Specificity of Acquired Haemolytic Anaemia Autoantibodies and their Scrological Characteristics

Abstract

Summary In a study of 24 red cell eluates obtained from patients with acquired haemolytic anaemia of the ‘warm’ type, it was established that some eluates possessed autoantibody of only one specificity either for ‘normal’ (‘anti‐nl’) or ‘Rhnull’ (‘anti‐dl’) red cells, whereas others contained autoantibodies of both specificities. Combined autoantibodies were often better recognized by different testing procedures than by the same method. Thus the ability of these autoantibodies to strongly sensitize ‘normal’ red cells by the ficin test and ‘Rhnull’ cells by the antiglobulin test was frequently found, whereas the occurrence of strong ficin‐reactive ‘anti‐nl’ and strong ficin‐reactive ‘anti‐dl’ was rare. Additional studies using red cell eluates revealed that no direct correlation could be established between the presence of complement components and the intensity of the indirect antiglobulin test using anti‐IgG serum. On the other hand, the simultaneous presence of ‘anti‐nl’ and ‘anti‐dl’ autoantibodies was often associated with the presence of complement components in the red cell eluates. Fixation of complements by Rh isoantibodies of multiple specificity has been reported, and thus the presence of complement components in association with ‘anti‐nl’ and ‘anti‐dl’ may be analogous to complement fixation by multiple Rh isoantibodies. The formation of ‘anti‐nl’ with ‘anti‐dl’ which tends to result in complement components being fixed by the antibody may be considered as a natural progression of antibody synthesis associated with an advanced state of autoimmunization.

Reactivity of autoantibodies of autoimmune hemolytic anemia with recombinant rhesus blood group antigens or anion transporter band3

“…The specificities of Rh-associated autoantibodies have been de-duced mainly from observations of selectively weak or negative reactions with Rh null RBCs. A part of the autoantibodies reacted with RBCs expressing a distinct known Rh antigen such as Rhe, E, c, or D, but careful serological analysis discriminated the antibodies from allo-anti Rh antibodies [4,5]. Issit et al [6] have shown that a high frequency antigen, Wright b (Wr b ), is a major autoantigen, which was recently found to be constructed from an association with RBC anion transporter glycoprotein (band3) and glycophorin A (GPA) [7].…”

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

“…4 and 5). Moreover, a large body of serological data had strongly suggested that one or more proteins ofthe Rh complex serve as target antigens in many cases of AHA (6)(7)(8)(9)(10)13) and in the great majority of a-MD-associated autoantibodies (34).…”

“…Cautious interpretation of these observations was warranted, however, by the knowledge that Rhnull RBCs have membrane anomalies other than deficiency of Rh antigens ( 11 ) and by the fact that careful serological analysis has suggested subtle differences between, e.g., auto-anti-e and allo-anti-e (12). Moreover, in many other AHA patients, the reactivity of their autoantibodies with Rhnu11 RBCs and RBCs of "normal" phenotype was equally strong, suggesting that in these patients the autoantibodies recognized RBC determinants distinct from known components ofthe Rh complex (6)(7)(8)(9)(10). Furthermore, through the use of human RBCs selectively deficient in other blood group antigens, evidence has accumulated in selected AHA patients for autoantibody specificity against serologically defined, non-Rh RBC antigens such as Wrb ( 13), Ena ( 14), LW ( 15), U ( 16), or antigens of the Kell blood group ( 17 ).…”

“…These autoantibodies characteristically react with essentially all human RBCs and with the RBCs of higher (old world) primates but not with RBCs of other species (2). In a significant proportion ofAHA patients, specificity oftheir autoantibodies for one or more determinants ofthe rhesus (Rh) blood group had been deduced from serological observations including selectively weak or negative reactions with Rhnull RBCs, which lack any known expression of the Rh complex (6-10); or selective or preferential reactivity with RBCs expressing known Rh antigens such as "e," "E," or "c," also present on the patient's own RBCs (2,6,8,9). The latter antibodies were usually found in combination with less well-defined autoantibodies.…”

A Bromelin Dependant ‘Pan-Agglutinin’

“…Their specificity may parallel auto antibody specificity in auto-immune haemolytic anaemia [18]. These agglu tinins are usually identified only when using papainised, ficinised or trypsintreated red cells [3,10,15].…”