Highlights
- •Gene expression array revealed increase in the expression of
- •matrix metalloproteinases and tissue inhibitor of metalloproteinases in chronic cutaneous GVHD (cGVHD) compared to normal skin controls.
- •By immunostaining we observed increased TIMP3 levels in both lichenoid and sclerodemoid cutaneous cGVHD, mainly in dermal blood vessels.
Abstract
Background
Sclerodermoid graft-versus-host disease (GVHD) is the most severe form of chronic
GVHD (cGVHD) and represents a considerable therapeutic challenge. Due to the scarcity
of human studies on sclerodermoid cGVHD, the pathogenesis of this entity is not fully
understood.
Objective
To identify the differential expression of fibrosis-related genes in skin lesions
of human lichenoid and sclerodermoid cGVHD and to assess the expression of their corresponding
proteins.
Methods
PCR array analysis was performed on RNA extracted from three skin biopsies of sclerodermoid
cGVHD patients and three normal skin samples, for fibrosis-related gene expression
profiles followed by evaluation of their corresponding protein expressions. The expressions
of Tissue inhibitor of metalloproteinase 3 (TIMP3), matrix metalloproteinase 1 (MMP1),
TIMP1, and TIMP2 were further studied by immunohistochemistry. Demographic, clinical
and immunohistochemical parameters of the two cGVHD groups and the control group were
compared. The Pearson correlation coefficient was used to assess the correlation between
data among the study groups.
Results
We identified 44 upregulated and 14 downregulated genes in the skin samples of sclerodermoid
cGVHD compared to the control group. TIMP3 was positive in 13/21 biopsies of cGVHD
and in one biopsy of the control group. The average staining intensity was significantly
higher in the cGVHD group compared to the control group. TIMP3 was expressed mainly
in dermal blood vessels. cGVHD specimens with positive TIMP3 staining had a statistically
significantly higher total microvascular area than the negative specimens.
Conclusion
TIMP3 levels are increased in both subtypes of cGVHD and are associated with increased
dermal vascularity.
Keywords
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Article info
Publication history
Published online: May 13, 2022
Accepted:
May 10,
2022
Received in revised form:
April 27,
2022
Received:
December 12,
2021
Identification
Copyright
© 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
