Interleukin‐25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

Guggino, Giuliana; Lin, Xiang; Rizzo, Aroldo; Xiao, Fan; Saieva, Laura; Raimondo, Stefania; Liberto, Diana Di; Candore, Giuseppina; Ruscitti, Piero; Cipriani, Paola; Giacomelli, Roberto; Dieli, Francesco; Alessandro, Riccardo; Triolo, Giovanni; Lu, Liwei; Ciccia, Francesco

doi:10.1002/art.40500

Cited by 22 publications

(26 citation statements)

References 30 publications

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“…IL‐25 has been only reported in pSS at the local level: high mRNA expression in LSG biopsy, and it had been related to inducing type 2 innate lymphoid cells. The precise effect at the systemic level is unknown 11 . Nevertheless, IL‐25 levels presented a median value than was not exceed to 1 pg/mL in both groups (pSS: 0.5 pg/mL and CS: 0.009 pg/mL), and these levels should be taken carefully.…”

Section: Discussionmentioning

confidence: 94%

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Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups

López-Villalobos

Muñoz‐Valle

Palafox‐Sánchez

et al. 2020

Clinical Laboratory Analysis

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Background Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups. Methods Ninety‐nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K‐mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal‐Wallis test and the Bonferroni test. Results Higher IFN‐γ, IL‐17F, IL‐21, IL‐23, IL‐4, and IL‐31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity. Conclusion Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.

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Section: Discussionmentioning

confidence: 94%

“…About inductors and maintainers of Th2 response, IL‐33 was identified at glandular and soluble expression without clinical association in pSS 9,10 . Moreover, high IL‐25 mRNA expression from LSG associated with the lymphocytic infiltration was reported 11 …”

Section: Introductionmentioning

confidence: 99%

Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups

López-Villalobos

Muñoz‐Valle

Palafox‐Sánchez

et al. 2020

Clinical Laboratory Analysis

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“…On the other hand, IL-17E/IL-17RB interaction can promote Th2 responses, regulate B cell function, and induce Th17driven autoimmune inflammation (25). In SS patients, it was reported to participate in pathogenesis by promoting inflammation (26). Thus, we speculated that anti-IL-17RB antibodies may act as agonist of IL-17RB and play a potentially similar proinflammatory role in TAK patients.…”

Section: Discussionmentioning

confidence: 96%

Identification of Novel Serological Autoantibodies in Takayasu Arteritis Patients Using HuProt Arrays

Wen

Song

et al. 2021

Molecular & Cellular Proteomics

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To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach. A two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In Phase II, the identified candidate autoantibodies were validated with TAK-focused arrays using an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in Phase II were further confirmed using Western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635 and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB and NOLC1 showed good specificities of 88.3%, 85.9% and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantibodies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared to that by each individual biomarker. The performance of three autoantibodies, namely anti-SPATA7, -QDPR and -PRH2, were successfully confirmed with Western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK–specific biomarker candidates, three of which could be readily adopted in a clinical setting.

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“…Our previous studies have demonstrated that Th17 cells are important in initiating the pathogenesis of SS, indicating a key role for IL-17A in SS (7) provokes inflammation in airways causing persistent asthma symptoms, which can be activated by IL-25. Therefore, available studies have indicated that IL-25 plays a pathogenic role during the development of SS (50,93).…”

Section: Sjö Gren's Syndromementioning

confidence: 99%

Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis

et al. 2021

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Interleukin-17E (IL-25) is a member of the IL-17 cytokine family that includes IL-17A to IL-17F. IL-17 family cytokines play a key role in host defense responses and inflammatory diseases. Compared with other IL-17 cytokine family members, IL-25 has relatively low sequence similarity to IL-17A and exhibits a distinct function from other IL-17 cytokines. IL-25 binds to its receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor B (IL-17RB) for signal transduction. IL-25 has been implicated as a type 2 cytokine and can induce the production of IL-4, IL-5 and IL-13, which in turn inhibits the differentiation of T helper (Th) 17. In addition to its anti-inflammatory properties, IL-25 also exhibits a pro-inflammatory effect in the pathogenesis of Th17-dominated diseases. Here, we review recent advances in the roles of IL-25 in the pathogenesis of inflammation and autoimmune diseases.

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Interleukin‐25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

Abstract: IL-25 may promote the inflammatory state in primary SS and may be a potential target for novel disease-modifying therapeutic strategies in patients with primary SS.

Cited by 22 publications

References 30 publications

Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups

Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups

Identification of Novel Serological Autoantibodies in Takayasu Arteritis Patients Using HuProt Arrays

Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis

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