Interferon-regulated serum biomarkers of primary Sjogren's syndrome.

摘要

Primary Sjogren's syndrome (pSS) is a chronic disabling disorder affecting a substantial proportion of the general population. Clinical manifestations are heterogeneous and can be severe or life-threatening. Currently, no specific tests are available for diagnosis of pSS. Therapies are limited and clinical management can be challenging. The precise etiology is unknown and our understanding of pSS remains descriptive and incomplete. Development of novel disease markers readily detectable in serum should alleviate the significant diagnostic, prognostic, and therapeutic challenges associated with pSS.;Recently, we used gene expression microarrays to discover a group of type I interferon (IFN)-regulated mRNA transcripts that are expressed at elevated levels in the peripheral blood of pSS patients. Interestingly, this IFN signature was correlated with important clinical and laboratory parameters such as whole unstimulated saliva flow, tear flow determined by the Schirmer's test and serological titers of autoantibodies (anti-Ro/SSA and anti-La/SSB). In an effort to build upon our gene expression studies, we have utilized a multiplex fluorescent bead-based immunoassay to identify protein biomarkers in serum of pSS patients. We identified elevated levels of certain type I IFN-regulated chemokines in serum of pSS patients bearing an IFN-gene expression signature. Interestingly, both genes and proteins (chemokines) were highly correlated. These chemokines were also correlated with important clinical and laboratory measures of pSS.;We then validated the significant chemokines in serum collected from an independent cohort of pSS patients using the same immunoassay. The chemokine levels continued to be correlated with important clinical and laboratory measures. Our studies have identified IFN-regulated chemokines as promising biomarkers for pSS. These findings also suggest that IFN-related pathways have potential as relevant therapeutic targets for this devastating disease.