Foxp3+ T-regulatory Cells in Sjogren's Syndrome: Correlation with the Grade of the Autoimmune Lesion and Certain Adverse Prognostic Factors

Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations, including lymphoma development. To investigate the potential implication of Foxp3(+) T-regulatory cells in the regulation of SS inflammatory responses, we studied their incidence in the minor salivary glands (MSGs) and their relationship with histopathological and clinical disease parameters. Similar percentages of infiltrating Foxp3(+) cells were observed in the MSG lesions of all SS patients (n = 30) and non-SS sialadenitis controls (n = 7). Foxp3(+) cells were not detected in sicca-complaining controls with negative biopsy (n = 6). In SS patients, Foxp3(+) cell frequency varied according to lesion severity, with the highest and lowest frequencies obtained in intermediate and mild MSG lesions, respectively. In the peripheral blood of these patients, reverse distribution of Foxp3(+) cells was observed. Furthermore, the frequency of Foxp3(+) cells in the MSG lesions and peripheral blood was negatively associated (r = -0.6679, P = 0.0065). MSG-infiltrating Foxp3(+) cells were found to positively correlate with biopsy focus score (P = 0.05), infiltrating mononuclear cells, dendritic cells, and macrophages (P </= 0.024 each), and serum C4 levels (P = 0.0328), whereas lower Foxp3(+) cell incidence correlated with adverse predictors for lymphoma development, such as the presence of C4 hypocomplementemia (P = 0.012) and SG enlargement (tendency, P = 0.067). Our findings suggest that the Foxp3(+) T-regulatory cell frequency in the MSG lesions of SS patients correlates with inflammation grade and certain risk factors for lymphoma development.