/j.amsu.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607230PMC
December 2020

Deciphering the Genetics of Primary Angioedema with Normal Levels of C1 Inhibitor.

J Clin Med 2020 Oct 23;9(11). Epub 2020 Oct 23.

CeMIA SA, Makriyianni 31, GR-41334 Larissa, Greece.

The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with alterations as well as those with histaminergic acquired angioedema were excluded. A variant pathogenicity curation strategy was followed, including a comparison of the results with those of genotyping 169 patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), and only filtered-in variants were studied further. Among the examined nl-C1-INH-HAE patients, carriers of neither the p.Ala119Ser nor the p.Met379Lys variant were found, whereas the p.Lys330Glu was detected in four (3%) unrelated probands (one homozygote). In total, 182 different variants were curated, 21 of which represented novel mutations. Although the frequency of variants per gene was comparable between nl-C1-INH-HAE and C1-INH-HAE, variants of the and genes were detected only in nl-C1-INH-HAE patients (six and three, respectively). Twenty-seven filtered variants in 23 different genes were detected in nl-C1-INH-HAE more than once, whereas 69/133 nl-C1-INH-HAE patients had compound heterozygotes of filtered variants located in the same or different genes. Pedigree analysis was performed where feasible. Our results indicate the role that alterations in some genes, like , may play in disease pathogenesis, the complex trait that is possibly underlying in some cases, and the existence of hitherto unrecognized disease endotypes.
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http://dx.doi.org/10.3390/jcm9113402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690775PMC
October 2020

Olfactory Function Is Impaired in Patients with Mastocytosis.

J Allergy Clin Immunol Pract 2021 Mar 13;9(3):1359-1364. Epub 2020 Oct 13.

Allergy and Clinical Immunology Unit, Department of Medical Sciences and Public Health, University Hospital "Duilio Casula," Monserrato, Cagliari, Italy. Electronic address:

Background: Mastocytosis is a clinically heterogeneous disorder associated with abnormal mast cell accumulation in different organs. No data are available as regards the assessment of olfactory function and its association with mastocytosis.

Objective: The aim of the study was first to investigate odor threshold, discrimination, and identification in patients with mastocytosis compared with age-matched healthy controls (HC), and furthermore, to correlate olfactory function with the other clinical symptoms of mastocytosis.

Methods: Eighty-one participants were enrolled: 41 patients with mastocytosis (23 males and 18 females; mean age, 47.95 years; standard deviation [SD], 14.7 years) were compared with 40 HC (23 males and 17 females; mean age, 47.88 years; SD, 14.6 years). Olfactory function among participants was evaluated using the "Sniffin' Sticks" test for odor detection threshold (OT), odor discrimination (OD), and odor identification (OI).

Results: Patients with systemic mastocytosis showed a significant decrease in the total olfactory function (Threshold-Discrimination-Identification [TDI] score), OT, OD, and OI compared with HC. A significant negative correlation was observed only between TDI score and serum tryptase concentration (μg/L). No correlation was observed between disease duration versus OT, OD, OI, and TDI score.

Conclusions: Our results suggest that the olfactory function is impaired in patients compared with HC; a significant negative correlation was found between TDI score and the level of serum tryptase. Olfactory dysfunction in mastocytosis may be considered among the clinical manifestations contributing to the burden of this disease.
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http://dx.doi.org/10.1016/j.jaip.2020.09.061DOI Listing
March 2021

Gastrointestinal coronavirus disease 2019: epidemiology, clinical features, pathogenesis, prevention, and management.

Expert Rev Gastroenterol Hepatol 2021 Jan 24;15(1):41-50. Epub 2020 Nov 24.

Colorectal Surgery Unit, Department of Surgical Science, University of Cagliari , Cagliari, Italy.

Introduction: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infection could have direct involvement of the gastrointestinal tract, and in symptomatic cases, gastrointestinal symptoms (diarrhea, nausea/vomiting, abdominal pain) could be very common.

Area Covered: In this article, we reviewed current-published data of the gastrointestinal aspects involved in SARS-CoV-2 infection, including prevalence and incidence of specific symptoms, the presumptive biological mechanism of GI infection, prognosis, clinical management, and public health-related concerns on the possible risk of oral-fecal transmission.

Expert Opinion: Different clues point to direct virus infection and replication in mucosal cells of the gastrointestinal tract. In vitro studies showed that SARS-CoV-2 could enter into the gastrointestinal epithelial cells by the Angiotensin-Converting enzyme two membrane receptor. These findings, coupled with the identification of viral RNA found in stools of patients, clearly suggest that direct involvement of the gastrointestinal tract is very likely. This can justify most of the gastrointestinal symptoms but also suggest a risk for an oral-fecal route for transmission, additionally or alternatively to the main respiratory route.
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http://dx.doi.org/10.1080/17474124.2020.1821653DOI Listing
January 2021

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI), Österreichische Gesellschaft für Pneumologie (ÖGP) in co-operation with the German, Austrian, and Swiss ARIA groups, and the European Academy of Allergy and Clinical Immunology (EAACI).

Authors:
Ludger Klimek Oliver Pfaar Margitta Worm Thomas Eiwegger Jan Hagemann Markus Ollert Eva Untersmayr Karin Hoffmann-Sommergruber Alessandra Vultaggio Ioana Agache Sevim Bavbek Apostolos Bossios Ingrid Casper Susan Chan Alexia Chatzipetrou Christian Vogelberg Davide Firinu Paula Kauppi Antonios Kolios Akash Kothari Andrea Matucci Oscar Palomares Zsolt Szépfalusi Wolfgang Pohl Wolfram Hötzenecker Alexander R Rosenkranz Karl-Christian Bergmann Thomas Bieber Roland Buhl Jeroen Buters Ulf Darsow Thomas Keil Jörg Kleine-Tebbe Susanne Lau Marcus Maurer Hans Merk Ralph Mösges Joachim Saloga Petra Staubach Uta Jappe Klaus F Rabe Uta Rabe Claus Vogelmeier Tilo Biedermann Kirsten Jung Wolfgang Schlenter Johannes Ring Adam Chaker Wolfgang Wehrmann Sven Becker Laura Freudelsperger Norbert Mülleneisen Katja Nemat Wolfgang Czech Holger Wrede Randolf Brehler Thomas Fuchs Peter-Valentin Tomazic Werner Aberer Antje-Henriette Fink-Wagner Fritz Horak Stefan Wöhrl Verena Niederberger-Leppin Isabella Pali-Schöll Wolfgang Pohl Regina Roller-Wirnsberger Otto Spranger Rudolf Valenta Mübecell Akdis Paolo M Matricardi François Spertini Nicolai Khaltaev Jean-Pierre Michel Larent Nicod Peter Schmid-Grendelmeier Marco Idzko Eckard Hamelmann Thilo Jakob Thomas Werfel Martin Wagenmann Christian Taube Erika Jensen-Jarolim Stephanie Korn Francois Hentges Jürgen Schwarze Liam O Mahony Edward F Knol Stefano Del Giacco Tomás Chivato Pérez Jean Bousquet Anna Bedbrook Torsten Zuberbier Cezmi Akdis Marek Jutel

Allergol Select 2020 7;4:53-68. Epub 2020 Sep 7.

European Academy of Allergy and Clinical Immunology (EAACI).

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials And Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
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http://dx.doi.org/10.5414/ALX02166EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480069PMC
September 2020

Relevance of Essential Trace Elements in Nutrition and Drinking Water for Human Health and Autoimmune Disease Risk.

Nutrients 2020 Jul 13;12(7). Epub 2020 Jul 13.

Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, 09042 Cagliari, Italy.

Trace elements produce double-edged effects on the lives of animals and particularly of humans. On one hand, these elements represent potentially toxic agents; on the other hand, they are essentially needed to support growth and development and confer protection against disease. Certain trace elements and metals are particularly involved in humoral and cellular immune responses, playing the roles of cofactors for essential enzymes and antioxidant molecules. The amount taken up and the accumulation in human tissues decisively control whether the exerted effects are toxic or beneficial. For these reasons, there is an urgent need to re-consider, harmonize and update current legislative regulations regarding the concentrations of trace elements in food and in drinking water. This review aims to provide information on the interrelation of certain trace elements with risk of autoimmune disease, with a particular focus on type 1 diabetes and multiple sclerosis. In addition, an overview of the current regulations and regulatory gaps is provided in order to highlight the importance of this issue for everyday nutrition and human health.
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http://dx.doi.org/10.3390/nu12072074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400883PMC
July 2020

Management of Intermittent and Persistent Asthma in Adolescent and High School Athletes.

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2166-2181

Program in Human Nutrition, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.

Asthma is the most common chronic condition during childhood and adolescence, affecting an estimated 8% of children and youngsters below 18 years in the United States and the United Kingdom. In adolescent athletes, asthma-like symptoms may represent a common consequence of regular sport practice. Asthma in young athletes poses several challenges, including the ambiguity of definitions and diagnosis of asthma resulting from exercise-induced symptoms, the best pharmacological treatments, and the nonpharmacological options for the management of disease and the challenges inherent to this age group. At a time when the regular practice of sports is increasingly being recommended for a healthy living, the support network around the young athletes is crucial to reduce the impact of asthma on their physical and emotional well-being. In this review, we examine the main issues around the definitions and clinical differentiations of asthma in young sport athletes. We discuss best practice approaches to improve the adherence to the clinical management, including nonpharmacological strategies directed at the family and trainers of athlete adolescents.
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http://dx.doi.org/10.1016/j.jaip.2020.05.003DOI Listing
March 2020

Top-Down Proteomics of Human Saliva Discloses Significant Variations of the Protein Profile in Patients with Mastocytosis.

J Proteome Res 2020 08 6;19(8):3238-3253. Epub 2020 Jul 6.

Dipartimento di Scienze della Vita e dell'Ambiente, Università di Cagliari, 09124 Cagliari, Italy.

Mastocytosis is a myeloproliferative neoplasm causing abnormal clonal mast cell accumulation in different tissues, such as skin and bone marrow. A cutaneous subtype (CM) is distinguished from a systemic one (SM); SM patients can be grouped into SM with (SM+C) or without (SM-C) additional cutaneous lesions, and their classification is often challenging. This study was purposed to highlight variations in the salivary proteome of patients with different mastocytosis subtypes and compared to healthy controls. A top-down proteomics approach coupled to a label-free quantitation revealed salivary profiles in patients different from those of controls and a down-regulation of peptides/proteins involved in the mouth homeostasis and defense, such as statherin, histatins, and acidic proline-rich proteins (aPRPs), and in innate immunity and inflammation, such as the cathepsin inhibitors, suggesting a systemic condition associated with an exacerbated inflammatory state. The up-regulation of antileukoproteinase and S100A8 suggested a protective role against the disease status. The two SM forms were distinguished by the lower levels of truncated forms of aPRPs, statherin, P-B peptide, and cystatin D and the higher levels of thymosin β4 and α-defensins 1 and 4 in SM-C patients with respect to SM+C. Data are available via ProteomeXchange with identifier PXD017759.
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http://dx.doi.org/10.1021/acs.jproteome.0c00207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008451PMC
August 2020

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Zentrum für Rhinologie & Allergologie, An den Quellen 10, 65183 Wiesbaden, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

Proteomic Analysis of the Acid-Insoluble Fraction of Whole Saliva from Patients Affected by Different Forms of Non-histaminergic Angioedema.

J Clin Immunol 2020 08 10;40(6):840-850. Epub 2020 Jun 10.

Dept of Life and Environmental Sciences, University of Cagliari, 09042, Monserrato, CA, Italy.

We analyzed by bidimensional electrophoresis the acid-insoluble fraction of saliva from three classes of angioedema patients and a healthy control group, highlighting significant variations of several normalized spot volumes. Characterization of the corresponding proteins was performed by in-gel tryptic digestion of the spots, followed by high-resolution HPLC-ESI-MS/MS analysis of tryptic mixtures. By this strategy, 16 differentially-expressed proteins among two or more groups were identified. We found higher concentration of proteins involved in immune response (interleukin-1 receptor antagonist and annexin A1), and of moonlighting proteins acting as plasminogen receptors (glyceraldehyde-3-phosphate dehydrogenase, α-enolase, and annexin A2) in patients affected by the idiopathic non-histaminergic or hereditary angioedema with unknown origin with respect to healthy controls. These data provide new information on the molecular basis of these less characterized types of angioedema. Graphical Abstract Graphical Abstract.
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http://dx.doi.org/10.1007/s10875-020-00802-wDOI Listing
August 2020

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement.

Allergy 2020 11;75(11):2764-2774

Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON, Canada.

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
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http://dx.doi.org/10.1111/all.14407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300800PMC
November 2020

EAACI Biologicals Guidelines-Recommendations for severe asthma.

Allergy 2021 01 10;76(1):14-44. Epub 2020 Aug 10.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.
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http://dx.doi.org/10.1111/all.14425DOI Listing
January 2021

Serum Free Light Chains in Common Variable Immunodeficiency Disorders: Role in Differential Diagnosis and Association With Clinical Phenotype.

Front Immunol 2020 31;11:319. Epub 2020 Mar 31.

Department of Medicine-DIMED, University of Padova, Padova, Italy.

We report on an observational, multicenter study of 345 adult CVID patients, designed to assess the diagnostic value and the clinical association of serum free light chain (sFLC) pattern in Common Variable Immunodeficiency disorders (CVID). Sixty CVID patients were tested twice in order to assess intraindividual variability of sFLC. As control groups we included 138 patients affected by undefined primary antibody defects (UAD), lymphoproliferative diseases (LPDs), and secondary antibody deficiencies not related to hematological malignancies (SID). CVID patients presented lower κ and λ chain concentration compared to controls, showing low intraindividual sFLC variability. On the basis of the sFLC pattern, patients were classified into four groups: κ-λ+, κ+λ-, κ-λ-, κ+λ+. The most common pattern in CVID patients was κ-λ- (51%), followed by κ-λ+, (25%), κ+λ+ (22%), and κ+λ- (3%). In UAD, LPD, and SID groups κ+λ+ was the most common pattern observed. By analyzing the possible association between sFLC patterns and disease-related complications of CVID, we observed that patients belonging to the κ-λ- group presented more commonly unexplained enteropathy compared to the κ+λ+ group and showed higher frequency of bronchiectasis and splenomegaly compared to both the κ-λ+ and κ+λ+ patients. When compared to the other groups, κ-λ- had also lower serum IgG, IgA, and IgM concentrations at diagnosis, lower frequency of CD27+IgD-IgM- switched memory B cells, and higher frequency of CD21 B cells, receiving earlier CVID diagnosis. Thus, lower levels of sFLC might be an epiphenomenon of impairment in B cell differentiation, possibly leading κ-λ- patients to a higher risk for bacterial infections and chronic lung damage. Based on these results, we suggest adding sFLC assay to the diagnostic work-up of hypogammaglobulinemia and during follow-up. The assay may be useful to differentiate CVID from other causes of hypogammaglobulinemia and to early detect monoclonal lymphoproliferation occurring over years. Moreover, since the sFLC pattern seems to be related to disease phenotypes and clinical manifestations of CVID and after confirmation by further studies, sFLC assay might be considered a promising prognostic tool for identifying patients at higher risk of developing enteropathy and chronic lung damage or splenomegaly. This will allow designing a tailored follow-up for CVID patients.
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http://dx.doi.org/10.3389/fimmu.2020.00319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136404PMC
March 2021

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma.

Allergy 2020 05 1;75(5):1058-1068. Epub 2020 Apr 1.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor α, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) -28.2 mg/d; 95% CI -40.7 to -15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD -0.28 (95% CI -0.39 to -0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD -0.35 (95% CI -0.73 to +0.02). FEV increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.
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http://dx.doi.org/10.1111/all.14268DOI Listing
May 2020

Oxidative stress in hereditary angioedema caused by C1 inhibitor deficiency: an interesting finding that deserves further studies.

Pol Arch Intern Med 2020 02 27;130(2):73-75. Epub 2020 Feb 27.

Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy

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http://dx.doi.org/10.20452/pamw.15213DOI Listing
February 2020

Baricitinib exposure during pregnancy in rheumatoid arthritis.

Ther Adv Musculoskelet Dis 2020 3;12:1759720X19899296. Epub 2020 Feb 3.

Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital "Duilio Casula", University of Cagliari, Cagliari, Italy.

We here describe the case of a 43-year-old White woman who was diagnosed with rheumatoid arthritis treated with anti-tumour necrosis factor drugs that caused an adverse drug reaction. The objective of this study was to describe the outcome of a pregnancy under baricitinib, a JAK-inhibitor drug, in a woman affected by rheumatoid arthritis. Scant data are available about the safety of JAK inhibitors during pregnancy. A case report and review of literature about JAK-inhibitor exposure during pregnancy were conducted. After the failure of biologic disease-modifying antirheumatic drugs due to a loss of efficacy and adverse drug reaction, the patient was started on baricitinib when it was marketed. During the fifth month of this treatment, she reported missing her period and a pregnancy was confirmed, despite a previous recommendation of adequate contraception. Thus, she had been exposed to baricitinib for several weeks before conception and during the whole first-trimester until the 17th week of gestation. The treatment with baricitinib was promptly discontinued and she was regularly examined. Foetal growth was normal throughout pregnancy and ultrasound examination did not detect any macroscopic abnormality. This is the first report of exposure to baricitinib during pregnancy outside the drug registration study program. We report the positive pregnancy outcome of a continuous exposure to baricitinib during the first 17 weeks of pregnancy. Small molecules, such as JAK inhibitors, are increasingly being used in clinical practice in rheumatoid arthritis and in other diseases. Hence, more broad and focused studies are required to have an insight of safety for this drug class in the case of accidental exposure before or during pregnancy.
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http://dx.doi.org/10.1177/1759720X19899296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997965PMC
February 2020

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Allergy 2020 05;75(5):1043-1057

University of Wroclaw, Department of Clinical Immunology, Wroclaw, Poland.

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 - 0.81); dupilumab IRR 0.58 (95%CI 0.47 - 0.73); and omalizumab IRR 0.56 (95%CI 0.42 - 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 -1.83)], reduced ICS [mean difference (MD) -0.45 (95% CI -0.58 to -0.32)] and rescue medication use [ MD -0.41 (95%CI -0.66 to -0.15)].
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http://dx.doi.org/10.1111/all.14235DOI Listing
May 2020

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Allergy 2020 05 24;75(5):1023-1042. Epub 2020 Feb 24.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV . More data on long-term safety are needed together with more efficacy data in the paediatric population.
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http://dx.doi.org/10.1111/all.14221DOI Listing
May 2020

Vaping effects on asthma: results from a web survey and clinical investigation.

Intern Emerg Med 2020 06 20;15(4):663-671. Epub 2020 Jan 20.

Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, Asse Didattico "E1", 09042, Monserrato, Cagliari, Italy.

It is well known that tobacco smoking worsens asthma. Conversely, few data are currently available in the literature on the effects of vaping in asthmatic patients. This work aims to investigate the effects of vaping on asthmatic patients and in asthmatic patients that switched from tobacco smoking to electronic cigarette (e-cig), in particular focusing on quality of life, asthma control, and pulmonary function. We designed a two-group study. One group encompassed vapers with asthma selected through a web survey with questions on quality of life and symptoms worsening; the other group encompassed vapers that switched from tobacco smoking to e-cig, and that volunteered to undergo clinical visits at our outpatient clinic. 2787 people responded to the web survey, including 631 asthmatics. In the second group, 55 volunteers, including 15 asthmatics, were enrolled after a visit. The visit included physical examination and pulmonary function tests (PFT). Internationally validated questionnaires were administered to all subjects: Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), 36-Item Short Form Survey (SF-36) and Asthma Quality of Life Questionnaire (AQLQ). The 382 asthmatic vapers-only in the web survey were mainly males (86.9%), 31-65 years old. 90% of them declared that vaping did not worsen asthma symptoms and would recommend asthmatic smokers to switch to vaping (98.4%). There was worsening of asthma symptoms due to the actual asthma therapy used by the participants, while no relationship was found with other aspects analysed. In the second group, the analysis of variance in the questionnaires administered to the 10 asthmatics showed a significant improvement in ACQ, ACT and SF-36 for asthmatics that switched from tobacco to vaping, while PFT remained stable throughout the three visits. Almost all of the asthmatics who previously smoked would recommend switching to e-cig, and vaping did not worsen their asthma symptoms. Furthermore, switching from tobacco smoking to e-cigs showed a significant improvement in asthma control and quality of life, not showing, in the period studied, to affect pulmonary function tests.
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http://dx.doi.org/10.1007/s11739-019-02247-5DOI Listing
June 2020

RP-HPLC-ESI-IT Mass Spectrometry Reveals Significant Variations of the Human Salivary Protein Profile Associated with Predominantly Antibody Deficiencies.

J Clin Immunol 2020 02 8;40(2):329-339. Epub 2020 Jan 8.

Department of Life and Environmental Sciences, University of Cagliari, Cittadella Univ. Monserrato, ss 554, 09042, Monserrato, CA, Italy.

Purpose: Present study is designed to discover potential salivary biomarkers associated with predominantly antibody deficiencies, which include a large spectrum of disorders sharing failure of antibody production, and B cell defects resulting in recurrent infections, autoimmune and inflammatory manifestations, and tumor susceptibility. Understanding and clinical classification of these syndromes is still challenging.

Methods: We carried out a study of human saliva based on liquid chromatography-mass spectrometry measurements of intact protein mass values. Salivary protein profiles of patients (n = 23) and healthy controls (n = 30) were compared.

Results: Patients exhibited lower abundance of α-defensins 1-4, cystatins S1 and S2, and higher abundance of glutathionylated cystatin B and cystatin SN than controls. Patients could be clustered in two groups on the basis of different levels of cystatin SN, S1 and S2, suggesting that these proteins may play different roles in the disease.

Conclusions: Quantitative variations of these pro-inflammatory and antimicrobial peptides/proteins may be related to immunodeficiency and infectious condition of the patients. The high incidence of tumors in the group with the highest level of cystatin SN, which is recognized as tumoral marker, appeared an intriguing result deserving of future investigations. Data are available via ProteomeXchange with identifier PXD012688.
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http://dx.doi.org/10.1007/s10875-020-00743-4DOI Listing
February 2020

Impaired control of the contact system in hereditary angioedema with normal C1-inhibitor.

Allergy 2020 06 6;75(6):1394-1403. Epub 2020 Feb 6.

Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.

Background: Hereditary angioedema (HAE) comprises HAE with C1-inhibitor deficiency (C1-INH-HAE) and HAE with normal C1-INH activity (nl-C1-INH-HAE), due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 genes (KNG1-HAE), or angioedema of unknown origin (U-HAE). The Italian network for C1-INH-HAE (ITACA) created a registry including different forms of angioedema without wheals.

Objective: We analyzed clinical and laboratory features of a cohort of Italian subjects with nl-C1-INH-HAE followed by ITACA to identify specific biomarkers.

Methods: A total of 105 nl-C1-INH-HAE patients were studied. Plasma concentrations of cleaved high-molecular-weight kininogen (cHK), vascular endothelial growth factors (VEGFs), angiopoietins (Angs), and secreted phospholipase A enzymes (sPLA ) were evaluated.

Results: We identified 43 FXII-HAE patients, 58 U-HAE, and 4 ANGPT1-HAE. We assessed a prevalence of 1:1.4 × 10 for FXII-HAE and 1:1.0 × 10 for U-HAE. cHK levels in U-HAE patients were similar to controls in plasma collected using protease inhibitors cocktail (PIC), but they significantly increased in the absence of PIC. In FXII-HAE patients, cHK levels, in the absence of PIC, were significantly higher than in controls. We found a significant increase of VEGF-A, VEGF-C, and Ang1 levels in U-HAE patients compared to controls. In FXII-HAE, only VEGF-C levels were increased. Ang2 concentrations and sPLA activity were not modified. The levels of these mediators in ANGPT1-HAE patients were not altered.

Conclusions: Our results suggest that pathogenesis of FXII-, ANGPT1-, and U-HAE moves through an unbalanced control of kallikrein activity, with bradykinin as most likely mediator. VEGFs and Ang1 participate in the pathophysiology of U-HAE increasing the basal vascular permeability.
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http://dx.doi.org/10.1111/all.14160DOI Listing
June 2020

Clinical pitfalls of leishmaniasis and Whipple's disease hidden behind systemic lupus erythematosus: A case series.

Acta Microbiol Immunol Hung 2019 Sep 17;66(3):377-385. Epub 2019 May 17.

Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital "Duilio Casula", University of Cagliari, Monserrato (Cagliari),Italy.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that can affect major organs possibly leading to life-threatening complications and appears with heterogeneous clinical picture. SLE could present with broad spectrum of clinical and laboratory features that can resemble those of other diseases, such as hemopoietic malignancies, infections, or immune-mediated disorders. Its complexity and protean features overlap with many other diseases, hindering the differential diagnosis. Rarely, true overlap with other diseases may occur. Herein, we report a case series of two patients affected by infectious diseases, namely visceral leishmaniasis and Whipple's disease (WD), intertwined with clinical or serological features of SLE. In both cases, several confounding factors have led to a delay in the diagnosis. Moreover, we first describe the persistent elevation of autoantibodies and a monoclonal gammopathy in a patient with WD. Awareness of unusual presentations of infections or other rare disorders, which may be encountered in clinical practice when taking care of SLE patients, is essential for timely diagnosis and treatment of potentially lethal diseases.
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http://dx.doi.org/10.1556/030.66.2019.013DOI Listing
September 2019

Exercise-induced anaphylaxis with an Ayurvedic drug as cofactor: A case report.

World J Clin Cases 2019 Mar;7(5):623-627

Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital "Duilio Casula", University of Cagliari, Monserrato 09042, Italy.

Background: The practice of Indian Ayurvedic medicine is spreading in Western countries and Shilajit is one of the most used drugs, for its antioxidant activities and immunomodulatory effects. Albeit Shilajit has showed a high degree of safety, it can act as cofactor of anaphylaxis, especially in condition at high risk, such as mast cell activation syndrome (MCAS). We reported this case to sensitize practitioners to investigate to the use of complementary and alternative medicine, in case of exercise-induced anaphylaxis (EIAn).

Case Summary: A 43-year-old woman, working as a dance teacher, developed urticaria after ingestion of rice, tuna and Shilajit, which did not respond to intramuscular corticosteroids. Subsequently, she developed dyspnoea and hypotension with loss of consciousness that arose 1 h after sexual activity. The patient did not refer personal history of atopy. Specific IgE for main food allergens resulted negative, with total IgE levels of 14 IU/L. Oral provocation test with Shilajit was not perfomed because the patient refused, but we performed prick-by-prick and patch test that resulted negative. Serum tryptase at the time of anaphylaxis was 20.6 μg/L that fell down to of 10.6 μg/L after therapy, but has remained at the high value after two days and during the follow-up. We performed an analysis of th gene in peripheral blood, which was negative. We felt the diagnosis consistent with EIAn in a patient with a possible MCAS.

Conclusion: In Western countries the use of drugs from Ayurvedic medicine is more common than in the past. These substances can be cofactors of anaphylaxis in patients with risk factors.
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http://dx.doi.org/10.12998/wjcc.v7.i5.623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406205PMC
March 2019

Is hereditary angioedema related to an increased risk of atherosclerosis?

Ann Allergy Asthma Immunol 2019 02;122(2):228-229

Department of Medical Sciences and Public Health, Unit of Internal Medicine, Allergy and Clinical Immunology, University of Cagliari, Italy.

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http://dx.doi.org/10.1016/j.anai.2018.11.006DOI Listing
February 2019

Oxidative stress markers in patients with hereditary angioedema.

Arch Med Sci 2019 01 31;15(1):92-98. Epub 2017 Jul 31.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Introduction: Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) or with normal C1-INH is characterized by recurrent swellings due to uncontrolled production of vasoactive mediators, among which bradykinin (BK) is crucial. Through the binding and activation of the two human BK-receptors, kinins may have dual beneficial and deleterious effects in vascular and inflammation physiopathology by inducing oxidative stress. We aimed to assess the serum concentrations of advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) in patients affected by HAE.

Material And Methods: Blood samples were collected to measure the serum concentrations of AGEs and AOPPs by spectrofluorimetric and spectrophotometric methods in patients affected by C1-INH-HAE and FXII-HAE during the remission state.

Results: We showed that the circulating levels of AOPPs observed on control group (0.94 (0.36) nmol/mg) were significantly lower than those observed on the C1-INH-HAE group (1.68 (0.47) nmol/mg; = 0.002) and FXII-HAE (1.50 (0.27) nmol/mg; = 0.001). Moreover, the circulating levels of AGEs were significantly higher in C1-INH-HAE group (211.58 (151.05) AU/g; = 0.02) than the FXII group (141.48 (89.59) AU/g), thus demonstrating a state of heightened oxidative stress.

Conclusions: Our observations show additional underlying events involved in HAE and are of central importance for further investigations of differences in bradykinin receptors signaling among the two disease subgroups.
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http://dx.doi.org/10.5114/aoms.2017.66160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348350PMC
January 2019

The role of genetics in the current diagnostic workup of idiopathic non-histaminergic angioedema.

Allergy 2019 04 12;74(4):810-812. Epub 2018 Dec 12.

Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy.

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http://dx.doi.org/10.1111/all.13667DOI Listing
April 2019