Serum Levels of Beta2-Microglobulin and Free Light Chains of Immunoglobulins Are Associated with Systemic Disease Activity in Primary Sjögren’s Syndrome. Data at Enrollment in the Prospective ASSESS Cohort

Abstract

ObjectivesTo analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sjögren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment.MethodsThree hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the “Assessment of Systemic Signs and Evolution of Sjögren's Syndrome” (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).ResultsPatient median age was 58 (25th–75th: 51–67) and median disease duration was 5 (2–9) years. Median ESSDAI at enrollment was 2 (0–7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]–[11] vs 2 [0–7], P = 0.03; 4 [1]–[11] vs 2 [0–7], P< 0.0001); 4 [2]–[10] vs 2 [0–6.6], P< 0.0001 and 4 [2–8.2] vs 2 [0–7.0], P = 0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1–3665.5) vs 898.9 (715.9–1187.2) pg/ml, P = 0.01 and 2.6 (2.2–2.9) vs 2.1 (1.8–2.6) mg/l, P = 0.04, respectively).ConclusionIn pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity.

The value of rituximab treatment in primary Sjögren's syndrome

“…Serum immunoglobulin free light chains (FLCs) are also affected by rituximab and decrease significantly from week 5 up to week 48 after treatment (unpublished data), in line with findings in RA [19]. Both β2-microglobulin and FLC baseline levels in serum of pSS patients are positively correlated to ESSDAI scores [20], suggesting that there is a link between the degree of B cell activation and systemic disease activity. Serum levels of several B cell-associated cytokines, including IL-6, GM-CSF, TNF-α and IL-10, are also lowered by rituximab [21].…”

Defining disease activity states and clinically meaningful improvement in primary Sjögren's syndrome with EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI)

“…Between 2009 and 2011, 395 patients with primary SS according to AECG were included from 15 centres of Rheumatology and Internal Medicine in France in the ‘Assessment of Systemic Signs and Evolution of SS’ (ASSESS) 5-year prospective observational cohort that aim to identify predictive factors of systemic complications 6 7. Therapeutic management was left to the discretion of treating physician.…”

Development of the ClinESSDAI: a clinical score without biological domain. A tool for biological studies

“…Compared with previous study that logically used the ESSDAI as reference disease activity measure,6 27–29 the forthcoming studies will avoid the pitfall of circular reasoning induced by collinearity of data, since the clinESSDAI will allow a measure of activity independent of B-cell biomarkers.…”

“…This domain is the more frequently involved ESSDAI domain affecting one-third to two-thirds of the patients in recent cohorts 3 6 7. In the context of biological studies focusing on identification of new biomarkers, association with disease activity is a crucial question to be answered, since the purpose of these markers is to know if they are implicated in the disease process.…”