Myelodysplastic syndromes are clonal hematopoietic stem cell disorders, in which the immune system plays a substantial pathogenetic role. Patients manifest frequent infections, mainly attributed to neutropenia, but sometimes opportunistic pathogens are isolated in non-neutropenic patients. They also exhibit autoimmune diseases or syndromes with a background of immune activation and various “abnormalities” of T-lymphocytes, B-lymphocytes, and NK cells. The most typical profile includes reduced total T lymphocytes (mainly CD4+ helper T-cells, resulting in decrease or inversion of the CD4/CD8 cell ratio) and impaired NK cell function. Many TH1 direction cytokines, and particularly sIL-2R, IL-6, and TNF-α are usually found increased in the serum and bone marrow, which have been strongly associated with advanced disease, anemia, and other disease-related features. Clonal origin of lymphocytes has been confirmed only in few cases. Mixed lymphocyte cultures and genomic assays have shown severely impaired immunoregulatory abnormalities, probably induced by the hematopoietic cells. In a minority of patients, immune activation is capable to prevent or delay clonal expansion, but these patients have more profound hematopoietic impairment. Immunosuppressive treatment may not only relieve the autoimmune manifestations but also improve hematopoiesis. However, this kind of treatment is not well tolerated, is associated with severe infections, and in some cases may enhance AML evolution.
Part of the book: Myelodysplastic Syndromes