Yulin Yuan1, Jingyi Qiu2, Zuan-Tao Lin2, Wen Li3, Christopher Haley4, Uyen Ngoc Mui4, Jing Ning3, Stephen K Tyring5, Tianfu Wu2. 1. People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China, and University of Houston, Houston, Texas. 2. University of Houston, Houston, Texas. 3. University of Texas MD Anderson Cancer Center, Houston. 4. Center for Clinical Studies, Webster, Texas. 5. Center for Clinical Studies, Webster, Texas, and University of Texas Health Science Center at Houston.
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.
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 psoriasispatients 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.
Authors: Di Yan; Johann E Gudjonsson; Stephanie Le; Emanual Maverakis; Olesya Plazyo; Christopher Ritchlin; Jose U Scher; Roopesh Singh; Nicole L Ward; Stacie Bell; Wilson Liao Journal: J Invest Dermatol Date: 2021-07-22 Impact factor: 8.551
Authors: Oliver S Burren; Guillermo Reales; Limy Wong; John Bowes; James C Lee; Anne Barton; Paul A Lyons; Kenneth G C Smith; Wendy Thomson; Paul D W Kirk; Chris Wallace Journal: Genome Med Date: 2020-11-25 Impact factor: 11.117
Authors: Michelle L M Mulder; Tamara W van Hal; Mark H Wenink; Hans J P M Koenen; Frank H J van den Hoogen; Elke M G J de Jong; Juul M P A van den Reek; Johanna E Vriezekolk Journal: Arthritis Res Ther Date: 2021-06-14 Impact factor: 5.156