Evaluation of Histologic, Serologic, and Clinical Changes in Response to Abatacept Treatment of Primary Sjögren's Syndrome: A Pilot Study

Objective To prospectively evaluate histopathologic, blood cellular, serologic, and clinical changes in response to abatacept treatment in patients with primary Sjogren's syndrome (SS). Methods Blood, saliva, and minor salivary gland biopsy samples were obtained before and after the last of 8 doses of abatacept in 11 primary SS patients. The histologic data evaluated the numbers of lymphocytic foci and B and T cell subtypes (CD20+, CD3+, CD4+, and CD8+). The numbers of FoxP3+ regulatory T cells were measured and the FoxP3:CD3 ratio was calculated. Histologic data were compared with results from peripheral blood and with changes in saliva secretion. Results The numbers of lymphocytic foci decreased significantly (P = 0.041). Numbers of local FoxP3+ T cells decreased significantly in percentage of total lymphocytic infiltrates (P = 0.037). In the peripheral blood, B cells increased (P = 0.038). This was due to an expansion of the naive B cell pool (P = 0.034). When adjusting for disease duration, an increase was also noted for total lymphocytes (P = 0.044) and for CD4 cells (P = 0.009). Gamma globulins decreased significantly (P = 0.005), but IgG reduction did not reach significance. Adjusted for disease duration, saliva production increased significantly (P = 0.029). Conclusion CTLA-4Ig treatment significantly reduces glandular inflammation in primary SS, induces several cellular changes, and increases saliva production. Remarkably, this increase in saliva production is significantly influenced by disease duration.