Serological lymphocytic activity and patient-reported outcomes in Sjögren’s syndrome

Abstract

This study was set to investigate whether serum markers of lymphocytic activity are associated with patient-reported outcomes in Sjögren's syndrome (SS). Forty-six patients with SS were included in this cross-sectional study. Patients with monoclonal gammopathy, history of malignant lymphoma, or with secondary SS were excluded. Serum levels of IgG, β2-microglobulin (β2M), soluble interleukin-2 receptor (sIL2-R), and free light chains (FLC) were assessed. Systemic disease activity was measured by the EULAR SS disease activity index (ESSDAI). Patient-reported symptoms were recorded by visual analogue scales (VAS) of pain, fatigue, and dryness, as compiled in the EULAR SS patient-reported index (ESSPRI). Depressive symptoms were determined by the Patient Health Questionnaire 9 (PHQ-9). Serum concentrations of κFLC (r = 0.491, p = 0.001), λFLC (r = 0.326, p = 0.027), and β2M (r = 0.421, p = 0.004) correlated with the ESSDAI, whereas sIL-2R and IgG did not. No correlations between serum markers of lymphocytic activity and the ESSPRI, or single VAS measures of pain, dryness, or fatigue, were found. In patients with VAS fatigue scores in the upper quartile, sIL-2R serum levels were even decreased (p = 0.019). Only depressive symptoms as determined by PHQ-9 were positively correlated with fatigue (r = 0.536, p < 0.001). In this well-defined cohort of patients with SS, serological lymphocytic activity was not correlated with patient-reported outcomes and sIL-2R levels were even decreased in patients with high fatigue scores. Only depressive symptoms were correlated with fatigue. This highlights the need to further understand the link between inflammation and disease characteristics in SS.

Hypergammaglobulinaemia predicts glandular and extra-glandular damage in primary Sjögren's syndrome: results from the KISS cohort study

“…However, age did not affect ΔIgG in the current study. In line with the existing literature, we found no association between Ig levels and patient-reported outcomes such as PGA, OSDI, XI and ESSPRI (7). The level of IgG decreased most during the first 2 years of observation in patients with hypergammaglobulinaemia at baseline, whereas levels remained steady in those with normal IgG at baseline.…”

“…The biological domain of the European League Against Rheumatism (EULAR) SS Disease Activity Index (ESSDAI), which determines the disease activity of pSS, includes hypergammaglobulinaemia, hypocomplementaemia and cryoglobulinaemia (6). These are prognostic factors for systemic involvement in pSS, which includes skin vasculitis and renal, pulmonary, neurological and haematological involvement (7). In addition, high baseline IgG and low C4 levels predict progression to SS among individuals who do not meet the pSS classification criteria (8).…”

Sjögren’s and non-Sjögren’s sicca share a similar symptom burden but with a distinct symptom-associated proteomic signature

“…7 This would be compatible with observations in persistent interferoninduced fatigue and chronic fatigue syndrome. [8][9][10] In addition, chronic fatigue syndrome has been associated with a metabolic signature. 11 12 Notably, dryness, pain and fatigue are also common symptoms in non-SjS sicca syndrome (sicca), which occurs in the absence of radiotherapy and drug-induced causes and is often assumed to be non-autoimmune with heterogeneous aetiology.…”

Saliva Free Light Chains in Patients with Neuro-Sjögren

“…As B-cell hyperactivity is associated with the pathogenesis of SS and may contribute to the development of systemic manifestations, several B-cell associated biomarkers have been investigated in different body fluids, as follows: B-cell activating factor (BAFF), β2-microglobulin (β2M), soluble interleukin-2 receptor (sIL-2R), and free light chains (FLC) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. FLC are a by-product of the immunoglobulin (Ig) synthesis of B-cells and occur in a predominantly monomeric isoform (kappa free light chains (KFLC)) and a dimeric isoform (lambda free light chains (LFLC)) [ 13 ]. KFLC have already been shown to be a potential diagnostic biomarker for autoimmune-mediated diseases, particularly multiple sclerosis [ 19 , 20 , 21 ].…”

“…Increased serum KFLC and LFLC concentrations have been reported in patients with SS compared with healthy controls [ 14 , 16 , 17 , 22 ]. In addition, FLC concentrations have been found to be associated with disease activity according to the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) and the EULAR Sjögren’s Syndrome Patient-Reported Index (ESSPRI), and FLC concentrations have been proposed as biomarkers for monitoring disease activity and response to treatment [ 12 , 13 , 14 , 15 , 17 , 23 , 24 ]. As lymphocytic infiltration into exocrine glands mediates autoimmune gland inflammation, FLC concentrations in the saliva have been investigated [ 2 , 16 , 17 ].…”