Single‐nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine

Mahmoudi, Hamidreza; Ebrahimi, Elaheh; Daneshpazhooh, Maryam; Balighi, Kamran; Mirzazadeh, Azin; Behjati, Somayeh Elikaei; Tavakolpour, Soheil

doi:10.1111/iji.12451

Cited by 12 publications

(8 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6,7 Association of some gene polymorphisms of immune-mediated genes and cytokines with pemphigus had been shown in several studies. 8 Also, several studies have demonstrated the differences between sera cytokines levels of pemphigus patients and healthy controls (systematically reviewed by Tavakolpour et al 9 ), while there are limited reports regarding different genes' expression profile in comparison with healthy controls. The expression of NLRP1, 10 IPAF, 10 CD19 genes, 11 and some miRNAs including miR-424-5p 12 and miRNA-338-3p 13 were demonstrated to be significantly increased in blood samples of PV and/or PF patients.…”

Section: Introductionmentioning

confidence: 99%

“…Differentiation, activation, proliferation, and function of immune cells are controlled by the immune mediators, such as cytokines and immune checkpoints 6,7 . Association of some gene polymorphisms of immune‐mediated genes and cytokines with pemphigus had been shown in several studies 8 . Also, several studies have demonstrated the differences between sera cytokines levels of pemphigus patients and healthy controls (systematically reviewed by Tavakolpour et al 9 ), while there are limited reports regarding different genes' expression profile in comparison with healthy controls.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

Tavakolpour

Mahmoudi

Karami

et al. 2020

Dermatologic Therapy

Self Cite

View full text Add to dashboard Cite

Pemphigus is a rare group of autoimmune diseases, which its exact molecular pathogenesis and therapeutic biomarkers remained unknown. In this regard the expressions of eight immune-related genes was evalualted in pemphigus patients. Forty-six pemphigus patients, either new case or on minimal therapy, were recruited. The expressions of IL22, IL9, IL21, EBI3, TNFSF13B, FCGR3A, CTLA4, and PDCD1 genes were analyzed at baseline, compared with 32 healthy controls, and their changes were monitored 3 months after rituximab (RTX) therapy through Reverse Transcriptase Real-time PCR (RT-Real-time PCR). Except of IL21, which was similar in both groups, expressions of other genes were significantly lower in patients compared with the controls (P-value <.05). PDCD1, EBI3, IL21, and IL22 genes were significantly overexpressed three months following RTX administration (P-value <.05). Higher prednisolone dosage and PDAI-score were positively correlated with CTLA4 and FCGR3A expressions after 3 months, respectively (P-value = .019 and .048, respectively). Anti-desmoglein 1 (Dsg 1) titer and its positivity at baseline were associated with TNFSF13B expression, FCGR3A expressions, and the PDAI-score. Our results suggest the possible involvement of some gene expressions in pemphigus immunopathogenesis, which could be affected by RTX therapy and also might be used as prognostic biomarkers.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

Tavakolpour

Mahmoudi

Karami

et al. 2020

Dermatologic Therapy

Self Cite

View full text Add to dashboard Cite

show abstract

“…18 The CTLA4 rs231775 variant has been reported to be associated with various autoimmune diseases such as Graves' disease in adults 24 and autoimmune hypothyroidism in children of the Han Chinese population, 25 multiple sclerosis, 26 vitiligo, 7 vasculitis, 27 systemic lupus erythematosus, [28][29][30] rheumatoid arthritis, 31,32 latent autoimmune diabetes in adults, 33 primary biliary cirrhosis, 34 primary biliary cholangitis, 35 and Pemphigus Vulgaris. 36,37 Additionally, a more recent meta-analysis by Wang and colleagues indicated a significant association of CTLA4 rs231775 with autoimmune diseases' susceptibility under different genetic models, highlighting its potential implication as a diagnostic genetic biomarker in both Asian and Caucasian populations. 38 However, our results are not consistent with Song et al and Liang et al meta-analyses 8,9 and partially agree with Birlea et al 4 The latter study showed no association of the specified variant with vitiligo in the overall analysis; however still, a significant one was evident in vitiligo patients with other concomitant autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

Gouda

Fawzy

Toraih

2021

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background Cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population. Methods The CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated. Results A higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk of vitiligo under recessive (OR = 2.94, 95% CI = 1.61–5.35, p < 0.001), dominant (OR = 1.87, 95% CI = 1.14–3.06, p = 0.013), and homozygote comparison (OR = 3.34, 95% CI = 1.73–6.42, p = 0.001) models. Although the CTLA4 relative expression levels were comparable to that of controls, G/G carriers exhibited a significantly lower expression profile (median = 0.63, IQR = 0.34–1.75) than A/A (median = 1.43, IQR = 0.39–4.25, p = 0.018) and A/G carriers (median = 1.68, IQR = 0.49–3.92, p = 0.007). No significant associations of CTLA4 variant/expression with disease severity and/or activity were observed. Conclusion The CTLA4 rs231775 variant was associated with vitiligo susceptibility and gene expression; the risky genotype (GG) was associated with lower CTLA4 relative expression levels than the other genotypes. Further large‐scale studies in different populations are warranted.

show abstract

“…The coexistence of alleles of DRB1*14/DQB1*05 and A*11/DQB1*05 would be strongly influential for the predisposition to the disease, while that of HLA-B*50/DQB1*02 could play a protective role [14]. In addition, multiple single nucleotide polymorphisms within different genes may confer susceptibility to the diseases, probably in a population-specific way [15]. Serological typing for HLA class II antigens in patients with ABD of the pemphigoid type revealed a highly significant association with HLA-DQβ1*0301 [16].…”

Section: Geneticsmentioning

confidence: 99%

Pemphigus Vulgaris and Bullous Pemphigoid: Update on Diagnosis and Treatment

Lernia

Casanova

Goldust

et al. 2020

Dermatol Pract Concept

View full text Add to dashboard Cite

Autoimmune bullous disorders are a heterogeneous spectrum of skin disorders characterized by the production of autoantibodies against adhesion molecules of the skin. The 2 major groups of diseases are “pemphigus diseases” and “autoimmune bullous diseases of the pemphigoid type.” Pemphigus diseases are a group of autoimmune blistering diseases of the skin and mucous membranes characterized by intraepithelial cleft and acantholysis. The main subtypes of pemphigus include pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. Diagnosis is based on clinical manifestations and confirmed with histological, immunofluorescence, and serological testing. Recently multivariant enzyme‐linked immunosorbent assay systems have been developed as practical screening tools for patients with suspected autoimmune bullous dermatoses. The current first-line treatment of pemphigus is based on systemic corticosteroids that are often combined with immunosuppressive adjuvants, such as azathioprine, mycophenolate mofetil, and the anti-CD20 monoclonal antibody rituximab, usually at initiation of treatment. Rituximab efficacy is higher when it is administered early in the course of the disease. Therefore, it should be used as first-line treatment to improve efficacy and reduce cumulative doses of corticosteroids and their side effects. Treatment of bullous pemphigoid is based on disease extension. Localized and mild forms can be treated with superpotent topical corticosteroids or with nonimmunosuppressive agents. In patients with generalized disease or whose disease is resistant to the treatments described above, systemic corticosteroids are preferred and effective. Adjuvant immunosuppressants are often combined with steroids for their steroid-sparing effect.

show abstract

Single‐nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine

Cited by 12 publications

References 50 publications

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

Pemphigus Vulgaris and Bullous Pemphigoid: Update on Diagnosis and Treatment

Contact Info

Product

Resources

About