Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis
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 fa...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/3658215 |
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| author | Maria J. Gutierrez Stephen V. Desiderio Nae-Yuh Wang Erika Darrah Laura Cappelli Gustavo Nino Michelle Jones Clifton O. Bingham |
| author_facet | Maria J. Gutierrez Stephen V. Desiderio Nae-Yuh Wang Erika Darrah Laura Cappelli Gustavo Nino Michelle Jones Clifton O. Bingham |
| author_sort | Maria J. Gutierrez |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fcc53763d3c549959d89611b4be0c7ed |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-fcc53763d3c549959d89611b4be0c7ed2025-02-03T06:07:46ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/36582153658215Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid ArthritisMaria J. Gutierrez0Stephen V. Desiderio1Nae-Yuh Wang2Erika Darrah3Laura Cappelli4Gustavo Nino5Michelle Jones6Clifton O. Bingham7Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Pulmonary and Sleep Medicine, Children’s National Medical Center, Washington, DC, USADivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USABackground. 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.http://dx.doi.org/10.1155/2019/3658215 |
| spellingShingle | Maria J. Gutierrez Stephen V. Desiderio Nae-Yuh Wang Erika Darrah Laura Cappelli Gustavo Nino Michelle Jones Clifton O. Bingham Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis Journal of Immunology Research |
| title | Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis |
| title_full | Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis |
| title_fullStr | Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis |
| title_full_unstemmed | Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis |
| title_short | Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis |
| title_sort | soluble markers of antibody secreting cell function as predictors of infection risk in rheumatoid arthritis |
| url | http://dx.doi.org/10.1155/2019/3658215 |
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