**7.3 Haemolytic reaction associated with the "bystander immune cytolysis"**

The haemolytic transfusion reactions may have a different immunological origin than the reactions of antibodies in the recipient's blood and the antigen present on the donor's blood cells. This additional mechanism occurs when recipient's red blood cells are destroyed by a reaction called "bystander immune cytolysis". It is defined as the immunological destruction of red blood cells by antibodies whose specificity corresponds to antigens found on other cells/blood cells (e.g. HLA antigens found on leukocytes and plasma proteins), while red blood cells are only close to this immunological "confusion" [56]. They are destroyed by the complement system, although they did not participate directly in the antigen-antibody reaction. One of the reasons for this haemolytic reaction is the binding of the C567 complement complex, activated in an immune reaction, to the membrane of red blood cells not participating in the reaction but located in the vicinity [56]. Blood cells are destroyed as a result of the activation of the binding of the remaining components of C8 and C9 complement and the formation of the MAC complex on the blood cells [56]. The mechanism of "bystander" haemolysis is similar to the destruction of blood cells in patients with paroxysmal nocturnal haemoglobinuria [57, 58]. A characteristic feature of the cell membrane of these blood cells is the lack or weak expression of the CD55 (DAF) and CD 59 (MIRL) proteins, which are complement inhibitors. This makes the subject more susceptible to haemolysis. It was found that

when red blood cells became the "bystander" of leukocyte reactions and antibodies directed to them, they underwent haemolysis. The reaction of anti-HLA antibodies with leucocytes caused complement activation, which resulted in haemolysis of the patient's red blood cells sensitive to the complement [59]. It is noteworthy that in patients with a haemolytic reaction associated with the immune cytolysis of the "bystander" not only transfused red blood cells but also autologous blood cells of the patient were destroyed.
