muramidase and Anemia--Sickle-Cell

Topics: Agammaglobulinemia; Anemia, Sickle Cell; Chemotaxis; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Immunity, Cellular; Immunoglobulin E; Immunologic Deficiency Syndromes; Infections; Job Syndrome; Lactoferrin; Leukocytes; Male; Muramidase; Opsonin Proteins; Peroxidase; Phagocytes; Phagocytosis; Staphylococcus

Increased rates of red blood cell (RBC) alloimmunization in patients with sickle cell disease may be due to transfusion frequency, genetic predisposition, or immune dysregulation. To test the hypothesis that sickle cell pathophysiology influences RBC alloimmunization, we utilized two transgenic mouse models of sickle cell disease.. Transgenic sickle mice, which express human α and β(S) globin, were transfused with fresh or 14-day-stored RBCs containing the HOD (hen egg lysozyme, ovalbumin, and human Duffy(b) ) antigen; some recipients were inflamed with poly(I : C) before transfusion. Anti-HOD alloantibody responses were subsequently measured by enzyme-linked immunosorbent assay and flow crossmatch; a cohort of recipients had posttransfusion serum cytokines measured by bead array.. Both Berkeley and Townes homozygous (SS) and heterozygous (AS) mice had similar rates and magnitude of anti-HOD RBC alloimmunization after fresh HOD RBC transfusion compared with control animals; under no tested condition did homozygous SS recipients make higher levels of alloantibodies than control animals. Unexpectedly, homozygous SS recipients had blunted cytokine responses and lower levels of anti-HOD alloantibodies after transfusion of 14-day stored RBCs, compared with control animals.. In sum, homozygous β(S) expression and the ensuing disease state are not alone sufficient to enhance RBC alloimmunization to transfused HOD RBCs in two distinct humanized murine models of sickle cell disease under the conditions examined. These data suggest that other factors may contribute to the high rates of RBC alloimmunization observed in humans with sickle cell disease.

Topics: Anemia, Sickle Cell; Animals; Disease Models, Animal; Erythrocyte Transfusion; Erythrocytes; Humans; Immunization; Isoantibodies; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Muramidase

Topics: Anemia, Sickle Cell; Animals; Erythrocyte Transfusion; Erythrocytes; Humans; Isoantibodies; Muramidase

Eight patients with homozygous sickle cell anemia, 15 heterozygotes, and eight control individuals were investigated with respect to plasma concentrations of the inflammatory markers lysozyme and myeloperoxidase and the complement activation marker C3d. The patients showed significantly increased levels of myeloperoxidase and C3d, but not lysozyme, compared with the heterozygotes and the controls. The heterozygotes were also significantly different from the controls with regard to C3d concentration. The concentrations of myeloperoxidase and C3d in plasma showed a significant inverse correlation with the hemoglobin concentration. Myeloperoxidase and C3d showed a significant positive correlation. This suggests a role for the neutrophil and the complement system in the pathophysiology of sickle cell disease.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Child; Child, Preschool; Complement C3d; Hemoglobins; Humans; Infant; Muramidase; Neutrophils; Peroxidase; Sickle Cell Trait

Topics: Anemia, Sickle Cell; Erythrocytes, Abnormal; Humans; Muramidase