Analyses and correlation of pathologic and ocular cutaneous changes in murine graft versus host disease

Robert B. Levy, Hazem M. Mousa, Casey O. Lightbourn, Eric J. Shiuey, David Latoni, Stephanie Duffort, Ryan Flynn, Jing Du, Henry Barreras, Michael Zaiken, Katelyn Paz, Bruce R. Blazar, Victor L. Perez

Research output: Contribution to journalArticlepeer-review

Abstract

Graft versus host disease (GVHD) is initiated by donor allo-reactive T cells activated against recipient antigens. Chronic GVHD (cGVHD) is characterized by immune responses that may resemble autoimmune features present in the scleroderma and Sjogren’s syndrome. Unfortunately, ocular involvement occurs in approximately 60–90% of patients with cGVHD following allo-hematopoietic stem cell transplants (aHSCT). Ocular GVHD (oGVHD) may affect vision due to ocular adnexa damage leading to dry eye and keratopathy. Several other compartments including the skin are major targets of GVHD effector pathways. Using mouse aHSCT models, the objective was to characterize cGVHD associated alterations in the eye and skin to assess for correlations between these two organs. The examination of multiple models of MHC-matched and MHC-mismatched aHSCT identified a correlation between ocular and cutaneous involvement accompanying cGVHD. Studies detected a “positive” correlation, i.e., when cGVHD-induced ocular alterations were observed, cutaneous compartment alterations were also observed. When no or minimal ocular signs were detected, no or minimal skin changes were observed. In total, these findings suggest underlying cGVHD-inducing pathological immune mechanisms may be shared between the eye and skin. Based on the present observations, we posit that when skin involvement is present in aHSCT patients with cGVHD, the evaluation of the ocular surface by an ophthalmologist could potentially be of value.

Original languageEnglish (US)
Article number184
JournalInternational journal of molecular sciences
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2022

Bibliographical note

Funding Information:
Funding: This work was supported by funds from the NIHRO1 EY024484-06, R01EY030283–01 (RL and VLP); R41AI149916-01, and SRA from Heat Biologics, Inc. (RL); Unrestricted grant from Research to Prevent Blindness Duke (VLP), Duke NIH-NEI P30-EY005722-35 (VLP); Stephen and Frances Foster Research Endowment (VLP), Sylvester Comprehensive Cancer Center. RL and the funder bodies were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Correlation
  • Cutaneous GVHD
  • Inflammation
  • Ocular GVHD
  • Ocular immune response
  • Pathology

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