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.

1.
Coombs RRA, Coombs AM, Ingram DG: The Serology of Conglutination and Its Relation to Disease. Oxford, Blackwell, 1961.
2.
Coombs RRA, Race RR: Further observations on the ‘incomplete’ or ‘blocking’ Rh antibody. Nature 1945;156:233.
3.
Coombs RRA, Mourant AE, Race RR: Detection of weak and ‘incomplete’ Rh agglutinins: A new test. Lancet 1945;ii:15–16.
4.
Coombs RRA, Mourant AE, Race RR: A new test for the detection of weak and ‘incomplete’ Rh agglutinins. Br J Exp Pathol 1945;26:255–266.
5.
Moreschi C: Neue Tatsachen über die Blutkörperchen-Agglutination. Zentralbl Bakteriol Parasitenkd Infektkr 1 Originale 1908;46:49–51.
6.
Coombs RRA, Mourant AE, Race RR: In-vivo isosensitisation of red cells in babies with haemolytic disease. Lancet 1946;i:264–266.
7.
Moreschi C: Beschleunigung und Verstärkung der Bakterienagglutination durch Antieiweisssera. Zentralbl Bakteriol Parsitenkd Infektkr Originale 1908;46:456–460.
8.
Coombs RRA, Moreschi e alcuni recenti sviluppi nello studio della agglutinazioni. Informatore Med 1954;9:126–129.
9.
Friedemann U: Weitere Untersuchungen über den Mechanismus der Anaphylaxie. Z Immunitätsforsch Exp Ther 1 Originale 1909;2:591–641.
10.
Boorman KE, Dodd BE, Loutit JF: Haemolytic icterus (acholuric jaundice). Congenital and acquired. Lancet 1946;i:812–814.
11.
Van Loghem JJ, Kresner M, Coombs RRA, Roberts G Fulton: Observations on a prozone phenomenon encountered in using the antiglobulin sensitisation test. Lancet 1950;ii:729–732.
12.
Coombs RRA, Gorius J, Bessis M: Diagnostic de l’ictère hémolytique des muletons par le test l’antiglobuline. CR Soc Biol Paris 1950;144:688–691.
13.
Coombs RRA, Crowhurst RC, Day FT, Heard DH, Hinde IT, Hoogstraten J, Parry HB: Haemolytic disease of newborn foals due to iso-immunisation of pregnancy. J Hyg 1948;46:403–418.
14.
Buxton JC, Brooksbank NH, Coombs RRA: Haemolytic disease of newborn pigs caused by maternal iso-immunization. Br J Vet Med 1955;ii:463–473.
15.
Morgan WTJ, Schütze H: Non-agglutinating antibody in human anti-sera to Shigella shiga and Salmonella typhi. Br J Exp Pathol 1946;27:286–293.
16.
Coombs RRA, Stoker MGP: Detection of Q fever antibodies by the antiglobulin sensitisation test. Lancet 1951;ii:15–17.
17.
Wilson MM, Merrifield EVO: Antiglobulin (Coombs) test in brucellosis. Lancet 1951;ii:913–914.
18.
Kerr WR, Payne DJH, Robertson L, Coombs RRA: Immunoglobulin class of Brucella antibodies in human sera. Immunology 1967;13:223–225.
19.
Ceppellini R, Landy M: Suppression of blood group agglutinability of human erythrocytes by certain bacterial polysaccharides. J Exp Med 1963;117:321–338.
20.
Coombs RRA, Edebo L, Feinstein A, Gurner BW: The class of antibodies sensitizing bacteria measured by mixed reverse passive antiglobulin haemagglutination (MRPAH). Immunology 1978;34:1037–1044.
21.
Coombs RRA, Fiset ML: Detection of complete and incomplete antibodies to egg albumin by means of a sheep red cell-egg albumin antigen unit. Br J Exp Pathol 1954;35:472:477.
22.
Steele ASV, Coombs RRA: The red cell linked antigen test for incomplete antibodies to soluble proteins. Int Arch Allergy Appl Immunol 1964;25:11–25.
23.
Coombs RRA, Jonas WE, Lachmann PJ, Feinstein A: Detection of IgA antibodies by the red cell linked antigen-antiglobulin reaction: Antibodies in the sera of infants to milk proteins. Int Arch Allergy Appl Immunol 1965;27:321–337.
24.
Coombs RRA, Hunter A, Jonas WE, Bennich H, Johansson SGO, Panzani R: Detection of IgE (IgND) specific antibody (probably reagin) to castor-bean allergen by the red-cell-linked antigen-antiglobulin reaction. Lancet 1968;i:1115–1118.
25.
Scott ML, Thornley J, Coombs RRA: Comparison of red cell linked anti-IgE and 125I-labelled anti-IgE in a solid phase system for the measurement of IgE specific for castor bean allergen. Int Arch Allergy Appl Immunol 1981;64:230–235.
26.
Weller TH, Coons AH: Fluorescent antibody studies with agents of varicella and herpes zoster propagated in vitro. Proc Soc Exp Biol Med 1954;86:789–794.
27.
Coombs RRA, Bedford D, Rouillard LM: A and B blood-group antigens on human epidermal cells demonstrated by mixed agglutination. Lancet 1956;i:461–463.
28.
Chalmers DG, Coombs RRA, Gurner BW, Dausset J: The mixed antiglobulin reaction in the detection of human iso-antibodies against leucocytes, platelets and HeLa cells. Br J Haematol 1959;5:225–231.
29.
Garrett JV, Giles H McC, Coombs RRA, Gurner BW: Neonatal purpura with platelet iso-antibody in maternal serum. Lancet 1960;i:521.
30.
Coombs RRA, Franks D: Immunological reactions involving two cell types. Prog Allergy. Basel, Karger, 1969, vol 13, pp 174–272.
31.
Coombs RRA, Scott ML, Cranage MP: Assays using red cell-labelled antibodies. J Immunol Methods 1987;101:1–14.
32.
Scott ML, Merrett TG, Ishizaka K, Thornley MJ, Coombs RRA: Comparison of reverse passive antiglobulin haemagglutination with double antibody radio-immunoassay for estimation of total human serum IgE. Clin Exp Immunol 1982;48:417–422.
33.
Coombs RRA, Wilson AB: Rosette-forming reactions; in Lachmann PJ, Peters DK (eds): Clinical Aspects of Immunology, ed 4. Blackwell Scient Publ. Oxford 1982, vol 1, pp 343–397.
34.
Eggert FM, Edebo LB, Gurner BW, Coombs RRA: A simplified procedure for measuring the class of anti-bacterial antibodies by mixed reverse passive antiglobulin haemagglutination (MRPAH). J Immunol Methods 1979;26:125–140.
35.
Edebo L, Nilsson BO, Lindberg AA, Svenungsson B, Coombs RRA: Class of serum antibodies towards Salmonella enteritids in gastro-enteritis, as measured by mixed reverse passive antiglobulin haemagglutination (MRPAH). Acta Pathol Microbiol Scand B 1981;89:341–346.
36.
Kieffer M, Frazier PJ, Daniels NWR, Ciclitira PJ, Coombs RRA: Serum antibodies (measured by MRSPAH) to alcohol soluble gliadins in adult coeliac patients. J Immunol Methods 1981;42:129–136.
37.
Coombs RRA, Gurner BW, Oldham G, Barnes MJ, Kieffer M: Antibodies to type II collagen measured by mixed reverse (solid phase) passive antiglobulin haemadsorption. Int Arch Allergy Appl Immunol 1982;67:377–379.
38.
Cranage MP, Gurner BW, Coombs RRA: Glutaraldehyde stabilization of antibody-linked erythrocytes for use in reverse passive and related haemagglutination assays. J Immunol Methods 1983;64:7–16.
39.
Pegg DE, Diaper MP, Scholey SEG, Coombs RRA: Cryopreservation of antibody-coupled red cells for use in immunoassays. J Immunol Methods 1982;54:331–341.
40.
Pegg DE, Diaper MP, Scholey SEG, Coombs RRA: Droplet freezing of sheep, ox and human origin. Cryobiology 1982;19:573–584.
1998
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