Dataset Information

Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease.

ABSTRACT: Allogeneic hematopoietic stem cell transplant (allo-HSCT) is often used to treat acute leukemia or defects of hematopoiesis. Its widespread use is hampered by graft-vs.-host disease (GVHD), which has high morbidity and mortality in both acute and chronic subtypes. Chronic GVHD (cGVHD) occurs most frequently in skin and often is characterized by pathogenic fibrosis. Mast cells (MCs) are known to be involved in the pathogenesis of other fibrotic diseases. In a murine model of cGVHD after allo-HSCT, C57BL/6J recipients of allogeneic LP/J donor cells develop sclerodermatous dermal cGVHD which is significantly decreased in mast cell-deficient B6.Cg-KitW-sh/HNihrJaeBsmGlliJ recipients. The presence of MCs is associated with fibrosis, chemokine production, and recruitment of GVHD effector cells to the skin. Chemokine production by MCs is blocked by drugs used to treat cGVHD. The importance of MCs in skin cGVHD is mirrored by increased MCs in the skin of patients with dermal cGVHD. We show for the first time a role for MCs in skin cGVHD that may be targetable for preventive and therapeutic intervention in this disease.

SUBMITTER: Strattan E

PROVIDER: S-EPMC6813249 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease.

Strattan Ethan E Palaniyandi Senthilnathan S Kumari Reena R Du Jing J Hakim Natalya N Huang Timothy T Kesler Melissa V MV Jennings C Darrell CD Sturgill Jamie L JL Hildebrandt Gerhard C GC

Frontiers in immunology 20191018

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is often used to treat acute leukemia or defects of hematopoiesis. Its widespread use is hampered by graft-vs.-host disease (GVHD), which has high morbidity and mortality in both acute and chronic subtypes. Chronic GVHD (cGVHD) occurs most frequently in skin and often is characterized by pathogenic fibrosis. Mast cells (MCs) are known to be involved in the pathogenesis of other fibrotic diseases. In a murine model of cGVHD after allo-HSCT ...[more]

PMID: 31681336

Similar Datasets

Project description:ImportanceCutaneous manifestations of chronic graft-vs-host disease (GvHD) are highly variable and may recapitulate well-characterized autoimmune diseases, including systemic sclerosis and Sjögren syndrome. However, vitiligo and alopecia areata (AA) have not been well characterized in the chronic GvHD setting.ObjectiveTo determine laboratory markers, transplant-related factors, and other systemic manifestations associated with vitiligo and/or AA in patients with chronic GvHD.Design, setting, and participantsA cross-sectional, retrospective study conducted by the National Institutes of Health (NIH) of 282 adult and pediatric patients with chronic GvHD seen under the NIH natural history protocol between 2004 and 2013.Main outcomes and measuresDemographic, clinical, and laboratory data, including measures of 11 antibodies, were included in the analysis. Patients with vitiligo and/or AA were identified from dermatologist documentation and photographic evidence. Univariate and multivariable logistic regression analyses were used to determine risk factors for vitiligo and AA development.ResultsFifteen (5.3%) of 282 patients demonstrated vitiligo (14 of 282; 4.9%) and/or AA (2 of 282; 0.7%) (1 patient had both vitiligo and AA). Univariate analysis identified female donor to male recipient sex mismatch (P = .003), positive test results for anticardiolipin (ACA) IgG (P = .03) or antiparietal antibody (P = .049), elevated CD19 level (P = .045), and normal or elevated IgG level (P = .02) as risk factors for vitiligo or AA. Female donor to male recipient sex mismatch (P = .003) and positive findings for ACA-IgG (P = .01) retained significance in the multivariable analysis.Conclusions and relevanceFemale donor and female donor to male recipient sex mismatch, in particular, are significantly associated with the development of vitiligo and/or AA. Further studies are needed to explore transplant-related risk factors that may lead to better understanding of the pathomechanisms of chronic GvHD.

Dataset Information

Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease.

Publications

Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets