CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Cristiano Alessandri, Francesco Ciccia, Roberta Priori, Elisa Astorri, Giuliana Guggino, Riccardo Alessandro, Aroldo Rizzo, Fabrizio Conti, Antonina Minniti, Cristiana Barbati, Marta Vomero, Monica Pendolino, Annacarla Finucci, Elena Ortona, Tania Colasanti, Marina Pierdominici, Walter Malorni, Giovanni Triolo, Guido Valesini

Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome and/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Our study provides evidence for the first time that autophagy is upregulated in CD4(+) T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. These findings suggest that CD4(+) T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS.