Erythrocyte membrane proteins reactive with human (warm-reacting) anti-red cell autoantibodies.

Abstract

Immunoglobulin G (IgG) autoantibodies of 20 patients with autoimmune hemolytic anemia (AHA) were used in immunoaffinity assays with surface-radioiodinated human red was not seen in the absence of p34, and both proteins are likely to be members of the Rh family. Indeed, a 34-kD polypeptide band and 37-55-kD polydisperse "smear," isolated concurrently from the same labeled RBCs by IgG allo-anti-e, were indistinguishable from their autoantibody-isolated counterparts and may well be the same protein identified at different epitopes by the auto-and allo-antibodies. Individual AHA patients' autoantibodies isolated p34 and gp37-55, alone or in combination with band 3 (nine cases); strong band 3 alone (five cases); and combinations of band 3 with GPA (six cases). The autoantibodies of three additional patients whose AHA had been induced by a-methyldopa also isolated p34 and gp37-55. (J. Clin. Invest. 1993. 91:1672-1680

Interleukin-10–mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen

“…Although compelling evidence has accumulated that Tr cells secreting inhibitory cytokine are important in the control of pathogenic immune responses in animal models, 7-14 the cells' existence and character in human autoimmune disease previously have been unclear. The work was facilitated in AIHA because, unlike many other human autoimmune conditions, the unequivocal identification of the major RBC autoantigens 21,22,29 has enabled the relevant Th-cell responses to be studied in detail. The major findings are that IL-10-secreting Tr cells responsive to a major RBC autoantigen, the RhD protein, are detectable in the blood of patients with AIHA, and they specifically suppress proliferative Th1 responses elicited by the antigen in vitro, and they predominantly recognize peptides containing naturally processed epitopes.…”

“…20 The disease can be classified according to the temperature reactivity and class of the autoantibodies 20 : "warm" IgG antibodies are the most common, have optimal affinity at 37°C, and promote RBC destruction by splenic macrophage phagocytosis and/or complement-mediated lysis. 20 In the majority of patients, warm antibodies are specific for the Rh protein complex, 21,22 which also expresses important blood groups. Current therapy for warmtype AIHA is reliant on corticosteroids, often given over a long period of time, with transfusion to treat any life-threatening hemolytic crises, and other immunosuppressive drugs or splenectomy used in refractory or relapsing cases.…”

Chronic Lymphocytic Leukemia Cells Bind and Present the Erythrocyte Protein Band 3: Possible Role as Initiators of Autoimmune Hemolytic Anemia

“…The initial assumption was that the neoplastic cells themselves were responsible for autoantibody production. This hypothesis was later discarded after Ab analysis from erythrocyte eluates showed a polyclonal nature and found no differences from those in AHA secondary to systemic lupus erythematosus (7), an autoimmune systemic disease in which no abnormal B cell clone has been described. Therefore, anti-erythrocyte Abs, which are of the IgG isotype and exhibit affinity maturation, must be produced by normal, autoreactive B cells in a T cell-dependent manner.…”

“…However, it is unclear how CLL cells could take up and process this protein considering that they are not efficient at fluid-phase endocytosis nor they express Rh-specific BCR (10,11). Besides the Rh group, the anion exchanger also known as band 3 (B3) (12), is a frequent targeted Ag both in human and murine AHA (7,(13)(14)(15)(16). When modified on Plasmodium-infected erythrocytes, B3 can be recognized by the scavenger receptor CD36 present on the monocyte membrane (17,18).…”

Role of naturally occuring autoantibodies in senescence of normal and ATP depleted goat erythrocytes

“…Results obtained by the immunoblotting experiments performed using membranes of control and ATP depleted red The results obtained in this study are in agreement with those obtained by Wegner (22) and Halbhuber (23), who showed that ATP depleted human RBC bound substantial amounts of autologous antibody. Recent studies aimed at modeling the senescence pathway in vitro of human RBC have shown that autologous antibodies bind to band 3 on immunoblots (24,25). It is probable that Ca 2+ mediated effects thus seem to be replaced by alternative mechanism in goats.…”