Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Department of Dermatology, College of Medicine, Howard University, Washington, District of Columbia, USA; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Invest Dermatol. 2023 Jan;143(1):57-66. doi: 10.1016/j.jid.2022.06.024. Epub 2022 Aug 4.
Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disorder characterized by abscess-like nodules and boils resulting in fistulas and tissue scarring. We previously reported evidence of an autoimmune signature in HS, characterized by enhanced neutrophil extracellular trap (NET) infiltration in HS skin lesions and dysregulation of the adaptive immune system characterized by the presence of autoantibodies. Timely removal of NETs is critical for tissue homeostasis to prevent a dysregulated generation of modified autoantigens and tissue damage. DNases 1 and 1L3 play important roles in proper NET removal. We tested the hypothesis that NETs in patients with HS are not effectively cleared owing to the presence of antibodies against DNase 1 and DNase 1L3. We report that HS serum poorly degraded NETs. Addition of exogenous DNase 1 restored NET degradation capabilities in a subset of HS samples. DNase 1 activity was significantly decreased in HS sera. Anti‒DNase 1 and ‒DNase 1L3 antibodies were detected in serum samples and skin lesions from patients with HS. Purified IgGs from HS decreased DNase 1 activity and NET degradation. Taken together, this identification of neutralizing antibodies against nucleases in HS expands the understanding of the pathogenesis of this disease to support an autoimmune mechanism in its underlying pathogenesis.
化脓性汗腺炎（HS）是一种使人衰弱的炎症性皮肤病，其特征是出现脓肿样结节和疖子，导致瘘管和组织瘢痕。我们之前报道了 HS 中存在自身免疫特征的证据，其特征是 HS 皮肤损伤中中性粒细胞胞外陷阱（NET）的浸润增强，以及适应性免疫系统失调，表现为自身抗体的存在。及时清除 NET 对于组织稳态至关重要，可防止修饰后的自身抗原的失调产生和组织损伤。DNase 1 和 1L3 在适当的 NET 清除中发挥重要作用。我们检验了这样一个假说，即由于存在针对 DNase 1 和 DNase 1L3 的抗体，HS 患者的 NET 无法被有效清除。我们报告称，HS 血清不能有效地降解 NET。在一部分 HS 样本中添加外源性的 DNase 1 可恢复 NET 降解能力。HS 血清中的 DNase 1 活性显著降低。HS 患者的血清和皮肤损伤样本中检测到抗‒DNase 1 和抗‒DNase 1L3 抗体。从 HS 中纯化的 IgG 降低了 DNase 1 活性和 NET 降解。总之，这项对 HS 中核酶的中和抗体的鉴定扩展了对该疾病发病机制的理解，支持其潜在发病机制中的自身免疫机制。
