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

James, Katherine; Chipeta, C.; Parker, Antony R.; Harding, Stephen; Cockell, Simon; Gillespie, Colin S.; Hallinan, Jennifer; Barone, Francesca; Bowman, Simon; Ng, Wan Fai; Fisher, Benjamin A; Registry, . Uk Primary Sjögren's Syndrome

doi:10.1093/rheumatology/key063

Cited by 27 publications

(27 citation statements)

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“…As α 1 -MG is not an acute phase protein, variations in its urinary levels can be safely inferred not to be caused by a transient state of systemic inflammation (30). While FLC and β2M testing may also be associated with renal damage, their role as diagnostic biomarkers was not considered yet (26).…”

Section: Discussionmentioning

confidence: 99%

“…Area under the curve was best for the combination of creatinine and α 1 -MG, with a significant difference compared to creatinine alone (0.824 vs. 0.777) (24). In 2018, a study was published in which B-cell activity markers and organ involvement in pSS were considered (26). Levels of serum free light chains (FLC) and β2-microglobulin (β2M) were found to be associated with renal disease.…”

Section: Predisposing Factors and Emerging Biomarkersmentioning

confidence: 99%

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Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome

et al. 2020

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Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and may affect several organs. Renal involvement has long been known as one of the systemic complications of pSS. The most classical lesion observed in pSS is tubulointerstitial nephritis (TIN) and less frequently membranoproliferative glomerulonephritis (MPGN), which is related to cryoglobulinemia. In some cases, renal biopsy is necessary for the definitive diagnosis of kidney involvement. Patients may present with proximal renal tubular acidosis, distal renal tubular acidosis and chronic kidney disease. Response to treatment is usually favorable. However, occasionally severe and rarely lethal outcomes have been described. Recently, several case series and cross-sectional studies have been published which investigated the factors associated with renal involvement in pSS and the most accurate screening tests for early detection. The presence of xerophthalmia, anti-SSA and rheumatoid factor positivity, low C3 levels and other features have all shown either positive or inverse associations with the development of renal complications. Serum creatinine, alpha-1-microglobulin, cystatin-C have been evaluated as early detection biomarkers with variable accuracy. More advanced techniques may be necessary to confirm proximal and distal renal tubular acidosis, along with nephrogenic diabetes insipidus. The aim of the current paper is to summarize and critically examine these findings in order to provide updated guidance on serum biomarkers and further testing for kidney involvement in pSS.

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Section: Discussionmentioning

confidence: 99%

Section: Predisposing Factors and Emerging Biomarkersmentioning

confidence: 99%

Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome

et al. 2020

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“…Anti-Ro/SSA, anti-La/SSB, RF, IgG, immunoglobulin A (IgA), immunoglobulin M (IgM), C3, C4, ESR, white blood cell count (WCC) and C-reactive protein (CRP) were measured by the clinical laboratory of the recruiting hospitals. BAFF, β2 microglobulin (B2M), κ light chain, λ light chain, κ-λ ratio, and combined free light chains (CMBY) were measured by The Binding Site (Birmingham, UK) as previously described [24].…”

Section: Measurement Of Serum B-cell and Inflammatory Markersmentioning

confidence: 99%

Serum CXCL13 levels are associated with lymphoma risk and lymphoma occurrence in primary Sjögren’s syndrome

Traianos

Locke²,

Lendrem

et al. 2020

Rheumatol Int

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Primary Sjögren's syndrome (pSS) is an autoimmune disease characterised by an increased risk for non-Hodgkin lymphoma (NHL) development. Ectopic germinal centre (GC) in the salivary gland is associated with increased NHL risk in pSS, and the chemokine CXCL13 is implicated in B-cell migration and GC formation. Serum CXCL13 concentrations were quantified by ELISA in 48 healthy individuals, 273 pSS patients without NHL (pSS-nonL), and 38 pSS patients with NHL (pSS-NHL+) from the United Kingdom Primary Sjögren's Syndrome Registry cohort. PSS-nonL patients were stratified into low risk (LR), moderate risk (MR) and high risk (HR) groups according to the lymphoma risk score proposed by Fragkioudaki et al. Differences in serum CXCL13 levels among groups were analysed using the Wilcoxon method. Also, changes in serum CXCL13 over a time period of at least 1 year and a median 4 years were assessed for 200 pSS-nonL and 8 pSS-NHL+ patients. In addition, associations of serum CXCL13 with B-cell and inflammatory markers were investigated by correlation analyses and logistic regression. Serum CXCL13 levels were higher in all pSS groups compared to controls (p < 0.0001), and in pSS-NHL+ compared to pSS-nonL patients (p = 0.0204). LR patients had lower CXCL13 levels than MR patients (p < 0.0001) and pSS-NHL+ patients (p = 0.0008). CXCL13 levels remained stable over the study period for all pSS groups. CXCL13 was associated (p < 0.0005) with Immunoglobulin G (IgG), B-cell activating factor, β2 microglobulin, combined free light chains, κ and λ light chains, anti-Ro/SSA, anti-La/SSB, and erythrocyte sedimentation rate. IgG and C3 controlled for age and gender were significantly associated with NHL risk in pSS. Serum CXCL13 levels were elevated in pSS-NHL+ and MR patients compared to LR patients and remained stable over time. Further study is required to investigate the role of CXCL13 in pSS-associated NHL risk.

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“…However, we are unaware of studies that focus on the effects of dysregulation of transcriptomes, including lncRNAs, of B cells on the pathogenesis of pSS. Serum level of B cell-activating factor was associated with disease activity of pSS [16][17][18]. In addition, the distribution of peripheral B cell subsets is profoundly altered in patients with pSS [19].…”

Section: Introductionmentioning

confidence: 97%

Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren’s syndrome

et al. 2020

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Background: The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren's syndrome (pSS) at the transcriptome level. Methods: We enrolled patients with pSS (n = 6) and healthy controls (HCs) (n = 6) in the discovery cohort using microarray and pSS (n = 14) and HCs (n = 12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38 − IgD + (Bm1), CD38 + IgD + (naive B cells), CD38 high IgD + (pre-germinal centre B cells) and CD38 ± IgD − (memory B cells). We performed differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA). Results: Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene. Conclusion: Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS. Trial registration: Not required.

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

Cited by 27 publications

References 21 publications

Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome

Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome

Serum CXCL13 levels are associated with lymphoma risk and lymphoma occurrence in primary Sjögren’s syndrome

Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren’s syndrome

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