Discovery of IgG4 Anti‐Gliadin Autoantibody as a Potential Biomarker of Psoriasis Using an Autoantigen Array

Abstract

Purpose Psoriasis is a complex immunological skin disease. However, whether humoral autoimmunity is involved in the pathogenesis of psoriasis remains unclear. The aim is to determine if there are autoantibodies associated with disease activity of psoriasis. Experimental Design A novel autoantigen array harboring 75 antigens is developed to discover autoantibodies in the serum of psoriasis patients (N = 12) compared to healthy controls (N = 12). Validation studies are performed in a larger cohort of psoriasis patients (N = 73) and healthy controls (N = 75) together with atopic dermatitis as disease controls (N = 10). Results The screening results demonstrate that immunoglobulin G4 (IgG4) anti‐gliadin autoantibodies are significantly elevated in the serum of psoriasis patients, compared to healthy controls. Receiver operating characteristic (ROC) analysis indicates that IgG4 anti‐gliadin autoantibody levels can clearly discriminate psoriasis patients from healthy controls with an AUC of 0.98 (p < 0.001). Also, IgG4 anti‐gliadin autoantibody can reflect disease severity with the psoriasis area severity index score in a subpopulation of psoriasis patients. Conclusions and Clinical Relevance These results suggest that IgG4 anti‐gliadin autoantibody may be a disease marker of psoriasis, and it may be useful in clinical diagnostics and disease monitoring of psoriasis. Clinical Relevance This work represents a relatively comprehensive screening of autoantibodies, that is, IgG4 autoantibodies in psoriasis using an in‐house autoantigen array. This novel proteomic platform may be useful in clinical screening of IgG type or IgG4 subtype autoantibodies in psoriasis patients for disease monitoring or drug responses. Particularly, IgG4 anti‐gliadin autoantibody, as a new potential disease marker of psoriasis, may be useful in clinical diagnostics or prognostics of related immunological disorders.

An Aptamer-Array-Based Sample-to-Answer Biosensor for Ochratoxin A Detection via Fluorescence Resonance Energy Transfer

“…Streptavidin was diluted with PBS buffer, and then 500 picoliters of the sample was printed onto an epoxycoated slide with a microarray printing robot (sciFLEXARRAYER S3; Scienion) at 25 • C in an atmosphere of 60% humidity, as described previously [29]. The array detection procedure was according to our previous work [30][31][32][33]. The fluorescence signal on the chip was scanned and analyzed with a GenePix 4000B scanner and a Genepix Pro 7 software (Molecular Devices, San Jose, CA, USA).…”

Current Evidence on the Efficacy of Gluten-Free Diets in Multiple Sclerosis, Psoriasis, Type 1 Diabetes and Autoimmune Thyroid Diseases

“…According to a publication from 2020 that tested for antibodies against an array of 75 antigens, IgG4 antigliadin antibodies were the only antibodies to be elevated in the sera of 12 patients with severe psoriasis (PASI > 30) [ 81 ]. IgG4 antigliadin antibodies were not present in sera from 12 HCs.…”

“…Later validation, using a cohort with 73 psoriasis patients and 75 HCs, resulted in an area under the curve of 0.98 ( p < 0.001) in the receiver operating characteristic (ROC) analysis, suggesting that IgG4 antigliadin antibodies could potentially function as a diagnostic biomarker for psoriasis. For a subgroup of patients with the highest levels of anti-gliadin IgG4, there was a significant correlation between antibody levels and PASI scores (r = 0.65, p < 0.001) [ 81 ].…”

Current knowledge on autoantigens and autoantibodies in psoriasis

“…However, their roles in inflammation need to be clarified in future studies. Recently, a multiplex autoantigen array harbouring 75 antigens was conducted with the purpose of screening for autoantibodies in psoriasis 50 . Interestingly, the authors found that anti‐gliadin IgG4 autoantibodies were significantly elevated in the serum of psoriasis patients, whereas hnRNP‐A1 and ADAMTSL5 autoantibodies could not discriminate psoriasis patients from controls.…”

“…Interestingly, the authors found that anti‐gliadin IgG4 autoantibodies were significantly elevated in the serum of psoriasis patients, whereas hnRNP‐A1 and ADAMTSL5 autoantibodies could not discriminate psoriasis patients from controls. Despite not having data on patients’ diet (gluten‐free or not), this raises the question whether gliadin, a component of gluten present in wheat, could be a trigger for autoimmune responses 50 …”