OBJECTIVES: Identification of factors associated with disease activity and B and T cell activation is a challenge in primary Sjogren's syndrome (pSS). Neurotrophins (NTs), recently reported as B cell antiapoptotic, and T-cell activation factors seem to be implicated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Samples from 18 pSS patients and 12 control subjects were studied to determine serum levels of nerve-growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and their relationships with T- and B-cell activation and disease activity. Peripheral blood mononuclear cells (PBMCs) from patients with pSS and controls were examined by flow cytometry for HLA-DR expression by activated T cells. B cell activation was evaluated by B cell activating factor (BAFF) serum levels measured by enzyme-linked immunosorbent assay (ELISA) and immunoglobulin (Ig) and free light chain (FLC) levels. RESULTS: Mean serum levels of BDNF in pSS patients were significantly higher than in healthy controls and correlated directly with disease activity. NGF levels were associated with the subgroup of patients with hypergammaglobulinaemia. The pSS group was characterized by peripheral CD4+ and CD8+ T cell activation that correlated positively with BDNF and NGF levels, respectively. CONCLUSION: NT levels are potential biomarkers for lymphocyte activation in pSS patients.