A novel lateral flow immunoassay for the rapid detection of anti‐Dsg3 IgG serum autoantibodies in pemphigus vulgaris

Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.

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“…Recently, a novel lateral flow immunoassay (LFIA) was developed (82). It detects anti-Dsg 3 IgG in human sera.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to other diagnostic procedures, the assay is simpler and faster. LFIA was validated on a collection of 200 sera and showed a sensitivity and specificity of 78.1 and 97.1%, respectively (82).…”

Section: Introductionmentioning

confidence: 99%

Pemphigus: Current and Future Therapeutic Strategies

et al. 2019

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“…Pemphigus vulgaris (PV) is a severe tissue‐specific autoimmune bullous disease that causes blistering of the skin and mucous membranes. IgG autoantibodies that bind predominantly to the cadherin‐type adhesion molecule desmoglein (Dsg)3 have been implicated in PV 1,2 . These autoantibodies, although produced by B cells, are under the regulatory control of several lineages of T cells.…”

Section: Introductionmentioning

confidence: 99%

“…IgG autoantibodies that bind predominantly to the cadherin-type adhesion molecule desmoglein (Dsg)3 have been implicated in PV. 1,2 These autoantibodies, although produced by B cells, are under the regulatory control of several lineages of T cells. Studies have shown that T cells play an important role in the regulation of B-cell activation.…”

Section: Introductionmentioning

confidence: 99%

Functional inhibition of regulatory CD4+CD25+T cells in peripheral blood of patients with pemphigus vulgaris

Su¹,

Zhou²,

Ke³

et al. 2020

Clin. Exp. Dermatol.

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Summary Background Pemphigus vulgaris (PV) is a potentially life‐threatening autoimmune bullous disease affecting the skin and mucous membranes. Its pathogenic mechanism is still not fully understood. Regulatory T cells (Tregs) have been reported to play a significant role in regulating immune homeostasis in autoimmune disorders, such as PV. Aim To investigate the potential role of Tregs in the immunopathogenesis of PV. Methods We enrolled 15 patients with PV and 15 healthy controls (HCs). Peripheral blood samples were collected from all participants before treatment. This was followed by flow cytometric, real‐time reverse transcription PCR, and in vitro inhibition‐based functional assays to explore the immunopathogenesis of Tregs in PV. Results Our results showed no statistically significant differences in total CD4+CD25+ cells and CD4+CD25high cells. In addition, expression levels of FOXP3 mRNA and the corresponding FOXP3 protein remained unchanged in the patients with PV and the HCs. However, the in vitro suppressive activity of CD4+CD25+ T cells was impaired in patients with PV compared with HCs. Conclusions Our observations suggest that inhibition of suppressive activity of Treg cells may be involved in the pathogenesis of PV.

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“…Pemphigus is a life‐threatening autoimmune disease characterized by mucocutaneous blister formation which is mainly mediated by IgG autoantibodies formed against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and/or Dsg 1 . Nowadays, other pathogenic mechanisms such as apoptolysis, elevated proinflammatory cytokines and aberrant cell signalling pathways (p38MAPK‐signaling pathway) have been suggested in this regard .…”

Section: Introductionmentioning

confidence: 99%

The association betweenST18 gene polymorphism and severe pemphigus disease among Iranian population

Etesami

Hassan

Ghandi

et al. 2018

Experimental Dermatology

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Recently, ST18 polymorphism has played a role in increasing the risk of pemphigus among some populations such as Egyptian and Jewish. In addition, a variant within the ST18 promoter gene was shown to induce ST18 upregulation and cytokine secretion leading to keratinocyte susceptibility to anti-desmoglein antibodies. Thus, the present study aimed to assess the ST18 single nucleotide polymorphisms (SNP) relationship with pemphigus, disease severity and family history among Iranian population. A total of 111 pemphigus patients and 201 healthy controls were genotyped for three ST18 SNPs rs2304365, rs10504140 and rs4074067 by using TETRA-ARMS PCR method. The results indicated that risk allele A in rs2304365 was significantly higher in pemphigus patients, compared with the amount in the control group (OR = 2.43 CI = 1.49-3.975, P < 0.001). Thus, A allele represents a risk factor for pemphigus. Further, the patients carrying the risk allele had a more severe disease and a higher age of disease onset while no relationship was observed between the number of relapses and positive family history of pemphigus with the risk allele. Finally, dominant model was regarded as the strongest inheritance model for the associated risk. The present study confirmed the relationship between ST18 gene with pemphigus disease, a more severe disease, and a higher age of disease onset.

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A novel lateral flow immunoassay for the rapid detection of anti‐Dsg3 IgG serum autoantibodies in pemphigus vulgaris

Cited by 8 publications

References 27 publications

Pemphigus: Current and Future Therapeutic Strategies

Pemphigus: Current and Future Therapeutic Strategies

Functional inhibition of regulatory CD4+CD25+T cells in peripheral blood of patients with pemphigus vulgaris

The association betweenST18 gene polymorphism and severe pemphigus disease among Iranian population

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