Chronic Graft-Versus-Host Disease
Chronic GVHD typically develops >3 months post-transplant, although histologic and clinical manifestations can be present earlier. Chronic GVHD differs from acute GVHD in its distribution of target organs and clinical presentation. T-lymphocytes are likely involved in the pathogenesis of both types, but in contrast to acute GVHD, in which T-cells respond to alloantigens, T-cells in chronic GVHD react in an autoimmune fashion against histocompatibility alloantigens of the host (public determinant of MHC class II molecules). These T-cells produce abnormal patterns of cytokines and can stimulate the production of collagen by fibroblasts. In long-term stable survivors without chronic GVHD, alloimmunity seems to be blocked by specific suppressor cells which usually are not found in patients with chronic GVHD. It has also been postulated that the establishment of tolerance requires a functioning thymus. Since thymus function can be impaired as a consequence of chemo/radiotherapy or acute GVHD, the lack of thymus function may hamper the development of specific suppressor cells capable of mediating stable graft-host tolerance, and/or delete autoreactive T-cells. The donor-host directed alloaggression may be only an initial event leading to autoimmune symptoms, impaired immune reconstitution and infections and it is likely that the release of certain cytokines contributes to the manifestation of chronic GVHD.
KeywordsAcute GVHD Chronic GVHD Chronic Graft Sicca Syndrome Thymus Function
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