TY - JOUR
T1 - Autoantibodies Present in Hidradenitis Suppurativa Correlate with Disease Severity and Promote the Release of Proinflammatory Cytokines in Macrophages
AU - Carmona-Rivera, Carmelo
AU - O'Neil, Liam J.
AU - Patino-Martinez, Eduardo
AU - Shipman, William D.
AU - Zhu, Chengsong
AU - Li, Quan Zhen
AU - Kerns, Michelle L.
AU - Barnes, Leandra A.
AU - Caffrey, Julie A.
AU - Kang, Sewon
AU - Kaplan, Mariana J.
AU - Okoye, Ginette A.
AU - Byrd, Angel S.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti–human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.
AB - Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti–human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.
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U2 - 10.1016/j.jid.2021.07.187
DO - 10.1016/j.jid.2021.07.187
M3 - Article
C2 - 34606886
AN - SCOPUS:85118234539
SN - 0022-202X
VL - 142
SP - 924
EP - 935
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -