J Transl Med
Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49, North Garden Road, Beijing, 100191, China.
Published: January 2025
Background: Sjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS).
Methods: Our study leveraged the genetic variants of multi-omics statistics extracted from genome-wide association study (GWAS), the University of Bristol and the FinnGen study. We performed a bidirectional Mendelian randomization and mediation study based on randomly allocated instrumental variables to infer causality, followed by external validation with UK Biobank data and Bayesian colocalization.
Results: We demonstrated that an elevated level of CD27 on IgD + CD24 + B cell, a subset of B cells expressing both IgD and CD24, was associated with a higher risk of SS (OR = 1.119, 95% CI: 1.061-1.179, P < 0.001), while CD3 on CD45RA + CD4 + Treg was a protective factor (OR = 0.917, 95%CI: 0.877-0.959, P < 0.001). Results of meta-analysis and colocalization further supported the significant results identified in the primary analysis. A total of 4 inflammatory cytokines and 7 circulating proteins exhibited potential causal relationships with SS despite no significant result achieved after FDR correction. Finally, results of mediation analysis indicated that CD40L receptor levels had significant mediating effects (β = 0.0314, 95% CI: 0.0004-0.0624, P = 0.0471) at a mediation proportion of 28% (95% CI: 0.364%-55.6%) in causal relationship between CD27 on IgD + CD24 + B cell and SS.
Conclusions: By providing a novel genetic insight into unveiling the roles of autoimmunity and inflammation in Sjogren syndrome, our findings may potentially lead to identifying new clinical biomarkers for disease monitoring and therapeutic targets that offer more effective alternatives for treating this condition. Therefore, our study may provide valuable evidence for future clinical intervention and targeted immunotherapy.
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Cureus
December 2024
Nephrology Department, Unidade Local de Saúde (ULS) Algarve - Hospital de Faro, Faro, PRT.
Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by the deposition of fibrils within the mesangium and glomerular basement membrane. Most cases are idiopathic, but it can be linked to autoimmune diseases, neoplasms, and infections. There is limited evidence on the best treatment approach, and many patients progress to end-stage kidney disease.
View Article and Find Full Text PDFCornea
January 2025
Department of Ophthalmology, University of Cyprus Medical School, Nicosia, Cyprus.
Purpose: To assess the impact of autologous serum (AS) tears at a 50% concentration on the ocular surface of patients with refractory dry eye disease (DED) because of Sjogren syndrome.
Methods: Twenty eyes of ten patients with severe immune-mediated DED were contralaterally randomized to receive either AS tears 50% or artificial tears between June 2021 and May 2023. Changes in tear stability, ocular surface staining, and in the morphology of the corneal sub-basal nerves were evaluated before treatment and at 1, 2, and 3 months after treatment using objective tests for DED and confocal microscopy.
Invest Ophthalmol Vis Sci
January 2025
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Purpose: To investigate the role of S100A8/A9 in the pathogenesis of Sjögren's dry eye disease (SjDED) and explore its potential mechanism of action.
Methods: S100A8/A9 expression was determined by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Tear secretion, corneal fluorescein staining, and hematoxylin and eosin staining were used to evaluate the effect of paquinimod, a S100A8/A9 inhibitor, on dry eye disease in nonobese diabetic (NOD) mice.
J Transl Med
January 2025
Department of Rheumatology and Immunology, Peking University Third Hospital, No. 49, North Garden Road, Beijing, 100191, China.
Background: Sjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS).
View Article and Find Full Text PDFPLoS One
January 2025
Department of Neuroscience, Laboratory of Prion Neurobiology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
There is no cure for Marinesco-Sjögren syndrome (MSS), a genetic multisystem disease linked to loss-of-function mutations in the SIL1 gene, encoding a BiP co-chaperone. Previously, we showed that the PERK kinase inhibitor GSK2606414 delays cerebellar Purkinje cell (PC) degeneration and the onset of ataxia in the woozy mouse model of MSS. However, GSK2606414 is toxic to the pancreas and does not completely rescue the woozy phenotype.
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