Advances in Understanding, Diagnosing, and Treating Sjogren Syndrome

Robert I. Fox, MD, PhD


July 31, 2015

In This Article

More on SS Biomarkers

Given the challenges in both diagnosis and treatment of SS, a substantial body of research presented focused on identifying biomarkers for both prognosis and diagnosis.[25,26,27] Specifically, bioinformatic methods were used to identify changes in proteomic alterations in saliva and tears, and new markers from the gene ontology database were identified and correlated with clinical features. Peluso and colleagues[26] reported that isoforms of the calcium-binding S100 protein family, which induce a proinflammatory response, were upregulated in the saliva and tears of patients with SS. Bologna and colleagues[27] reported a preliminary proteomic analysis of saliva in patients with SS, finding proteins associated with acute and chronic inflammation, suggesting that clinical changes in the salivary glands might correlate with an altered salivary proteome. Another proteomic analysis of saliva found that depletion of certain high-abundance proteins and upregulation or posttranslational modifications by glycosylation may provide useful outcome markers in therapeutic trials.[29] Larssen and colleagues[29] noted alteration of the levels of several proteins in the cerebrospinal fluid (CSF) of patients with SS and severe fatigue, which represented one of the first reports of objective CSF changes associated with fatigue and systemic autoimmune disease. Further characterization of these proteins and their function may lead to new therapies.

Gallo and colleagues[30] presented data on alteration in microRNA in salivary glands and the correlation with salivary flow rates. Of 754 microRNAs evaluated, 285 were upregulated and 25 were downregulated, and these changes correlated with the severity of decrease of the salivary flow rate. As with data on other biomarkers, the prognostic significance of these changes will need to be evaluated over longer follow-up and in the context of measuring response to treatment. Papas and colleagues[31] reported significant changes in the oral flora of patients with SS and have begun using bioinformatics tools to identify microbial biomarkers. De Paiva and colleagues[32] reported similar types of alterations in the ocular surface and termed the alterations "mucosal dysbiosis." These studies are consistent with alterations in flora in other diseases and add to the growing body of evidence that interactions between the immune system and endogenous flora have an important role in pathogenesis and end organ damage.

In a small case-control study from Brazil, Balarini and colleagues[33] reported that patients with SS have significantly greater odds (odds ratio, 15.4) of carotid atherosclerotic plaque even after controlling for traditional cardiovascular disease risk factors. They also found correlation with antibodies to carbamylated proteins, calprotein, and circulating levels of tumor necrosis factor (TNF)-R2. Sheppard and colleagues[34] reported on seropositivity to "novel biomarkers": anti-salivary gland protein (SP1), anti-parotid secretory protein (PSP), and anti-carbonic anhydrase (CA6). Among 2306 patients with idiopathic dry eye disease, 26.0% were positive for at least one novel biomarker, and 13.2% of samples were positive for "classic biomarkers," such as SS-A or RF. However, the risk of developing SS if one of these novel biomarkers is positive is not known. With regard to the classic biomarkers, we should be cautious about jumping to conclusions and inducing anxiety in patients because the risk of developing SS in the presence of positive SS-A antibodies is, as previously mentioned, 18%-25%.[13]


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