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HYPOTHESIS AND THEORY article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1500284
This article is part of the Research Topic Cytokine Network Dynamics: Influence on Autoimmune Disorders and Cancer Therapy View all 3 articles

Healthy Individuals Genetically At-Risk for the Development of Pemphigus vulgaris or Alopecia areata Share Disease-like Cytokine Dysregulation

Provisionally accepted
Rebekah R Schwartz Rebekah R Schwartz Kristina Seiffert-Sinha Kristina Seiffert-Sinha Animesh A Sinha Animesh A Sinha *
  • Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, United States

The final, formatted version of the article will be published soon.

    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.

    Keywords: Pemphigus, Alopecia, cytokine, HLA, Th17, th2, Autoimmunity

    Received: 23 Sep 2024; Accepted: 13 Dec 2024.

    Copyright: © 2024 Schwartz, Seiffert-Sinha and Sinha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Animesh A Sinha, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.