Historical Note: Past, Present and Future of the Antiglobulin Test

Abstract

This is a review of two invited talks on the antiglobulin reaction on the occasion of the 50th Anniversaries of the International Blood Group Reference Laboratory, now at Bristol, and the National Blood Service, London, and coincidentally the 51st anniversary of the antiglobulin test! The first talk (as specially requested) is a very personal reminiscence of the discovery, with Rob Race and Arthur Mourant, of the antiglobulin test in blood group serology. The second talk traces developments in antiglobulin testing in general immunology using, of course, isotype-specific antiglobulin reagents as and when they became available. Special emphasis was given to: (1) testing for poorly agglutinating bacterial antibodies; (2) special procedures for measuring reaginic (IgE) antibodies to various allergens; (3) the incorporation of an antiglobulin step or stage in many of the routine automated immunoassay procedures; (4) the special experimental procedures in the form of mixed antiglobulin reactions to reveal antibodies to the surface antigens on tissue cells, and, finally, (5) by chemically coupling antiglobulin to red blood cells, a distinctive integrated immunoassay system was developed, enabling reverse passive haemagglutination as an assay for immunoglobulins, rosetting reactions to reveal native IgG receptors on lymphocytes or antibody immunoglobulin reacting with CD marker antigens; this same reagent, namely red-cell-labelled antiglobulin, can be used to detect antibodies reacting with either bacteria or antigens adsorbed on the walls of wells of microtitre plates. The need for improved stabilization and preservation of the antiglobulin-linked red cells to prolong their ‘shelf-life’ is stressed.

The Direct Antiglobulin Test: Still a Place for the Tube Technique?

“…The history of the test has been reviewed recently by R.R.A. Coombs himself [1]. It has been reported that the gel test, a novel and promising method described by Lapierre et al [2], is as good or better than the conventional tube technique for demonstrating in vivo antibodies and/or complement coating red blood cells [3].…”

The spherocytic Haemolytic Anaemias

“…It was shortly before July 1945 that, according to Mourant (1983), Dr Coombs conceived the principle of the anti‐globulin reaction in a brilliant feat of intuition. Dr Coombs (1998) described a late night ride on an ill‐lit train from London to Cambridge during which he was pondering the nature of the incomplete antibodies attached to RBCs, with visions of Ehrlich's side‐chain theory running through his head. ‘In a flash I could see the globulin antibody on the red cells, and these cells should be agglutinated with an antibody to serum globulin, i.e.…”

The sensitivity, specificity, and clinical relevance of gel versus tube DATs in the clinical immunology laboratory

“…However, it was not until 1945, when Coombs showed that blood group antibodies could be demonstrated in serum or on sensitized RBCs, that the test was adopted by clinical laboratories. 1 The DAT is an essential test in the evaluation of autoimmune hemolytic anemia (AIHA). The DAT also has importance in the blood bank, where it is performed as part of the evaluation of hemolytic transfusion reactions.…”