Identification of Novel Autoantibodies Associated With Psoriatic Arthritis

Abstract

Objective. The autoimmune etiology in psoriasis remains to be clarified. We therefore undertook this study to identify novel pathogenic autoantigens and autoantibodies in patients with psoriasis, with the aim of shedding light on the molecular and cellular basis of the pathogenesis of psoriasis and psoriatic arthritis (PsA).Methods. In this study, we developed an autoantigen array system that harbors a variety of antigens, including typical autoantigens in rheumatic diseases as well as skin antigens, inflammatory mediators, and putative autoantigens in psoriasis. Serum samples from patients with psoriasis (n = 73) were used to interrogate the antigens on the array. In addition, enzyme-linked immunosorbent assays of individual autoantibodies were used in validation studies.Results. Levels of several autoantibodies were found to be elevated in the serum of patients with psoriasis compared to healthy controls; in particular, IgG autoantibodies against 2 novel antigens, LL-37 and ADAMTS-L5, were significantly increased in patients with psoriasis. Importantly, serum levels of IgG autoantibodies against LL-37 and ADAMTS-L5 were correlated with the Psoriasis Area and Severity Index, and reflected disease progression in longitudinally collected serum samples from patients with psoriasis. Importantly, both anti-ADAMTS-L5 and anti-LL-37 autoantibody levels were also significantly elevated in psoriasis patients with PsA compared to those without PsA, suggesting that these molecules may be involved in the pathogenesis of PsA.Conclusion. Our findings indicate that these identified autoantibodies may be useful biomarkers and may serve as therapeutic targets in psoriasis and PsA.

Informed dimension reduction of clinically-related genome-wide association summary data characterises cross-trait axes of genetic risk

“…34 Weaker but significant association of Psoriatic arthritis (PsA) among the other seropositive IMD is also consistent with a recent report of novel pathogenic antibodies in PsA. 35 Our basis offered alternative viewpoints of this collection of diseases. For example, significant IMD on the MIG/IP-10-associated PC3 included both 'seropositive' and 'seronegative' diseases, although not atopy, while all three groups were represented on the eosinophil associated PC13.…”

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

“…To build the autoantigen array, antigens were purchased from commercial vendors, and the optimal concentration of each antigen was selected from a serially diluted antigen gradient (1:2), as detailed in the recently published paper . The antigen concentrations were as shown in Table .…”

“…Between antigen arrays, total fluorescence intensity of each array was used to normalize the data in each array. Briefly, the microarray slides were prewashed using PBS and double‐deionized water, then the antigens were printed onto proper array slides using sciFLEXARRAYER S3 system . First, the Super G blocking buffer (Sigma, Grace Bio‐Labs) was used to block the printed slides overnight at 4 °C.…”

“…In recent studies, cathelicidin (LL‐37), ADAMTSL5, and PLA2G4D were implicated as potential autoantigens in psoriasis . Interestingly, IgG anti‐LL37, anti‐ADAMTSL5 antibodies were detected in psoriatic arthritis (PsA) patients.…”

Thinking Positive in Spondyloarthritis

“…In this issue of Arthritis & Rheumatology , Yuan and colleagues report a similar approach to autoantibody detection in patients with psoriasis . The study was limited in numbers to 73 patients with psoriasis, 10 control patients with skin disease (atopic dermatitis), 7 control patients with autoimmune disease (systemic lupus erythematosus [SLE]), and 30 healthy controls.…”