TNFA -308G&gt;A and -238G&gt;A polymorphisms and risk to systemic sclerosis: impact on TNF-α serum levels, TNFA mRNA expression, and autoantibodies

Lomelí-Nieto, José Alvaro; Muñoz‐Valle, José Francisco; Baños‐Hernández, Christian Johana; Navarro‐Zarza, José Eduardo; Ramírez‐Dueñas, Maria Guadalupe; Sánchez‐Hernández, Pedro Ernesto; Machado-Sulbaran, Andrea Carolina; Parra‐Rojas, Isela; García‐Chagollán, Mariel; Hernández‐Bello, Jorge

doi:10.1007/s10238-019-00569-4

Cited by 10 publications

(18 citation statements)

References 41 publications

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“…Extensive research has identified a strong primary association of TNF-863A and TNF-1031C alleles with ACA-positivity as well as TNF-857T allele with ATAs in SSc ( 64 ). Recent evidence indicated that TNFA polymorphisms, associated with higher sTNF-α levels, positively correlate with ARAs levels ( 65 ).…”

Section: Classical Disease-specific Autoantibodies In Clinical Manifementioning

confidence: 99%

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

et al. 2020

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Systemic sclerosis (SSc) is an autoimmune disease characterized by abnormalities in microcirculation, extracellular matrix accumulation, and immune activation. Autoantibodies are markers of immune abnormalities and provide diagnostic and predictive value in SSc. Anti-topoisomerase antibodies (ATAs), anticentromere antibodies (ACAs), and anti-RNA polymerase antibodies (ARAs) are the three classical specific antibodies with the highest availability and stability. In this review, we provide an overview of the recent progress in SSc research with respect to ATAs, ACAs, and ARAs, focusing on their application in distinguishing clinical phenotypes, such as malignancy and organ involvement, identifying genetic background in human leukocyte antigen (HLA) or non-HLA alleles, and their potential roles in disease pathogenesis based on the effects of antigen-antibody binding. We finally summarized the novel analysis using ATAs, ACAs, and ARAs on more detailed disease clusters. Considering these advantages, this review emphasizes that classical SSc-specific autoantibodies are still practical and have the potential for patient and risk stratification with applications in precise medicine for SSc.

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Section: Classical Disease-specific Autoantibodies In Clinical Manifementioning

confidence: 99%

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

et al. 2020

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“…Immunological dysregulation which includes autoimmunity, in ltration and activation of immune cells is the essential feature of SSc [17,18]. B cells have been involved in the pathogenesis of SSc directly as well as indirectly through producing autoantibodies and releasing proin ammatory/pro brotic cytokines and chemokines [17,35,36]. Previous studies reported that SSc patients showed altered B-cell homeostasis and activation with increased B-cells but decreased memory B-cells [19,22,23].…”

Section: Discussionmentioning

confidence: 99%

Baicalein Alleviates Fibrosis and Inflammation in Scleroderma Through Regulating B Cell Abnormalities

Peng

et al. 2021

Preprint

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Background Scleroderma (Systemic sclerosis, SSc) is an autoimmune disorder characterized by multisystem extensive fibrosis, vascular changes and immunological dysregulation. B cell abnormalities play an essential role in the fibrotic pathogenesis of scleroderma by promoting autoantibodies and cytokines release as well as modulating the inflammatory processes. Baicalein, a phenolic flavonoid derived from the Chinese herb Scutellaria baicalensis Georgi, has been used in the treatment of the pathological processes of various fibrotic and inflammatory diseases. Here, we aimed to investigate the effect of baicalein on the major pathological characteristics of SSc both in vitro and in vivo, including fibrosis, B cell abnormalities and inflammation. Methods The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. The antifibrotic features of baicalein and its mechanisms were investigated in the bleomycin (BLM)-induced dermal fibrosis mice model by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay and flow cytometry. Results 5-120 µM baicalein significantly abrogated total collagen deposition, decreased soluble collagen secretion, and inhibited the expression of various fibrogenesis molecules, including collagen(COL)1A1, COL1A2, COL3A1, connective tissue growth factor (CTGF), fibronectin, transforming growth factor β1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) in both TGF β1- and PDGF-induced human CCC-ESF-1 dermal fibroblasts. In BLM-induced dermal fibrosis mice model, 25-100 mg/kg baicalein markedly attenuated dermal thickness and collagen accumulation in dose-dependent manners. Baicalein reduced the proportion of B220+ B cells, while increased the percentage of CD27+ memory B cells in the spleen of BLM-induced mice. Consistent with reversing B cell abnormalities, baicalein treatment potently attenuated serum levels of cytokines(IL-1β, IL-2, IL-4, IL6, IL-17A, TNF-α), chemokines (MCP-1, MIP-1β) and autoantibodies (anti-Scl-70, anti-PM-Scl, anti-centromeres and anti-dsDNA). Conclusions Baicalein inhibits TGF-β1 and PDGF- mediated ECM accumulation in human dermal fibroblasts and alleviates the development of experimental dermal fibrosis by reversing B cell abnormalities, reducing autoantibody production and ameliorating inflammation. Baicalein may have the potential to be further developed as a therapeutic candidate against SSc.

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“…( http://wwwn.cdc.gov/epiinfo/html/downloads.htm ) to detect a difference between case and control groups, assuming an odds ratio (OR) of 2.0 with a power of 0.8 and 5 % type I error. The OR was based on previous evidence [ 22 – 24 ], and at least 128 athletes per group was necessary.…”

Section: Methodsmentioning

confidence: 99%

Association of TNF-α -308G > A polymorphism with susceptibility to tendinopathy in athletes: a case–control study

Lopes

Miranda

Guimarães

et al. 2021

BMC Sports Sci Med Rehabil

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Background High levels of the tumor necrosis factor alpha (TNF-α) induce apoptosis and pro-inflammatory effects for primary degeneration of tendon and development of tendinopathy. The aim of this study was to investigate the association between the TNF-α polymorphisms and tendinopathy in athletes. Methods Two hundred and seventy athletes (135 tendinopathy cases and 135 controls) were included and genotyped (TNF-α -1031T > C; -857 C > T; -308G > A) using TaqMan validated assays. The association of the polymorphisms with tendinopathy was evaluated by a multivariate logistic regression model, using odds ratios (OR) and 95 % confidence intervals (CI). Results The variant allele − 308 A was significantly associated with patellar (OR: 1.9; 95 % CI: 1.01–3.6) or Achilles tendinopathies (OR: 2.7; 95 % CI: 1.1–6.7). No significant differences were found in allele or genotype distributions of the − 1031T > C and − 857 C > T polymorphisms between cases and controls. TNF-α TCA haplotype was associated with increased tendinopathies risk, either considering all cases (OR: 2.6, 95 % CI: 1.3–5.3), patellar (OR: 3.3, 95 % CI: 1.5–7.3), rotator cuff (OR: 3.1, 95 % CI: 1.4–7.2) or Achilles tendinopathies (OR: 3.8, 95 % CI: 1.1–12.7). Conclusions These results suggest that the TNF-α polymorphisms could influence the susceptibility to developing tendinopathy among athletes. Knowledge of the TNF-α polymorphisms associated to tendinopathy in athletes can further understanding of the inflammatory role in the early stages of the disease and contribute for sports injury surveillance programmes, in which athletes with TNF-α TCA haplotype could be early subjected to cryotherapy after training and competition to avoid tendinopathy development.

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TNFA -308G>A and -238G>A polymorphisms and risk to systemic sclerosis: impact on TNF-α serum levels, TNFA mRNA expression, and autoantibodies

Cited by 10 publications

References 41 publications

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

Baicalein Alleviates Fibrosis and Inflammation in Scleroderma Through Regulating B Cell Abnormalities

Association of TNF-α -308G > A polymorphism with susceptibility to tendinopathy in athletes: a case–control study

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