In patients with primary Sjogren syndrome (pSS), 3 separate biomarkers related to B-cell activity, including B-cell activating factor (BAFF), β-2 microglobulin (β2M), and serum free light chains (FLCs), were associated with various domains of the European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI), according to findings published in Rheumatology.
Data show that patients with pSS have elevations in these disease markers, which are known to correlate with overall disease activity. However, to date there has been little research into the associations between such biomarkers and individual, system-specific activity. Investigators sought to examine these relationships using the 12 domains of the ESSDAI to make important distinctions regarding pathogenesis and systemic manifestations of pSS.
Serum measurements from participants in the UK Primary Sjogren’s Syndrome Registry Biobank (n=553; 95.1% women; 93.7% Caucasian; mean age, 59.1 years) were analyzed for BAFF, β2M, and FLC levels and were compared with serum measurements from healthy control patients (n=286; 90.9% women; 88.1% Caucasian; mean age, 48.0 years). Patients were assessed for total and domain scores on the ESSDAI and the clinical ESSDAI (ClinESSDAI). The ClinESSDAI, which consists of the ESSDAI without the biological domain, was used to control for confounding.
Patients with pSS had higher levels of all 3 biomarkers compared with control patients, with significant associations between biomarker levels and total ESSDAI and ClinESSDAI scores (P <.001 in all cases). Data show that β2M and FLC were strongly correlated (r=0.75; P <.001), BAFF and FLC were weakly correlated (r=0.11; P <.001), and BAFF and β2M were moderately correlated (r=0.39; P <.001). BAFF was also associated with the peripheral nervous system (P <.001), whereas β2M and FLCs were associated with renal, cutaneous, and biological domains (P <.001 in all cases).
According to multivariate analysis, BAFF and β2M, as well as the interaction between the 2 biomarkers, were found to be independent predictors of total ESSDAI and ClinESSDAI scores. Although FLCs were also determined to be associated with both scores, this association was not independent of immunoglobulin G (IgG) levels. Despite these relationships, multivariate models only displayed modest abilities to explain actual score variations.
Study strengths included the large sample size, which allowed evaluation of biomarker relationships to ESSDAI domains. Study limitations included shortcomings inherent to the ESSDAI, inability to establish FLC predictive value independent of serum IgG, and relatively weak associations that left the clinical significance uncertain.
In discussing the various biomarker and subdomain relationships, the authors noted, “These differing associations are consistent with there being only weak to moderate correlation of FLCs and β2M with BAFF levels, and indicate that these biomarkers provide complementary and non-redundant information.” They recommended that future longitudinal studies be conducted to further establish the role of these 3 biomarkers in pSS and to identify other potential laboratory markers useful for diagnosis and treatment.
Disclosures: AP and SH are employees of The Binding Site. All other authors have declared no conflicts of interest.
James K, Chipeta C, Parker A, et al. B-cell activity markers are associated with different disease activity domains in primary Sjögren’s syndrome. Rheumatology (Oxford). 2018;57(7):1222-1227.