Schwartz Rebekah R, Seiffert-Sinha Kristina, Sinha Animesh A
Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States.
Front Immunol. 2025 Jan 13;15:1500284. doi: 10.3389/fimmu.2024.1500284. eCollection 2024.
Autoimmune diseases (AID) are defined by immune dysregulation characterized by specific humoral and/or cell mediated responses directed against the body's own tissues. Cytokines in particular play a pivotal role in the pathogenesis of AID, with proinflammatory cytokines contributing to the initiation and propagation of autoimmune inflammation, whereas anti-inflammatory cytokines facilitate regression of inflammation and recovery from acute phases of the disease. Parallel work by our group evaluating a comprehensive set of pro- and anti-inflammatory serum cytokines in Pemphigus vulgaris (PV) as well as Alopecia areata (AA) uncovered a similar pattern of inheritance specific immune dysregulation in these two distinct autoimmune skin diseases. In AA, we found healthy control subjects who are blood related to AA patients exhibit the same cytokine dysregulation in Th1 and Th17 pathways as do patients with AA. In PV, patients as well as individuals who are healthy but yet carry certain PV-associated HLA alleles (termed here as HLA-matched controls) share a similar, but not fully overlapping pattern of cytokine expression that is distinct from control subjects who do not type for these HLA alleles. Specifically, PV patients as well as HLA-matched controls demonstrate immunological activation of several pro-inflammatory-, Th17-, Th2-pathway associated cytokines, and the chemokine IL-8. Thus, in both AA and PV, we reveal cytokine dysregulations that are linked to genetic background. The presence of disease promoting pathways in not only patients, but also genetically related, but healthy control individuals further evokes the novel hypothesis that there may be co-existing disease counteracting immune protective mechanisms at play in thwarting the threat of disease in genetically predisposed individuals who, despite harboring disease associated immune imbalances, remain healthy. Our data underscore the known tendency of AID to cluster in families and support the notion of the shared genetic/common cause hypothesis across multiple AID.
自身免疫性疾病（AID）是由免疫失调定义的，其特征是针对机体自身组织的特异性体液和/或细胞介导反应。细胞因子在AID的发病机制中尤其起着关键作用，促炎细胞因子促进自身免疫性炎症的起始和传播，而抗炎细胞因子则促进炎症消退和疾病急性期的恢复。我们小组的平行研究评估了寻常型天疱疮（PV）和斑秃（AA）中一组全面的促炎和抗炎血清细胞因子，发现这两种不同的自身免疫性皮肤病存在相似的遗传性特异性免疫失调模式。在AA中，我们发现与AA患者有血缘关系的健康对照者在Th1和Th17途径中表现出与AA患者相同的细胞因子失调。在PV中，患者以及健康但携带某些与PV相关的HLA等位基因的个体（在此称为HLA匹配对照）共享一种相似但不完全重叠的细胞因子表达模式，这与未检测这些HLA等位基因的对照受试者不同。具体而言，PV患者以及HLA匹配对照者表现出几种与促炎、Th17、Th2途径相关的细胞因子以及趋化因子IL-8的免疫激活。因此，在AA和PV中，我们都揭示了与遗传背景相关的细胞因子失调。不仅在患者中，而且在有遗传关系但健康的对照个体中都存在疾病促进途径，这进一步引发了一个新的假设，即在有遗传易感性的个体中，尽管存在与疾病相关的免疫失衡但仍保持健康，可能存在共同作用以对抗疾病威胁的疾病抵消免疫保护机制。我们的数据强调了AID在家族中聚集的已知倾向，并支持多种AID共享遗传/共同病因假说的观点。
