B Cells Drive Lung Fibrosis and Systemic Autoimmune Disease in Experimental Systemic Sclerosis.

2009 ◽  
Author(s):  
TA Delaney ◽  
J Kearley ◽  
C Chen ◽  
E Benjamin ◽  
R Herbst ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
B Cells ◽  
Autoimmune Disease ◽  
Lung Fibrosis ◽  
Systemic Autoimmune Disease

scholarly journals Constitutive expression of bcl-2 in B cells causes a lethal form of lupuslike autoimmune disease after induction of neonatal tolerance to H-2b alloantigens.

1996 ◽  
Vol 183 (6) ◽  
pp. 2523-2531 ◽  
Author(s):  
M López-Hoyos ◽  
R Carrió ◽  
R Merino ◽  
L Buelta ◽  
S Izui ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Disease ◽  
Constitutive Expression ◽  
Systemic Autoimmune Disease ◽  
Spleen Cells ◽  
Term Survival ◽  
F1 Hybrid ◽  
Wide Range

The bcl-2 protooncogene has been shown to provide a survival signal to self-reactive B cells, but it fails to override their developmental arrest after encounter with antigen. Furthermore, constitutive expression of bcl-2 in B cells does not promote the development of autoimmune disease in most strains of mice, indicating that signals other than those conferred by bcl-2 are required for long-term survival and differentiation of self-reactive B cells in vivo. To further examine the factors that are required for the pathogenesis of autoimmune disease, we have assessed the effect of bcl-2 overexpression on the development of host-versus-graft disease, a self-limited model of systemic autoimmune disease. In this model, injection of spleen cells from (C57BL/6 x BALB/c)F1 hybrid mice into BALB/c newborn parental mice induces immunological tolerance to donor tissues and activation of autoreactive F1 donor B cells through interactions provided by allogeneic host CD4+ T cells. BALB/c newborns injected with spleen cells from (C57BL/6 x BALB/c)F1 mice expressing a bcl-2 transgene in B cells developed high levels of anti-single-stranded DNA and a wide range of pathogenic autoantibodies that were not or barely detectable in mice injected with nontransgenic spleen cells. In mice injected with transgenic B cells, the levels of pathogenic autoantibodies remained high during the course of the study and were associated with long-term persistence of donor B cells, development of a severe autoimmune disease, and accelerated mortality. These results demonstrate that bcl-2 can provide survival signals for the maintenance and differentiation of autoreactive B cells, and suggest that both increased B cell survival and T cell help play critical roles in the development of certain forms of systemic autoimmune disease.

scholarly journals Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Takemichi Fukasawa ◽  
Ayumi Yoshizaki ◽  
Satoshi Ebata ◽  
Asako Yoshizaki-Ogawa ◽  
Yoshihide Asano ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
B Cells ◽  
Autoimmune Disease ◽  
Single Cell ◽  
Topoisomerase I ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Single Cell Level ◽  
Cell Level ◽  
Inflammatory Cytokine Production

Despite antigen affinity of B cells varying from cell to cell, functional analyses of antigen-reactive B cells on individual B cells are missing due to technical difficulties. Especially in the field of autoimmune diseases, promising pathogenic B cells have not been adequately studied to date because of its rarity. In this study, functions of autoantigen-reactive B cells in autoimmune disease were analyzed at the single-cell level. Since topoisomerase I is a distinct autoantigen, we targeted systemic sclerosis as autoimmune disease. Decreased and increased affinities for topoisomerase I of topoisomerase I-reactive B cells led to anti-inflammatory and pro-inflammatory cytokine production associated with the inhibition and development of fibrosis, which is the major symptom of systemic sclerosis. Furthermore, inhibition of pro-inflammatory cytokine production and increased affinity of topoisomerase I-reactive B cells suppressed fibrosis. These results indicate that autoantigen-reactive B cells contribute to the disease manifestations in autoimmune disease through their antigen affinity.

scholarly journals Systemic Autoimmune Disease Caused by Autoreactive B Cells That Receive Chronic Help from Ig V Region-Specific T Cells

2005 ◽  
Vol 175 (4) ◽  
pp. 2391-2400 ◽  
Author(s):  
Ludvig André Munthe ◽  
Alexandre Corthay ◽  
Audun Os ◽  
Michael Zangani ◽  
Bjarne Bogen
Keyword(s):  
T Cells ◽  
B Cells ◽  
Autoimmune Disease ◽  
Systemic Autoimmune Disease ◽  
Autoreactive B Cells ◽  
V Region

No Zinc Deficiency But a Putative Immunosuppressive Role for Labile Zn in Patients with Systemic Autoimmune Disease

2017 ◽  
Vol 13 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Johannes Nossent ◽  
Sue Lester ◽  
Maureen Rischmueller ◽  
Peter Zalewski
Keyword(s):  
Autoimmune Disease ◽  
Zinc Deficiency ◽  
Systemic Autoimmune Disease

The involvement of leucine-rich α-2 glycoprotein in the progression of skin and lung fibrosis in bleomycin-induced systemic sclerosis model

2021 ◽  
pp. 1-10
Author(s):  
Hideki Nakajima ◽  
Kimiko Nakajima ◽  
Satoshi Serada ◽  
Minoru Fujimoto ◽  
Tetsuji Naka ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Fibrosis

scholarly journals AB0691 ANALYSIS OF SARS-COV-2 ANTIBODIES IN NON-COVID-19 PATIENTS: COMPARISON BETWEEN SYSTEMIC SCLEROSIS PATIENTS AND HEALTHY CONTROLS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1379.1-1379
Author(s):  
L. Giardullo ◽  
C. Rotondo ◽  
A. Corrado ◽  
N. Maruotti ◽  
R. Colia ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
Reverse Transcriptase ◽  
Real Time ◽  
Polymerase Chain Reaction Assay ◽  
Nuclear Antigen ◽  
Healthy Controls ◽  
Chain Reaction ◽  
Polymerase Chain

Background:Previous study evidenced a cross-reactivity between Sars-Cov-2 antibodies and autoimmune tissue antigen involved in connective tissue diseases, as nuclear antigen (NA), extractable nuclear antigen (ENA), histone and collagen (1). No study has been published about the titer of Sars-Cov-2 antibodies in non-infected patients with autoimmune disease.Objectives:To evaluate the titer of SARS-CoV-2 antibodies in non-COVID-19 patients and compare it between systemic sclerosis (SSc) patients and healthy controls (HC).Methods:A total of 58 patients with SSc (who fulfilled ACR/EULAR 2013 SSc classification criteria) and 18 HC were enrolled. Sera of all participants were collected, and SARS-CoV-2 antibodies (IgG and IgM) were evaluated by means ELISA. In all participants swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were reported negative. Demographic, clinical, and autoimmune serological characteristics of SSc patients were recorded. The normal distribution was assessed using the Shapiro–Wilk’s test. Exclusion criteria was previous or actual Sars-Cov-2 infection. Comparisons between study groups of patients were evaluated by the Student’s t-test or Mann – Whitney U-test as appropriate. The differences between categorial variables were assessed by Pearson chi-square or Fisher’s exact test, as opportune. Statistical significance was set at p ≤ 0.05.Results:We observed significant differences between SSc patients and HC in serum levels of Sars-Cov-2 antibodies (IgG: 1,4±2,1 AU/ml vs 0,36±0,19 AU/ml respectively (p=0,001); and IgM: 2,5±3,1 AU/ml vs 0,8±0,7 AU/ml (p=0,022)). In 5 SSc patients was found titer of Sars-Cov-2 antibodies (IgG) exceeding the cut-off, but the control of swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were negative. No significative differences in Sars-Cov-2 autoantibodies titer were found in subgroup of SSc patients with or without ILD or PAH, limited or diffuse skin subset, and different autoantibodies profile. Furthermore, antibodies titer was not associated with different drugs (steroid, methotrexate, mofetil-mycophenolate and bosentan) in use.Conclusion:A cross mimicking between Sars-Cov-2 antibodies and antinuclear antibodies or anti ENA could be hypothesized. Further studies are necessary to unravel the reliability of Sars-Cov-2 antibodies detection in autoimmune disease.References:[1]Vojdani, A., Vojdani, E., & Kharrazian, D. (2021). Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Frontiers in Immunology, 11, 3679Disclosure of Interests:None declared

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