Background/Purpose: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease with an incompletely understood pathogenesis and heterogenous disease manifestations. Identifying cellular immune changes that may predict disease severity could lead to identification of biomarkers and potential targets for therapy. We examined a cohort of pSS patients to identify the cellular immunologic features significantly associated with disease activity, as measured by the EULAR Sjögren’s syndrome disease activity index (ESSDAI) and the focus score on minor salivary gland (MSG) biopsy.

Methods: 35 participants who met the ACR 2016 classification criteria for pSS were recruited. Peripheral blood cellular immunological changes were assessed by flow cytometry and transcript levels of BAFF, interferon (IFN)-induced and plasma cell-expressed genes were quantified by NanoString. Normalized Log₂ transformed expression levels of 5 IFN-induced genes were summed to generate the IFN5 score. Associations between the ESSDAI, focus score, and cellular immunological changes were evaluated using Spearman’s correlation coefficient.

Results: The ESSDAI was significantly correlated with the focus score (r=0.64, p< 0.01).  The majority of T and B cell populations, including the proportions of naïve, class-switched memory, un-switched memory, and CD27^– memory B cells and their activation, as well as IFN-γ-, IL-17-, or IL-21-producing T cells, did not correlate with either measure of disease activity.  However, the proportion of transitional B cells (CD27^–IgD⁺CD24^hiCD38^hi; r=0.40, p=0.03) and proportion of activated memory T follicular helper cells (CXCR5⁺PD1^hi) in the CD4⁺ T cell compartment (r=0.39, p=0.05) and CD3⁺ T cell compartment (r=0.42, p=0.04) were significantly associated with the focus score. In addition, the frequency of T regulatory cells (CD4⁺FOXP3⁺HELIOS⁺) was positively correlated with the ESSDAI (r=0.61, p=0.04).  Type I IFN-induced gene expression, as measured by the IFN5 score, was significantly associated with both focus score (r=0.37, p=0.05) and ESSDAI (r=0.37, p=0.04).

Conclusion: The findings suggest that elevated levels of IFN-induced gene expression and increased proportions of T follicular helper cells are potential biomarkers of increased disease activity and may constitute good targets for disease treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-and-t-cell-immunologic-features-associated-with-higher-disease-activity-score-and-focus-score-in-primary-sjogren-syndrome/