High multi-cytokine levels are not a predictive marker of alloimmunization in transfused sickle cell disease patients

• We assessed plasma levels of 10 cytokines in multiply transfused children with sickle cell disease.
• Twelve out of 83 clinically steady state patients had high levels of all cytokines tested.
• We evaluated the rates of production of antibodies specific for donor red blood cells.
• Patients with high cytokine levels had indistinguishable rates of antibody production.
• High cytokine levels are not predictive of past/future anti-red blood cell antibodies.

Patients with sickle cell disease (SCD) receive multiple red blood cell (RBC) transfusions for both prevention of and therapy for disease-related complications. In some patients, transfusion results in development of both allo- and auto-antibodies to RBC antigens. What precipitates the antibody formation is currently unclear. It has been hypothesized that a pro-inflammatory state preceding the therapeutic transfusion may be a predisposing factor. Plasma levels of ten cytokines were evaluated upon recruitment to the study of 83 children with SCD undergoing therapeutic RBC transfusions. The levels of cytokines were correlated with development of anti-RBC antibodies prior, or during seven years post recruitment. Twelve subjects displayed significantly higher levels of all cytokines examined, with pro-, as well as anti-inflammatory properties. Surprisingly, the elevated levels of cytokines were preferentially found in patients without anti-RBC allo- and/or auto-antibodies. Further, presence of high cytokine levels was not predictive of anti-RBC antibody development during the subsequent seven year follow up. These data suggest that the increased concentration of multiple cytokines is not a biomarker of either the presence of or susceptibility to the development of RBC alloimmunization.