Association of Circulating Antibody‐Secreting Cell Maturity With Disease Features in Primary Sjögren's Syndrome

Abstract

Objective B cell hyperactivity plays an important role in primary Sjögren's syndrome (SS). We undertook this study to better understand the B cell effector branch, namely antibody‐secreting cells (ASCs) in primary SS, and to examine the quantity, maturity, and inflammatory properties of ASCs in primary SS patients. Methods Circulating ASCs, defined as CD3–CD14–CD27+CD38++ cells, from 21 primary SS patients and 10 healthy controls were assessed using spectral flow cytometry. Expression levels of relevant ASC markers relating to maturity, survival, and inflammatory status were analyzed using a t‐distributed stochastic neighbor embedding approach. Correlation of ASC properties with primary SS disease parameters was assessed. Results ASCs were more abundant in peripheral blood from primary SS patients than from healthy controls (mean ± SD 3.1 ± 5.1 cells/μl versus 1.1 ± 1.0 cells/μl, respectively; P = 0.048) and displayed a more mature phenotype (mean ± SD CD19– ASCs 0.37 ± 1.21 cells/μl versus 0.06 ± 0.11 cells/μl, respectively; P = 0.005). An inflammatory CXCR3+ phenotype of ASCs correlated positively with our newly developed ASC maturity index (r = 0.568, P = 0.007) but correlated negatively with antiinflammatory interleukin‐10 expression (r = –0.769, P < 0.001). ASCs with a higher maturity index also demonstrated higher levels of the pro‐survival protein myeloid cell leukemia 1 (r = 0.567, P = 0.007). Frequency and/or maturity of ASCs correlated with several primary SS disease parameters, such as antinuclear antibody and anti‐La/SSB titers, salivary gland focus scores, and ocular staining scores. Conclusion Quantity and maturity of ASCs in primary SS patients are increased and correlate with disease parameters. A higher maturity index of ASCs marks a pro‐survival and proinflammatory phenotype. Altogether, B cell hyperactivity in primary SS extends to the peripheral ASC compartment, raising potential for ASCs as future biomarkers or targets for primary SS treatment.

Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development

“…7). Increased CD138 + plasma cells are a hallmark of several chronic AID [85,86] and both MuSK MG and pemphigus likely fit the same classification. Why the other AID did not show increased mature plasma cell numbers is not known.…”

Targeting BMI‐1 to deplete antibody‐secreting cells in autoimmunity

“…Therefore, we established an ex vivo assay to assess the survival of human ASCs sort-purified from human peripheral blood mononuclear cells (PBMC) obtained from Sj€ ogren's syndrome patients. ASCs are increased in the peripheral blood of Sj€ ogren's syndrome compared to healthy controls 33,34 and this is correlated with disease severity, potentially indicating a higher prevalence of autoreactive ASCs. 34 The Sj€ ogren's syndrome patients who participated in this study had a range of comorbidities, serum IgG concentrations, and disease severity (Supplementary table 1).…”

“…ASCs are increased in the peripheral blood of Sj€ ogren's syndrome compared to healthy controls 33,34 and this is correlated with disease severity, potentially indicating a higher prevalence of autoreactive ASCs. 34 The Sj€ ogren's syndrome patients who participated in this study had a range of comorbidities, serum IgG concentrations, and disease severity (Supplementary table 1). All patients were positive for antibodies against SSA/Ro, a key autoantigen in Sj€ ogren's syndrome.…”