Background/Purpose: CXCR5 is a chemokine receptor expressed on B and T cell subsets, which binds the CXCL13 ligand produced by follicular dendritic cells. It is involved in cell migration and germinal centre reactions. The latter is observed ectopically in the salivary gland (SG) target organ of the rheumatic autoimmune disease primary Sjögren’s syndrome (pSS). Further, genome-wide association studies have linked polymorphisms of CXCR5 to pSS, making the pathway important to explore for identification of novel treatment targets and for understanding disease pathogenesis. In this study we aimed to investigate the expression of CXCR5 in the peripheral blood and minor SG biopsies of pSS patients.

Methods: Flow cytometry was performed for cell populations and activation markers on PBMCs acquired from 14 untreated pSS patients, 10 pSS patients treated with the antimalarial drug hydroxychloroquine, and 15 sex and age matched healthy controls. Moreover, minor paraffin-embedded SG biopsies from the same pSS patients were stained for the detection of CXCR5+ cells using immunohistochemistry.

Results: HLA-DR expression was significantly increased in the untreated pSS patients compared to controls, on both CD19+ B cells (P <0.04) and CD14+ monocytes (P <0.001), with a significant decrease in expression following treatment on both CD19+ B cells and monocytes (P <0.009). A trend towards a decreased percentage of CXCR5+ cells as well as CXCR5 cell surface expression was observed for most B and T cell subsets in untreated patients with pSS, reaching statistical significance in CD19+CD27+IgD+ marginal zone (P <0.001) and CD19+CD27+IgD- memory (P <0.006) B cells as well as in CD3+CD4+CCR6+ Th17 cells (P <0.03). These observations were not reversed, but rather aggravated by hydroxychloroquine treatment. Meanwhile, immunohistochemical staining of SG biopsies revealed high numbers of CXCR5+ cells both within the focal infiltrates and interstitially in the target organ of these patients.

Conclusion: We conclude that the decrease of CXCR5 levels in the periphery of patients with Sjögren’s syndrome result from homing of B and T cells to the autoimmune target organs. Hydroxychloroquine treatment appears not to be efficient in inhibiting the factors driving the trafficking, although it decreases the MHC class II expression. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in pSS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-the-chemokine-receptor-cxcr5-is-decreased-in-the-periphery-of-patients-with-primary-sjogrens-syndrome/