Publications by authors named "Boaz Palterer"

21 Publications

  • Page 1 of 1

Evaluation of a novel particle-based multi-analyte technology for the detection of anti-fibrillarin antibodies.

Immunol Res 2021 Apr 28. Epub 2021 Apr 28.

Immunologia E Allergologia, Ospedale S. Maria degli Angeli, Pordenone, Italy.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several anti-nuclear antibodies (ANA), including those in the classification criteria (anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA Pol III). However, the presence of less common antibodies such as anti-fibrillarin (U3-RNP) that generate a clumpy nucleolar pattern by HEp-2 indirect immunofluorescence assay (IFA, ICAP AC-9) are considered disease specific and are with clinical subsets of SSc, therefore playing a role in diagnosis and prognosis. A specific and sensitive anti-fibrillarin assay would be an important addition to serological diagnosis and evaluation of SSc. The goal of this study was to evaluate a new particle-based multi-analyte technology (PMAT) for the measurement of anti-fibrillarin antibodies. A total of 149 patient samples were collected including 47 samples from France (Lyon and Paris, n = 32) and Italy (Careggi Hospital, Florence, n = 15) selected based on AC-9 HEp-2 IFA staining (> 1:640, clumpy nucleolar pattern) and 102 non-SSc controls (inflammatory bowel disease (IBD) n = 20, Sjögren's syndrome (SjS) n = 20, infectious disease (ID) n = 7, systemic lupus erythematosus (SLE) n = 17, rheumatoid arthritis (RA) n = 17, and healthy individuals (HI) n = 21). All samples were tested on the anti-fibrillarin PMAT assay (research use only, Inova Diagnostics, USA). Additionally, the 47 anti-fibrillarin positive samples were also tested on PMAT assays for detecting other autoantibodies in ANA-associated rheumatic diseases (AARD). Anti-fibrillarin antibody data performed by fluorescence enzyme immunoassay (FEIA, Thermo Fisher, Germany) was available for 34 samples. The anti-fibrillarin PMAT assay was positive in 31/32 (96.9%, France) and 12/15 (80.0%, Italy) of samples preselected based on the AC-9 IIF pattern (difference p = 0.09). Collectively, the PMAT assay showed 91.5% (95% confidence interval (CI): 80.1-96.6%) sensitivity with 100.0% (95% CI: 96.4-100.0%) specificity in non-SSc controls. Strong agreement was found between PMAT and FEIA with 100.0% positive qualitative agreement (34/34) and quantitative agreement (Spearman's rho = 0.89, 95% CI: 0.77.9-0.95%, p < 0.0001). Although most anti-fibrillarin positive samples were mono-specific (69.8%), some expressed additional antibodies (namely Scl-70, centromere, dsDNA, Ro52, Ro60, SS-B, Ribo-P, DFS70, and EJ). In conclusion, this first study on anti-fibrillarin antibodies measured using a novel PMAT assay shows promising results where the new PMAT assay had high level of agreement to FEIA for the detection of anti-fibrillarin antibodies. The availability of novel AFA assays such as PMAT might facilitate the clinical deployment, additional studies, standardization efforts, and potentially consideration of AFA for next generations of the classification criteria.
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http://dx.doi.org/10.1007/s12026-021-09197-1DOI Listing
April 2021

SASH3 variants cause a novel form of X-linked combined immunodeficiency with immune dysregulation.

Blood 2021 Apr 19. Epub 2021 Apr 19.

Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States.

SAM and SH3 domain-containing 3 (SASH3), also called SH3-containing Lymphocyte Protein (SLY1) is a putative adaptor protein that is postulated to play an important role in the organization of signaling complexes and propagation of signal transduction cascades in lymphocytes. The SASH3 gene is located on the X-chromosome. Here, we identified three novel SASH3 deleterious variants in four unrelated male patients with a history of combined immunodeficiency and immune dysregulation manifesting as recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopenias. Patients exhibited CD4+ T cell lymphopenia, decreased T cell proliferation and cell cycle progression, and increased T cell apoptosis in response to mitogens. In vitro T-cell differentiation of CD34+ cells and molecular signatures of rearrangements at the T-cell receptor alpha (TRA) locus were indicative of impaired thymocyte survival. These patients also manifested neutropenia and B and NK cell lymphopenia. Lentivirus-mediated transfer of the SASH3 cDNA corrected protein expression, in vitro proliferation and signaling in SASH3-deficient Jurkat and patient-derived T cells. These findings define a new type of X-linked combined immunodeficiency in humans that recapitulates many of the abnormalities reported in Sly1-/- and Sly1D/Dmutant mice, highlighting an important role of SASH3 in human lymphocyte function and survival.
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http://dx.doi.org/10.1182/blood.2020008629DOI Listing
April 2021

Spectrum of Fibrotic Lung Diseases.

N Engl J Med 2020 12;383(25):2485

University of Florence, Florence, Italy

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http://dx.doi.org/10.1056/NEJMc2031135DOI Listing
December 2020

Complete Absence of CD3γ Protein Expression Is Responsible for Combined Immunodeficiency with Autoimmunity Rather than SCID.

J Clin Immunol 2021 Feb 19;41(2):482-485. Epub 2020 Nov 19.

Laboratory of Clinical Immunology and Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

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http://dx.doi.org/10.1007/s10875-020-00918-zDOI Listing
February 2021

Efficacy and Safety of High-Dose Immunoglobulin-Based Regimen in Statin-Associated Autoimmune Myopathy: A Multi-Center and Multi-Disciplinary Retrospective Study.

J Clin Med 2020 Oct 27;9(11). Epub 2020 Oct 27.

Department of Medicine, Rheumatology Clinic, University of Udine, ASUFC Udine, 33100 Udine, Italy.

Statin-associated autoimmune myopathy is a rare muscle disorder, characterized by autoantibodies against HMGCR. The anti-HMGCR myopathy persists after statin, and often requires immunosuppressive therapy. However, there is not a standardized therapeutic approach. The purpose of this study is to report the effectiveness of the immunosuppressive treatment employed in a multi-center and multi-disciplinary cohort of patients affected by anti-HMGCR myopathy, in which an immunoglobulin (IVIG)-based treatment strategy was applied. We collected 16 consecutive patients with a diagnosis of anti-HMGCR myopathy, between 2012 and 2019, and recorded data on clinical and laboratory presentation (i.e., muscle strength, serum CK levels, and anti-HMGCR antibody titer) and treatment strategies. Our results highlight the safety and efficacy of an induction therapy combining IVIG with GCs and/or methotrexate to achieve persistent remission of the disease and steroid-free maintenance. Under IVIG-based regimens, clinical improvement and CK normalization occurred in more than two thirds of patients by six months. Relapse rate was low (3/16) and 2/3 relapses occurred after treatment suspension. Nearly 90% of the patients who successfully discontinued GCs were treated with a triple immunosuppressive regimen. In conclusion, an IVIG-based regimen, which particularly includes high-dose immunoglobulin, GCs and methotrexate, can provide a fast remission achievement with GC saving.
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http://dx.doi.org/10.3390/jcm9113454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692610PMC
October 2020

Disseminated Mycobacterium xenopi in an Adult with IL-12Rβ1 Deficiency.

J Clin Immunol 2020 11 27;40(8):1166-1170. Epub 2020 Aug 27.

Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, FI, Italy.

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http://dx.doi.org/10.1007/s10875-020-00848-wDOI Listing
November 2020

Autoantibodies to protein-arginine deiminase (PAD) 4 in rheumatoid arthritis: immunological and clinical significance, and potential for precision medicine.

Expert Rev Clin Immunol 2019 10 13;15(10):1073-1087. Epub 2019 Oct 13.

Research and Development, Inova Diagnostics , San Diego , CA , USA.

: The protein-arginine deiminase (PAD) 4 enzyme plays an important role in the pathogenesis of rheumatoid arthritis (RA) and also represents an antigenic target. Anti-PAD4 antibodies can be present in RA and are associated with specific clinical features. : This review aims to analyze the current knowledge and recent findings on anti-PAD4 antibodies in RA and their clinical and immunological significance. : Anti-PAD4 antibodies are not currently used in clinical practice for the management of RA. Nevertheless, there is growing evidence of their relevance in RA, and of their potential utility to improve diagnosis, patient stratification, and prognosis.
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http://dx.doi.org/10.1080/1744666X.2020.1668778DOI Listing
October 2019

Intravenous immunoglobulin therapy: a snapshot for the internist.

Intern Emerg Med 2019 10 15;14(7):1041-1049. Epub 2019 Jul 15.

Experimental and Clinical Medicine Department, University of Firenze, Largo Brambilla 3, 50100, Firenze, Italy.

Intravenous immunoglobulins are the cornerstone for the treatment of primary humoral immunodeficiencies and may be used for a great number of other autoimmune, neurological and hematological conditions as well. Given their wide application, the possibility of running across a patient who needs this kind of therapy is becoming increasingly common. Generally, intravenous immunoglobulins are well tolerated. However, numerous adverse reactions ranging from mild to severe have been reported and linked to patient- and product-related factors. For all these reasons, we present herein a comprehensive review of the on- and off-label applications of intravenous immunoglobulins and provide a guide for the internist how to minimize the risk of adverse reactions and manage them.
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http://dx.doi.org/10.1007/s11739-019-02150-zDOI Listing
October 2019

Belimumab reduces antiphospholipid antibodies in SLE patients independently of hydroxychloroquine treatment.

Autoimmun Rev 2019 03 11;18(3):312-314. Epub 2019 Jan 11.

Department of Experimental and Clinical Medicine, University of Firenze, Italy.

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http://dx.doi.org/10.1016/j.autrev.2018.11.002DOI Listing
March 2019

Omalizumab dampens type 2 inflammation in a group of long-term treated asthma patients and detaches IgE from FcεRI.

Eur J Immunol 2018 12 9;48(12):2005-2014. Epub 2018 Oct 9.

Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, Florence, Italy.

Even if omalizumab is broadly used in the treatment of severe, allergic asthma, the immunological effects in long-term treated patients have not been fully elucidated. To this aim, a cohort of 15 allergic asthmatic patients treated with omalizumab for at least three years was compared with 12 allergic asthma patients treated with standard therapy. Omalizumab treated asthmatic patients showed lower frequencies of circulating plasmacytoid DCs, and lower CD154 expression on CD4 T-helper cells than the control group. Moreover, basophils and DCs from omalizumab-treated patients had lower surface expression of IgE compared to the control group. In a longitudinal evaluation of two patients that started omalizumab treatment, we show that FcεRI free of IgE were evident on basophils just after four weeks of drug administration. Finally, in vitro experiments with basophils obtained from healthy donors confirm that omalizumab is able to detach IgE from high affinity IgE receptors. Collectively these data indicate that long-term omalizumab treatment dampens type 2 inflammation acting on different cell types that play a pivotal role in the pathogenesis of allergic asthma. Moreover, we have identified a further mechanism of action of omalizumab, such as the ability to detach IgE from its receptor.
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http://dx.doi.org/10.1002/eji.201847668DOI Listing
December 2018

Bench to bedside review of myositis autoantibodies.

Clin Mol Allergy 2018 7;16. Epub 2018 Mar 7.

Experimental and Clinical Medicine Department, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.

Idiopathic inflammatory myopathies represent a heterogeneous group of autoimmune diseases with systemic involvement. Even though numerous specific autoantibodies have been recognized, they have not been included, with the only exception of anti-Jo-1, into the 2017 Classification Criteria, thus perpetuating a clinical-serologic gap. The lack of homogeneous grouping based on the antibody profile deeply impacts the diagnostic approach, therapeutic choices and prognostic stratification of these patients. This review is intended to highlight the comprehensive scenario regarding myositis-related autoantibodies, from the molecular characterization and biological significance to target antigens, from the detection tools, with a special focus on immunofluorescence patterns on HEp-2 cells, to their relative prevalence and ethnic diversity, from the clinical presentation to prognosis. If, on the one hand, a notable body of literature is present, on the other data are fragmented, retrospectively based and collected from small case series, so that they do not sufficiently support the decision-making process (i.e. therapeutic approach) into the clinics.
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http://dx.doi.org/10.1186/s12948-018-0084-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840827PMC
March 2018

NADPH Oxidase Deficiency: A Multisystem Approach.

Oxid Med Cell Longev 2017 21;2017:4590127. Epub 2017 Dec 21.

Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.

The immune system is a complex system able to recognize a wide variety of host agents, through different biological processes. For example, controlled changes in the redox state are able to start different pathways in immune cells and are involved in the killing of microbes. The generation and release of ROS in the form of an "oxidative burst" represent the pivotal mechanism by which phagocytic cells are able to destroy pathogens. On the other hand, impaired oxidative balance is also implicated in the pathogenesis of inflammatory complications, which may affect the function of many body systems. NADPH oxidase (NOX) plays a pivotal role in the production of ROS, and the defect of its different subunits leads to the development of chronic granulomatous disease (CGD). The defect of the different NOX subunits in CGD affects different organs. In this context, this review will be focused on the description of the effect of NOX2 deficiency in different body systems. Moreover, we will also focus our attention on the novel insight in the pathogenesis of immunodeficiency and inflammation-related manifestations and on the protective role of NOX2 deficiency against the development of atherosclerosis.
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http://dx.doi.org/10.1155/2017/4590127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753020PMC
August 2018

Reflex testing of speckled cytoplasmic patterns observed in routine ANA HEp-2 indirect immunofluorescence with a multiplex anti-synthetase dot-blot assay: a multicentric pilot study.

Immunol Res 2018 02;66(1):74-78

SOS Immunology and Allergology Laboratory Unit, Department of Laboratory Medicine, Azienda Usl Toscana Centro, S. Giovanni di Dio Hospital, Florence, Italy.

Immunofluorescence on HEp2-cells is the standard diagnostic assay for the detection of anti-nuclear antibodies (ANA). Cytoplasmic speckled patterns are a common finding, and are associated with various antibodies, including anti-synthetase antibodies. However, classic ENA testing generally identifies only anti-Jo-1. Moreover, anti-synthetase syndrome is increasingly recognized as a pleomorphic entity, possibly presenting as isolated arthritis or interstitial lung disease. Sera referred for routine ANA testing were selected on the basis of the presence of a fine dense speckled cytoplasmic pattern (254 samples) and compared to control sera with negative cytoplasm (239 samples). All 493 samples were tested with a commercial synthetase profile dot-blot (D TEK - Alphadia-Alifax) including anti-Jo1, anti-PL7, anti-PL12, anti-EJ, anti-OJ, anti-KS, anti-ZO, anti-HA, anti-SRP, and anti-Ribosome P0. Retrospective clinical data was searched for positive patients. Dot-blot identified 18/254 (7.1%) positive sera in the samples with a cytoplasmic fluorescence pattern and 4/239 (1.7%) in the control group (χ2 = 8.4627; p = 0.003625). Blot intensity was more intense in samples with concordant cytoplasmic staining (cytoplasmic negative 27 ± 12.4; cytoplasmic positive 53.9 27 ± 27.7; p = 0.0027). In the positive samples, 8/18 had a highly compatible diagnosis (myositis, interstitial lung disease, arthritis), 7/18 an uncharacterized connective tissue disease, and 3 a diagnosis not associated with the presence of anti-synthetase antibodies. We evaluated the performance of a dot-blot assay for anti-cytoplasmic antibodies in a serologic cohort presenting a cytoplasmic speckled pattern found during routine ANA testing. This algorithm enabled the identification of a significant quota of patients with rare anti-synthetase antibodies and an incomplete or atypical clinical picture. Reflex testing strategies of speckled cytoplasmic patterns with multiplex assays containing cytoplasm-specific antigens, as opposed to standard ENA testing, may yield important data and for this reason should be implemented in routine ANA testing.
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http://dx.doi.org/10.1007/s12026-017-8974-3DOI Listing
February 2018

Neuromyelitis optica, atypical hemophagocytic lymphohistiocytosis and heterozygous perforin A91V mutation.

J Neuroimmunol 2017 10 15;311:10-13. Epub 2017 Aug 15.

Department of Clinical and Experimental Medicine, Unit of Internal Medicine, University of Florence, Italy.

Neuromyelitis optica is an autoimmune demyelinating inflammatory disease characterized by optic neuritis and myelitis with anti-aquaporin 4 antibodies. Hemophagocytic lymphohistiocytosis is a severe systemic inflammatory syndrome that can present in a genetic primary form or secondarily to infective, neoplastic or autoimmune diseases. Our case discusses the first reported case of atypical late-onset hemophagocytic lymphohistiocytosis in a patient with neuromyelitis optica, with multiple triggering factors and carrying the common A91V hypomorphic perforin mutation, that blurs the distinction between primary and secondary forms.
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http://dx.doi.org/10.1016/j.jneuroim.2017.08.003DOI Listing
October 2017

Allergy and Sexual Behaviours: an Update.

Clin Rev Allergy Immunol 2019 Jun;56(3):269-277

Department of Internal Medicine, Section of Immunoallergology and Respiratory Diseases, University of Florence, Florence, Italy.

The exact prevalence of hypersensitivity reactions related to sexual behaviours is not known; however, they heavily impact on the quality of life and of sex life of affected patients. In fact, not only common respiratory and skin allergies, such as asthma, rhinitis, urticaria and atopic dermatitis, but also food and drug allergy have been found to negatively affect the quality of sex life. Allergic diseases impact on the sexual function in both physical and psychological ways, representing one of the main complaints of a considerable proportion of patients. Sexual behaviours may act as the triggers of allergic reactions or as the carriers of allergens. Food and drug allergens can be carried through human organic fluids, like saliva and semen. Latex in condoms and numerous substances in lubricants, spermicides, topical medications and cosmetics can cause allergic reactions or contact dermatitis. Sexual activity itself is also a potential trigger of symptoms in patients affected by respiratory allergies, like honeymoon asthma and rhinitis. In seminal plasma hypersensitivity, seminal fluid proteins are the culprit allergens. The present review aims at summarizing the state of the art about allergy and sexual behaviours. In clinical practice, the influence of common allergic diseases on the sexual quality of life should be taken carefully into account. Sexual behaviours need to be accounted in the differential diagnosis of hypersensitivity reactions, and awareness on those exposure routes should be raised between different specialists and general practitioners.
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http://dx.doi.org/10.1007/s12016-017-8618-3DOI Listing
June 2019

Anti-HMGCR and anti-DFS70 antibodies immunofluorescence patterns.

Autoimmun Rev 2017 03 12;16(3):321-322. Epub 2017 Jan 12.

Department of Experimental and Clinical Medicine, Immunoallergology Unit, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1016/j.autrev.2017.01.002DOI Listing
March 2017

A case of acute febrile neck pain.

Intern Emerg Med 2017 06 22;12(4):551-552. Epub 2016 Sep 22.

Medical-Geriatric Department, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

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http://dx.doi.org/10.1007/s11739-016-1545-0DOI Listing
June 2017

Tocilizumab-induced mucosal ulcers in a patient with relapsing polychondritis: An adverse drug reaction?

Semin Arthritis Rheum 2016 10 1;46(2):e9-e10. Epub 2016 Apr 1.

Rheumatology Section, Immunoallergology Unit, AOU Careggi, Florence, Italy.

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http://dx.doi.org/10.1016/j.semarthrit.2016.03.016DOI Listing
October 2016

MDA5-positive dermatomyositis: an uncommon entity in Europe with variable clinical presentations.

Clin Mol Allergy 2015 9;13:22. Epub 2015 Nov 9.

Unit of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.

Clinically amyopathic dermatomyositis (CADM), described almost 50 years ago, is defined on the basis of still not validated criteria and characterized by skin findings almost without muscle weakness. Autoantibodies directed against the cytosolic pathogen sensor MDA5 (CADM 140) can mark this subtype of dermatomyositis which has been reported to associate, in particular ethnic groups, with severe progressive interstitial lung disease, poor prognosis and an hyperferritinemic status resembling hemophagocytic-like syndromes. MDA5 may be relevant in that Interferon-signature claimed to characterize inflammatory myopathies and dermatomyosits itself, but its role is not clear. However, the titre of anti-MDA5 autoantibodies seems to correlate with the outcome. In Caucasian populations the association between anti-MDA5 positive CADM and rapidly progressive interstitial lung disease seems to be weaker, but the limited numbers of patients described so far could explain the lack of statistical significance. As a fact, European patients with circulating anti-MDA5 autoantibodies may be clinically inhomogeneous and exhibit different rates of severity. The two patients affected by anti-MDA5 positive dermatomyositis described hereafter provide a clear example of the extreme variability of the disease in terms of laboratory findings and clinical features.
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http://dx.doi.org/10.1186/s12948-015-0031-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637993PMC
November 2015