B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome.

Katherine James,Wan-Fai Ng,Colin S Gillespie,Chimwemwe Chipeta,Jennifer Hallinan,Simon J Bowman,Antony Parker,Benjamin A Fisher,Stephen Harding,Francesca Barone,Simon J Cockell

doi:10.1093/rheumatology/key063

Abstract

ObjectivesB-cell activating factor (BAFF), β-2 microglobulin (β2M) and serum free light chains (FLCs) are elevated in primary SS (pSS) and associated with disease activity. We aimed to investigate their association with the individual disease activity domains of the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) in a large well-characterized pSS cohort.MethodsSera from pSS patients enrolled in the UK Primary Sjögren’s Syndrome Registry (UKPSSR) (n = 553) and healthy controls (n = 286) were analysed for FLC (κ and λ), BAFF and β2 M. Pearson correlation coefficients were calculated for patient clinical characteristics, including salivary flow, Schirmer’s test, EULAR Sjögren’s Syndrome Patient Reported Index and serum IgG levels. Poisson regression was performed to identify independent predictors of total ESSDAI and ClinESSDAI (validated ESSDAI minus the biological domain) scores and their domains.ResultsLevels of BAFF, β2M and FLCs were higher in pSS patients compared to controls. All three biomarkers associated significantly with the ESSDAI and the ClinESSDAI. BAFF associated with the peripheral nervous system domain of the ESSDAI, whereas β2M and FLCs associated with the cutaneous, biological and renal domains. Multivariate analysis showed BAFF, β2M and their interaction to be independent predictors of ESSDAI/ClinESSDAI. FLCs were also shown to associate with the ESSDAI/ClinESSDAI but not independent of serum IgG.ConclusionAll biomarkers were associated with total ESSDAI scores but with differing domain associations. These findings should encourage further investigation of these biomarkers in longitudinal studies and against other disease activity measures.

Highlights

Primary SS is characterized by autoimmune inflammation of exocrine glands resulting in severe dryness
Levels of BAFF, b-2 micgroglobulin (b2M) and free light chains (FLCs) were higher in Primary SS (pSS) patients compared to controls
BAFF associated with the peripheral nervous system domain of the EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI), whereas b2M and FLCs associated with the cutaneous, biological and renal domains

Summary

Introduction

Primary SS (pSS) is characterized by autoimmune inflammation of exocrine glands resulting in severe dryness. B-cell hyperactivity has been implicated in the pathogenesis and may contribute to the development of systemic manifestations [1, 2]. The EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI), was introduced with the aim of providing clinicians with a way of objectively measuring disease activity in pSS [3]. The ESSDAI is comprised of 12 disease activity domains, and is the most commonly used primary outcome measure in pSS clinical trials. In order to avoid confounding in biomarker studies the ClinESSDAI was developed, in which the biological domain has been removed [4]. There is interest in developing biomarkers of disease activity such as histopathology [6, 7], US [8, 9] and serum measures of B-cell activity. BAFF promotes the survival and proliferation of B cells and mice overexpressing BAFF develop Sjogren’s-like features [2]

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