Impact of HLA alloimmunization on clinical outcomes of severe aplastic anemia treated with immunosuppressive therapy

Immune aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… (iAA) frequently results in transfusion dependence on platelets and packed red blood cells, increasing the risk for complications. The most common immune-mediated cause for platelet platelet: The smallest type of blood cell. Platelets help the blood to clot and stop bleeding. Also called a thrombocyte. -transfusion refractoriness is alloimmunization with HLA HLA: See human leukocyte antigen. antibody (Ab) to nonself class I antigens. The clinical impact of the HLA alloimmunization has not been well studied in patients with iAA. We investigated the clinical relevance of HLA alloimmunization in our large cohort of patients with iAA from 5 prospective trials and correlated with disease outcomes. Of 444 patients with severe AA treated with immunosuppressive therapy immunosuppressive therapy: Immunosuppressive drug therapy lowers your body's immune response. This prevents your immune system from attacking your bone marrow, allowing bone marrow stem cells to grow, which raises blood counts. For older patients with acquired aplastic anemia, immunosuppressive drug therapy is the… (IST), 99 (22%) had HLA alloimmunization. The presence of HLA Ab was associated with shorter overall survival, reduced responses to IST and higher risk of clonal evolution. Our data suggest that HLA alloimmunization is a marker of disease outcome. Furthermore, using single-cell RNA sequencing, we show enhanced activation of both complement-mediated pathways and the adaptive immune system in alloimmunized patients, indicating an interconnection between immune compartments.