Autoimmune Hemolytic Anemia Associated Exclusively with IgA of Rh Specificity

Abstract

A nine-year-old boy had typical clinical, hematologic and blood group serologic findings of autoimmune hemolytic anemia except for one important exception; with most commercially available broad spectrum anti-human sera the direct antiglobulin tests were negative. With reagents prepared in the laboratory which were found to be relatively less potent in and anti-IgG and IgM activity but which utilize a short period of incubation after mixing with the washed cells, the tests were all clearly positive. If incubation were employed with the commercial reagents, the tests were positive. Further studies showed that the patient's cells were coated exclusively with IgA and that a commercial reagent, although potent in anti-IgG and anti-IgM, was relatively deficient in anti-IgA. It is proposed that incubation compensates for the latter and is cautioned that incubation, with reagents potent in anti-IgG, could lead to false negative reactions with weakly IgG sensitized cells due to antibody surplus prozones of inhibition. This case illustrates that the rare instances of "Coombs negative immune hemolytic anemias" may be based on mechanisms such as those reported here and, that to be ideal, a broad spectrum anti-human serum should have balanced anti-immunoglobulin activities in relation to its incubation time.

IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI

“…3 However, wAIHA associated exclusively with IgA antibodies, reacting optimally at 37°C, remains rare. 1,[4][5][6][7][8] Some of the features of these reported cases, including disease severity, high binding potency of IgA for RBCs with very little free antibody detectable in the serum, no strong evidence of blood group specificity, and in some cases, refractoriness to first-line treatment (administration of high doses of glucocorticosteroids), seem to be characteristic. 1 IgA antibodies exist in several forms, monomeric IgA, dimeric IgA, and polymeric IgA, all of which interact to some extent with the human IgA Fc receptor (Fc␣RI/CD89).…”

Autoimmune Hemolytic Anemia Associated with IgA – Diagnostic and Therapeutic Aspects in a Case with Long-Term Follow-Up

“…Describing the first case of AIHA associated exclu sively with IgA, Stratton et al [19] requested adequate anti-IgA activity in broad-spectrum antiglobulin sera. Alternatively, in another report [12] the sensitivity for IgA in such a serum was enhanced by introducing a 5-min incubation period, but the authors warned that this procedure might bear the risk of false-negative IgG reactions due to antibody excess. These proce dures can be avoided, since monospecific anti-IgA reagents are commercially available.…”

“…The most common warm type antibodies involved are of the IgG class [3,4], IgA together with other immuno globulins is found in up to 19.3% on the surface of the erythrocytes, while IgA alone or in combination with complement is detected in less than 2% of all patients [5,6]. The identification of the autoantibodies causing the AIHA may give valuable information about the clinical course and the prognosis [7][8][9] and helps to clarify their pathogenetic role [10,11], In case of an AIHA associated with IgA alone the direct antiglobu lin test with a broad-spectrum antiserum routinely used for screening may turn out falsely negative, be cause the anti-IgA activity of such a serum is usually too weak or lacking completely [12,13].…”

Serological and Clinical Aspects of Autoimmune Hemolytic Anemias

“…IgG4 does not decrease the life span of RBCs, and large quantities of IgG2 are required to induce hemolysis [8][9][10]. Although IgA seems to cause severe hemolysis in isolated cases, the mechanism of IgA-mediated RBC destruction has yet to be fully clarified [11][12][13][14]. Moreover, some findings suggest that non-complement-activating IgM antibodies can also cause RBC destruction [15].…”

“…The possibility that alloantibodies might be detected in eluates but not in the serum of patients who recently received blood transfusion cannot invariably be excluded. [11][12][13][14]. In contrast, incomplete IgM antibodies usually remain undetectable in the presence of specific antiglobulin serum [15,31,39].…”