Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome

Abstract

Recent studies suggest that elevated CXCL13 serum levels in patients with primary Sjögren’s syndrome (pSS) associate with minor salivary gland (MSG) histologic features, disease severity, as well as high-risk status for non-Hodgkin lymphoma (NHL) development and NHL itself. In contrast, limited discriminative value of CXCL13 saliva levels has been reported. Prompt by these reports, we sought to validate the clinical utility of CXCL13 by investigating potential correlations of serum and saliva levels with MSG histopathologic [including CXCL13+-cell number, severity of infiltrates and germinal center (GC) formation], serologic and clinical parameters, as well as NHL. CXCL13 levels were evaluated in paired serum and saliva specimens of 45 pSS patients (15 with NHL; pSS-associated NHL: SSL), 11 sicca-controls (sicca-complaining individuals with negative MSG biopsy and negative autoantibody profile), 10 healthy individuals (healthy-controls) and 6 non-SS-NHLs. CXCL13+-cells were measured in paired MSG-tissues of 22 of pSS patients studied (including 7 SSLs) and all sicca-controls. CXCL13 serum levels were significantly increased in pSS and SSL patients compared to sicca- and healthy-controls and were positively correlated with the CXCL13+-cell number and biopsy focus-score. Serum CXCL13 was significantly higher in pSS patients with GCs, rheumatoid factor, hypocomplementemia, high disease activity, NHL and in high-risk patients for NHL development. CXCL13 saliva levels were significantly increased in SSL patients (compared to non-SS-NHLs), patients with GCs and in high-risk for NHL patients. Univariate analysis revealed that CXCL13 serum, but not saliva, levels were associated with lymphoma, an association that did not survive multivariate analysis. Conclusively, our findings confirm that serum, but not saliva, levels of CXCL13 are associated with histologic, serologic and clinical features indicative of more severe pSS.

Sjögren's syndrome: one year in review 2022

“…Among them, CTA-250D10.23 lncRNA was identified as the most significant associated with infiltration events, and a functional annotation analysis revealed a relevance to chemokine signalling pathways (14). Of added interest, a strong correlation between CTA-250D10.23 lncRNA and the serum levels of chemokine CXCL13, which serves as a histologic and clinical biomarker of the disease, was also shown (15,16).…”

“…• Differentially expressed mi-RNAs and lncRNAs have been associated to glandular infiltrate severity, B-cell hyperactivity and chemokine signalling (9)(10)(11)(12)(13)(14)(15)(16). Epigenetics along with other multiomic data allowed to reclassify pSS patient revealing the existence of three pathologic clusters (inflammatory, lymphoid, interferon) and one undefined/normal (17)(18).…”

“…Chatzis et al (15) disease severity and risk of lymphoma development. Focusing on the heterogeneity of salivary gland immunopathology in pSS, the authors remarked the role of FS and ectopic lymphoid structures as more relevant histopathological stratifiers.…”

Update zum Sjögren-Syndrom: Diagnostik & Therapie

“…Immer häufiger wird auch die genauere Unterteilung des unter anti-SSA/Ro-Antiköper subsummierten Ro52 (TRIM21) und Ro60 (TROVE) bedeutsam. Wie von Robbinson et al (2019)und Zampeli et al (2020) gezeigt, scheinen doppelt positive PatientInnen (Ro52 + und Ro60 + ) signifikant häufiger unter Hypergammaglobulinämie, Leukopenie, sowie Speicheldrüsenschwellungen und Lymphomen zu leiden 36 37 . Gleichzeitig scheint diese Subspezifizierung auch die Spezifität der SjS-Antikörperdiagnostik erhöhen zu können, da bei dreifach positiven PatientInnen (Ro52 + , Ro60 + und La + ) SjS die wahrscheinlichste Diagnose darstellte.…”

Integrated Analysis Identifies Upregulated SAMD9L as a Potential Biomarker Correlating with the Severity of Primary Sjögren’s Syndrome

“…A recent example is the CXCL13 gene, which has been shown to be a promising biomarker reflecting the inflammatory infiltrate in SS. 7 In recent years, advancements in genome sequencing technologies have led to the generation of a tremendous volume of high-throughput biomedical data, which require extensive bioinformatics to process and interpret these data. Various tools have been developed for the integrative analysis of transcriptomic profiles in bulk samples, providing opportunities to identify potential prognostic markers and therapeutic targets.…”