Multifactorial etiology of rhEPO-induced PRCA. The complex interaction between various product-related and patient-related factors, including the formation of rhEPO aggregates, antigenic processing, and presentation of immunodominant epitopes by antigen-presenting cells, presence of specific HLA class II proteins capable of binding certain rhEPO peptides, and potentially other characteristics of EPO, together influence the immune response to rhEPO after subcutaneous injection, leading to rare cases of PRCA in susceptible patients.