Expression of interleukin‐17 in primary Sjögren's syndrome and the correlation with disease severity: A systematic review and meta‐analysis

Zhang, L.‐W.; Zhou, Peiru; Pan, Wei; Cong, Xin; Wu, Li‐Ling; Hua, Hong

doi:10.1111/sji.12649

Cited by 34 publications

(24 citation statements)

References 77 publications

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“…However, this SNP is located on the third intron of the STAT4 gene and the precise mechanism that leads to the higher expression of STAT4 remains unclear. As in SS, the IL-17 axis gives a great contribution to the development and maintenance of the local inflammatory process [36]; it is also relevant to remind the known implication of STAT4 in Th17 response [37, 38]. According to this background, the association that we found between a STAT4 SNP and the aberrant production of autoantibodies, cryoglobulins, and monoclonal component could be more easily explained.…”

Section: Discussionmentioning

confidence: 61%

STAT4,TRAF3IP2,IL10, andHCP5Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects

Colafrancesco

Ciccacci

Priori

et al. 2019

Journal of Immunology Research

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Sjögren’s syndrome (SS) is a chronic autoimmune condition characterized by autoantibody production, sicca syndrome, and periepithelial lymphocytic lesions in target tissues. A predisposing genetic background is likely, and, to date, several polymorphisms in non-HLA genes have been explored with interesting results. We investigated the association between the STAT4, TRAF3IP2, HCP5, and IL10 polymorphisms and SS susceptibility and their possible role in the modulation of clinical and laboratory features. 195 consecutive patients with SS were enrolled and clinical and laboratory data were collected. 248 age- and sex-matched healthy subjects were used as controls. Genotyping was performed by allelic discrimination assays. A case-control association study and a phenotype-genotype correlation analysis were performed. A genetic risk profile was developed considering the risk alleles. Both the variant alleles of rs7574865 in the STAT4 gene and rs3099844 in the HCP5 gene were significantly more prevalent in patients than in controls (OR=1.91 and OR=2.44, respectively). The variant allele of rs3024505 of IL10 resulted to be a susceptibility allele (OR=1.52), while the variant allele of rs1800872 seemed to confer a protective effect for the development of the disease (OR=0.65). A risk genetic profile showed a higher probability to develop the disease in subjects with at least three risk alleles; subjects with 4 risk alleles were not observed in the controls. HCP5 rs3099844 was associated with anti-SSA (P=0.006, OR=3.07) and anti-SSB (P=0.005, OR=2.66) antibodies, severity of focus score (P=0.03, OR=12), and lymphoma development (P=0.002, OR=7.23). Patients carrying the STAT4 rs7574965 variant allele had a higher risk of monoclonal component and leukopenia (P=0.002, OR=7.6; P=0.048, OR=2.01, respectively). We confirmed the association of SS with the STAT4 and IL10 genes and we describe a novel association with HCP5. In particular, we describe an association of this specific SNP of HCP5 not only with disease development but also with autoantibody production and focus score suggesting a potential contribution of this variant to a more severe phenotype.

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Section: Discussionmentioning

confidence: 61%

STAT4,TRAF3IP2,IL10, andHCP5Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects

Colafrancesco

Ciccacci

Priori

et al. 2019

Journal of Immunology Research

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“…Currently, new evidence indicates that IL‐17 and IL‐22 are implicated in the pathogenesis of EMT‐dependent fibrosis, reporting that IL‐17 triggers the EMT in airway epithelial cells dependent on transforming growth factor (TGF)‐β1 , and IL‐22 determines a dramatic up‐regulation of TGF‐β, α‐SMA gene expression, laminin, hyaluronic acid and collagen type IV in human hepatic stellate cells, promoting pathological liver fibrosis . Interestingly, elevated IL‐17 and IL‐22 levels are detected in SG tissue and serum of patients with pSS, clearly correlated with serological markers of pSS disease or the focus score (FS) , suggesting their key participation in this disease pathogenesis . As the EMT is induced by a dramatic up‐regulation of cytokines and has an important role in promoting the progression of fibrosis, it would be interesting to determine whether IL‐17‐/IL‐22‐dependent EMT occurs in pSS SG tissue and to correlate the EMT with the severity of the pSS inflammatory grade.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17 and -22 synergy linking inflammation and EMT-dependent fibrosis in Sjögren’s syndrome

Sisto

Lorusso

Tamma

et al. 2019

Clinical and Experimental Immunology

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Summary Primary Sjögren’s syndrome (pSS) is a chronic inflammatory, autoimmune and systemic disorder commonly associated with dry eyes and a dry mouth. Recently, the hypothetical link between epithelial–mesenchymal transition (EMT)‐dependent salivary gland (SG) fibrosis and chronic inflammatory conditions has been suggested. In this study, we present data demonstrating a negative correlation of the epithelial marker E‐cadherin expression and a positive correlation of mesenchymal vimentin and collagen type I expression with increasing degrees of tissue inflammation in pSS SG specimens. In addition, as it is not clear whether dysregulated cytokines in pSS, interleukin (IL)‐17 and IL‐22 may also contribute to the EMT‐dependent fibrosis process, the effect of IL‐17 and IL‐22 treatment on EMT‐dependent SG fibrosis was evaluated in primary human salivary gland epithelial cells (SGEC) isolated from healthy subjects. Here we present data demonstrating that IL‐17 and IL‐22 can induce SGEC to undergo a morphological and phenotypical transition to a mesenchymal phenotype. In support of this, vimentin and collagen type I were up‐regulated while a decreased expression of E‐cadherin occurs after interleukin treatment, and co‐operation between IL‐17 and Il‐22 was required to induce the EMT.

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“…This possibility relies on the central role of IL-17 expression in cooperating to the production and to the activation of IL-22 and its related pathway, which has been demonstrated to strongly endorse inflammation in pSS. Trials attempting to assess efficacy of Secukinumab and Ixekizumab, mAb targeting Il-17, in pSS are awaited [151,152].…”

Section: Discussionmentioning

confidence: 99%

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

et al. 2020

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Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players. A better knowledge of such processes could determine the detection of new therapeutic targets that are a major need for pSS.

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Expression of interleukin‐17 in primary Sjögren's syndrome and the correlation with disease severity: A systematic review and meta‐analysis

Cited by 34 publications

References 77 publications

STAT4,TRAF3IP2,IL10, andHCP5Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects

STAT4,TRAF3IP2,IL10, andHCP5Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects

Interleukin-17 and -22 synergy linking inflammation and EMT-dependent fibrosis in Sjögren’s syndrome

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

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