Department of Dermatology and Allergology, Philipps-Universität Marburg, Marburg, Germany.
Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Front Immunol. 2021 Mar 25;12:569287. doi: 10.3389/fimmu.2021.569287. eCollection 2021.
Bullous pemphigoid (BP) is a prototypic autoimmune disorder of the elderly, characterized by serum IgG autoantibodies, namely anti-BP180 and anti-BP230, directed against components of the basal membrane zone that lead to sub-epidermal loss of adhesion. Pruritus may be indicative of a pre-clinical stage of BP, since a subset of these patients shows serum IgG autoantibodies against BP230 and/or BP180 while chronic pruritus is increasingly common in the elderly population and is associated with a variety of dermatoses. Clinical and experimental evidence further suggests that pruritus of the elderly may be linked to autoimmunity with loss of self-tolerance against cutaneous autoantigens. Thus, the objective of this study was to determine autoreactive T cell responses against BP180 in elderly patients in comparison to patients with BP. A total of 22 elderly patients with pruritic disorders, 34 patients with bullous or non-bullous BP and 34 age-matched healthy controls were included in this study. The level of anti-BP180 and anti-BP230 IgG serum autoantibodies, Bullous Pemphigoid Disease Area Index (BPDAI), and pruritus severity were assessed for all patients and controls. For characterization of the autoreactive T cell response, peripheral blood mononuclear cells were stimulated with recombinant BP180 proteins (NH- and COOH-terminal domains) and the frequencies of BP180-specific T cells producing interferon-γ, interleukin (IL)-5 or IL-17 were subsequently determined by ELISpot assay. Patients with BP showed a mixed Th1/Th2 response against BP180 while autoreactive Th1 cells were identified in a minor subset of elderly patients with pruritic disorders. Furthermore, our T cell characterization revealed that therapeutic application of topical clobetasol propionate ointment in BP patients significantly reduced peripheral blood BP180-specific T cells, along with clinically improved symptoms, strongly suggesting a systemic immunosuppressive effect of this treatment.
大疱性类天疱疮（BP）是一种典型的老年人自身免疫性疾病，其特征是血清 IgG 自身抗体，即抗 BP180 和抗 BP230，针对基底膜带的成分，导致表皮下附着力丧失。瘙痒可能表明 BP 的临床前阶段，因为这些患者中有一部分显示针对 BP230 和/或 BP180 的血清 IgG 自身抗体，而慢性瘙痒在老年人群中越来越常见，并与各种皮肤病有关。临床和实验证据进一步表明，老年人的瘙痒可能与自身免疫有关，对皮肤自身抗原失去自身耐受性。因此，本研究的目的是确定老年患者中针对 BP180 的自身反应性 T 细胞反应，并与 BP 患者进行比较。本研究共纳入 22 例瘙痒性疾病老年患者、34 例大疱性或非大疱性 BP 患者和 34 名年龄匹配的健康对照者。评估所有患者和对照者的抗 BP180 和抗 BP230 IgG 血清自身抗体、大疱性类天疱疮疾病面积指数（BPDAI）和瘙痒严重程度。为了表征自身反应性 T 细胞反应，用重组 BP180 蛋白（NH 和 COOH 末端结构域）刺激外周血单核细胞，随后通过 ELISpot 测定确定产生干扰素-γ、白细胞介素（IL）-5 或 IL-17 的 BP180 特异性 T 细胞的频率。BP 患者表现出针对 BP180 的混合 Th1/Th2 反应，而在瘙痒性疾病的老年患者的一小部分中鉴定出自身反应性 Th1 细胞。此外，我们的 T 细胞特征表明，BP 患者局部应用丙酸氯倍他索软膏治疗可显著减少外周血 BP180 特异性 T 细胞，同时临床症状改善，强烈表明该治疗具有全身性免疫抑制作用。
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