Irregular antibodies in no hemolytic autoimmune diseases are able to induce erythrophagocytosis

Abstract

Irregular antibodies are produced by alloimmunization because of pregnancies or blood transfusions. They are called "irregular" due to target erythrocyte antigens from "rare blood systems," those different from the ABO system. Irregular antibodies have been widely investigated in immunohematology since their presence in blood donors may lead to difficulties in blood typing and in blood cross-matching, or to induce hemolytic transfusion reactions. Nevertheless, their incidence and participation in the physiopathology of autoimmune diseases have not been thoroughly studied. In this work, we analyzed the presence and pro-hemolytic capabilities of irregular antibodies in patients with different autoimmune diseases lacking signs of hemolytic anemia, in comparison with healthy multiparous women. Five of 141 autoimmune patients (3.5 %) and two of 77 multiparous women (2.6 %) were positive. Although frequency was relatively low and similar in both populations, the targeted antigens were Kell (k, Kp, Js) and Luth (Lu) in multiparous women, and the same plus Duffy (Fy), Kidd (Jk) and MNS (M, s) in autoimmune patients. Irregular antibodies from autoimmune patients did not induce complement-mediated hemolysis (intravascular), but they were able to induce macrophages-mediated phagocytosis (extravascular hemolysis) in vitro. It is the first approach exploring the presence of irregular antibodies associated with the loss of immune tolerance and demonstrating their hemolytic potential in autoimmune patients without hemolytic manifestations. The presence of irregular antibodies targeted to Duffy (Fya), Kidd (Jka) and MNS (M, s) antigens only in autoimmune patients suggests a loss of immune tolerance to these erythrocyte antigens.

Red‐blood‐cell alloimmunization and prophylactic antigen matching for transfusion in patients with warm autoantibodies

“…In a large cohort study, alloimmunization was found to be more common in females (2·38%) than males (1·68%, P ≤ 0·0001) [23]. AIHA can be precipitated by previous viral infection and autoimmune diseases, both of which can be associated with loss of immune tolerance [24]. A study of alloantibodies in a cohort of patients with autoimmune disease found that autoantibodies appeared to have IgG and IgM classes of antibodies, suggestive active immune activity, and may cross‐react with similar epitopes in other patients with alloantibodies to Kell and Lutheran [24,25].…”

“…AIHA can be precipitated by previous viral infection and autoimmune diseases, both of which can be associated with loss of immune tolerance [24]. A study of alloantibodies in a cohort of patients with autoimmune disease found that autoantibodies appeared to have IgG and IgM classes of antibodies, suggestive active immune activity, and may cross‐react with similar epitopes in other patients with alloantibodies to Kell and Lutheran [24,25]. Thus, a hypothesis could be that in patients with a diagnosis of AIHA or suspected AIHA, the PAM approach should be used instead of using PAM for all patients with WAA, given the possibility that the underlying mechanism for WAA alone appears to be tilted towards disease association.…”

Biomarkers and Pathogenic Mechanisms in Autoimmunity

“…In a presented study, the authors show that these antibodies are widely investigated in immunohematology since their presence in blood donors may lead to difficulties in blood typing and in blood crossmatching, or to induce hemolytic transfusion reactions. They also show that these antibodies do not induce hemolysis in vitro but enhance macrophage-mediated phagocytosis of erythrocytes [11]. Idiopathic hypertrophic pachymeningitis (IHP), characterized by the thickening of cerebral or spinal dura mater, is considered to be of inflammatory origin.…”