Interferon-regulated serum biomarkers in primary Sjögren's syndrome

Objectives: Using microarray technology, we previously identified a group of upregulated interferon (IFN)-inducible mRNA transcripts in peripheral blood of well-characterized primary Sjögren's syndrome (pSS) patients. These transcripts were positively correlated with titers of anti-Ro/SSA and anti-La/SSB autoantibodies. The objective of this study was to identify serum protein biomarkers in pSS indicative of upregulated IFN-inducible mRNAs. Methods: Using a composite score to indicate gene expression levels for IFN-inducible mRNA trancripts, we selected 13 pSS patients with high expression levels (IFN-hi) and 13 pSS patients with low levels (IFN-lo) for comparison with 13 age-gender-ethnicity matched healthy controls. The serum levels of 5 interferon-regulated chemokines (I-TAC, IP-10, MCP-1, MIP-1α, and MIP-1β) were measured in duplicate using a multiplex particle-based flow cytometric assay. A composite IFN-protein score was also derived for each subject using normalized levels of these chemokines. Group differences of analyte levels were tested using the Mann-Whitney U test. Spearman's correlation coefficients were calculated for analyte levels versus titers of anti-Ro/SSA and anti-La/SSB autoantibodies. Results: Of the 5 analytes tested, levels of I-TAC, IP-10 and MIP-1α were significantly higher in the IFN-hi group compared to controls (p<0.05), consistent with previous studies showing upregulation of I-TAC and IP-10 in salivary gland specimens. Statistically significant differences were not found between IFN-lo and control, or IFN-hi and IFN-lo groups. Interestingly, the IFN-protein score correlated positively with IFN-gene score (r=.447, p<0.05). IFN-protein scores of pSS patients correlated positively with both anti-Ro/SSA and anti-La/SSB autoantibody levels (r=.473, p<0.05; r=.457, p<0.05, respectively). Conclusions: IFN-regulated serum proteins are present at elevated levels in pSS patients with upregulated IFN-inducible gene expression levels, and are positively correlated with titers of anti-Ro/SSA and anti-La/SSB autoantibodies. This study indicates that I-TAC, IP-10 are promising candidate serum biomarkers for IFN pathway disregulated in pSS. This study was supported by the NIH/NIAMS Grant No. R01AR050782.