scholarly journals Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Maria J. Gutierrez ◽  
Stephen V. Desiderio ◽  
Nae-Yuh Wang ◽  
Erika Darrah ◽  
Laura Cappelli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Serum Protein ◽  
Cell Function ◽  
Systemic Autoimmune Disease ◽  
Secreting Cell ◽  
Soluble Factors ◽  
Antibody Secreting Cell ◽  
Protein Levels ◽  
Increased Risk

Background. Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with immune dysregulation and increased risk of infections. The presence of autoantibodies and immunoglobulin abnormalities indicates B-cell and antibody-secreting cell (ASC) dysfunction. We hypothesize that soluble factors associated with B-cell and ASC activity are decreased in RA patients and that this is linked to higher susceptibility to infections.Methods. Using the Johns Hopkins Arthritis Cohort and Biorepository, we contrasted serum protein levels of soluble factors involved in B-cell activation (CD40, CD40L) and B-cell/ASC homing (CXCL10, CXCL11, and CXCL13) or survival (BAFF, APRIL, TACI, and BCMA) in 10 healthy subjects and 23 adult RA patients (aged 24-65 years). We subdivided RA patients into those with (n=17) and those without infections (n=6) within a 2-year period. In order to reduce the effect of RA treatment, we only included patients receiving methotrexate monotherapy or no RA treatments at baseline. Soluble serum protein levels of B-cell/ASC factors were quantified by multiplex immunoassays.Results. We identified that (1) serum levels of soluble BCMA, APRIL, CD40, and CD40L were significantly decreased in RA patients relative to healthy individuals; (2) serum soluble BCMA, predominantly released by ASC, correlated with serum concentrations of class-switched immunoglobulins, IgG and IgA; and (3) RA patients with a history of infections had significantly lower soluble BCMA levels compared with healthy donors and with RA patients without infections.Conclusions. Our study using soluble factors linked to B-cell/ASC activation and survival suggests that there is a paucity of ASC in a subset of RA patients and that this may be linked to altered antibody production and increased risk of infections. Further delineating the link between ASC and infection susceptibility in RA may optimize disease management and provide novel insights into disease pathogenesis that are susceptible to intervention.

scholarly journals Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

2017 ◽  
Vol 76 (12) ◽  
pp. 2025-2030 ◽  
Author(s):  
Louise K Mercer ◽  
Anne C Regierer ◽  
Xavier Mariette ◽  
William G Dixon ◽  
Eva Baecklund ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
General Population ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Treatment Groups ◽  
Increased Risk

BackgroundLymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes.MethodsPatients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD.ResultsAmong 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population.ConclusionThis large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.

scholarly journals EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production

2017 ◽  
Vol 200 (3) ◽  
pp. 1039-1052 ◽  
Author(s):  
Muyao Guo ◽  
Madeline J. Price ◽  
Dillon G. Patterson ◽  
Benjamin G. Barwick ◽  
Robert R. Haines ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Production ◽  
Cell Metabolism ◽  
Transcriptional Program ◽  
Secreting Cell ◽  
Antibody Secreting Cell

Rheumatoid arthritis—clinical features

2013 ◽  
Author(s):  
Eugen Feist ◽  
Gerd-R. Burmester
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Features ◽  
Clinical Laboratory ◽  
Systemic Disease ◽  
Systemic Autoimmune Disease ◽  
Joint Involvement ◽  
Loss Of Function ◽  
Increased Risk ◽  
Autoantibody Status ◽  
Disease Entities

Rheumatoid arthritis (RA) presents with variable clinical features, making this most frequent chronic systemic autoimmune disease with characteristic joint involvement a diagnostic and therapeutic challenge. This chapter describes in detail the different clinical, laboratory and imaging findings in patients with RA. In addition to the characteristic arthritic involvement, which can lead to severe joint changes with progressive destruction and loss of function, other systemic disease manifestations as well as an increased risk for cardiovascular events and non-Hodgkin's lymphoma with relevance for patients' prognosis are described. Recent approaches to early diagnosis and stratification of patients by predictive factors for a severe course of disease are discussed. These patient profiles include increased inflammatory markers, the presence of autoantibodies, and erosive changes at the time of diagnosis. The novel classification criteria for RA and the significance of autoantibody status, namely seropositivity for antibodies against citrullinated antigens as highly specific diagnostic markers, are highlighted to further promote early differentiation of RA from other arthritic disease entities.

scholarly journals Virus-Specific Antibody Secreting Cell, Memory B-cell, and Sero-Antibody Responses in the Human Influenza Challenge Model

2014 ◽  
Vol 209 (9) ◽  
pp. 1354-1361 ◽  
Author(s):  
Kuan-Ying Arthur Huang ◽  
Chris Ka-Fai Li ◽  
Elizabeth Clutterbuck ◽  
Cecilia Chui ◽  
Tom Wilkinson ◽  
...  
Keyword(s):  
B Cell ◽  
Specific Antibody ◽  
Antibody Responses ◽  
Human Influenza ◽  
Secreting Cell ◽  
Cell Memory ◽  
Memory B Cell ◽  
Antibody Secreting Cell ◽  
Virus Specific Antibody

B-cell lymphoma of the larynx in a patient with rheumatoid arthritis

2005 ◽  
Vol 119 (8) ◽  
pp. 646-648 ◽  
Author(s):  
S Patiar ◽  
J D Ramsden ◽  
A P Freeland
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Arthritis Patient ◽  
B Cell ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Primary Site ◽  
Hodgkin's Lymphoma ◽  
Increased Risk ◽  
Previously Treated

We report a case of B-cell lymphoma with the larynx as the primary site of presentation in a rheumatoid arthritis patient previously treated with methotrexate. Primary non-Hodgkin’s lymphoma (NHL) of the larynx is rare. There may be an increased risk of lymphoma in patients with rheumatoid arthritis, with an even higher risk in those patients treated with methotrexate. The diagnostic and treatment options are discussed.

scholarly journals Potential protection against type 2 diabetes in obesity through lower CD36 expression and improved exocytosis in β-cells

2020 ◽  
Author(s):  
Ada Admin ◽  
Mototsugu Nagao ◽  
Jonathan L.S. Esguerra ◽  
Akira Asai ◽  
Jones K. Ofori ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
B Cell ◽  
Cell Function ◽  
Antibody Treatment ◽  
Protein Levels ◽  
Cd36 Expression ◽  
Irs Proteins ◽  
Human B Cell

<div>Obesity is a risk factor for type 2 diabetes (T2D), however not all obese individuals develop the disease. In this study, we aimed to investigate the cause of differential insulin secretion capacity of pancreatic islets from T2D and non-T2D (ND) especially obese donors (BMI ≥30 kg/m2). Islets from obese T2D donors had reduced insulin secretion, decreased B-cell exocytosis and higher expression of fatty acid translocase CD36. We tested the hypothesis that CD36 is a key molecule in the reduced insulin secretion capacity. Indeed, CD36 overexpression led to decreased insulin secretion, impaired exocytosis and reduced granule docking. This was accompanied with reduced expression of the exocytotic proteins, SNAP25, STXBP1 and VAMP2, likely because CD36 induced down-regulation of the IRS proteins, suppressed insulin signaling PI3K-AKT pathway and increased nuclear localization of the transcription factor FoxO1. CD36 antibody treatment of the human B-cell line, EndoC-BH1, increased IRS1 and exocytotic protein levels, improved granule docking and enhanced insulin secretion. Our results demonstrate that B-cells from obese T2D donors have dysfunctional exocytosis likely due to an abnormal lipid handling represented by differential CD36 expression. Hence, CD36 could be a key molecule to limit B-cell function in T2D associated with obesity. <br></div><div> </div>

scholarly journals Defective T-Cell Apoptosis and T-Regulatory Cell Dysfunction in Rheumatoid Arthritis

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 223 ◽  
Author(s):  
Charles Malemud
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Treg Cell ◽  
Cell Function ◽  
Clinical Symptoms ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Systemic Autoimmune Disease ◽  
Apoptosis Resistance ◽  
Cell Dysfunction

Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease that mostly affects small and large synovial joints. At the molecular level, RA is characterized by a profoundly defective innate and adaptive immune response that results in a chronic state of inflammation. Two of the most significant alterations in T-lymphocyte (T-cell) dysfunction in RA is the perpetual activation of T-cells that result in an abnormal proliferation state which also stimulate the proliferation of fibroblasts within the joint synovial tissue. This event results in what we have termed “apoptosis resistance”, which we believe is the leading cause of aberrant cell survival in RA. Finding therapies that will induce apoptosis under these conditions is one of the current goals of drug discovery. Over the past several years, a number of T-cell subsets have been identified. One of these T-cell subsets are the T-regulatory (Treg) cells. Under normal conditions Treg cells dictate the state of immune tolerance. However, in RA, the function of Treg cells become compromised resulting in Treg cell dysfunction. It has now been shown that several of the drugs employed in the medical therapy of RA can partially restore Treg cell function, which has also been associated with amelioration of the clinical symptoms of RA.

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