Serum Th1/Th2 cytokines and clinical characteristics in primary Sjögren's syndrome

Objectives: Cytokines are thought to play an important role in the pathogenesis of primary Sjögren's syndrome (pSS) by promoting cellular and humoral autoimmune processes. The role of key Th1 and Th2 cytokines in pSS have been reported, but their mixed or polarized effect is still a matter of debate.  The aim of the present study was to identify clinically significant Th1 and Th2 cytokines in serum of pSS patients. Methods: Serum samples were collected from a cohort of 20 well-characterized pSS patients and 20 age-gender-ethnicity matched healthy controls. The levels of 29 serum analytes, containing both Th1 and Th2 cytokines, were measured in duplicate using the LincoPlex Human Cytokine 29-Plex Panel (Millipore, St. Charles, MO) coupled with Luminex xMAP technology (Luminex, Austin, TX). Mean cytokine levels between groups were compared using Mann-Whitney U tests. A ‘cytokine score' was calculated for each subject using normalized levels of Th1 and Th2 cytokines that were statistically significant.  Correlations between the composite scores and clinical and laboratory variables were examined using Spearman's tests. Results: Of the 29 analytes tested, levels of 15 (IL-1a, IL-1b, IL-2, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, GM-CSF, IFN-g, IP-10, MIP-1a, TGF-a and TNF-a) were significantly higher in pSS patients compared to healthy controls (p<0.05), and included largely Th1 cytokines. The composite scores calculated from these cytokines correlated negatively with unstimulated whole saliva flow,  tear flow determined by Schirmer's test and total lymphocyte count (r= -.480, p<0.01; r= -.509, p<0.01, r= -.356, p<0.05, respectively), but positively with anti-Ro/SSA autoantibody, erythrocyte sedimentation rate, antinuclear antibody and immunoglobulin A (r=.498, p<0.01; r=.287, p<0.05, r=.374, p<0.05, r=.308, p<0.05, respectively). Conclusions: Our results suggest that a Th1 pattern of immune response characteristic of cellular immunity is predominant in pSS.  The multiplexed cytokine array system holds significant promise to differentiate pSS patients from healthy individuals. This study was supported by the NIH/NIAMS Grant No. R01AR050782.