HL-A histocompatibility antigens and their relation to disease.

Table 14 summarizes the data presented in this review. The table lists the various diseases, along with whatever HL-A-antigen associations may be present, and the ranking that is based on the accumulated confidence of the associations; also, it lists the individual antigens and those disease states in which the incidence of the various antigens is increased ro decreased. The Table should expand rapidly in future years. There are a number of problems involved in this area of research: (1) There is a scarcity and lack of stability of good reagents, as well as the general difficulty of HL-A serology. (2) Many studies are retrospective on cells that may be abnormal. We have mentioned the changing sensitivity of lymphocytes to HL-A antibodies in disease. Increased sensitivity of weak antibodies present in the HL-A antisera may create the false impression of increased frequencies. (3) What control population one selects is also of the utmost importance. One method of internal control is to include in the controls related and unrelated individuals, all tests being run at the same time, employing the same reagents, and being run by the same technician. (4) In some disease states, notably Hodgkin's disease and SLE, autoantibodies present may interfere with the HL-A antisera reactions. All of this is compounded by the fact that the lymphocyte is constantly and rapidly shedding and replacing the HL-A antigens; the rate of turnover may change in patients, thus introducing an additional problem. Finally, there is a need for a standardization of statistical tools and for the reporting of both positive and negative results [133]. The concern for a significant quantity of test data and the problems of evaluating statistical data bring out many views. Boswell, in The Life of Samuel Johnson, noted: "I recollect nothing passed this day except Johnson's quickness, who, when Dr. Beattie observed, as something remarkable which happened to him, that he had chanced to see both No. 1 and No. 1000 of the hackney-coaches. The first and the last, 'Why Sir' (said Johnson) 'there is an equal chance for one's seeing those two numbers as any other two.'" A partial solution to these problems may be offered by the evaluation of the LD antigens [49, 63, 64]. In any event, HL-A typing offers an unique opportunity for the grouping of related diseases, as similar clinical findings with related distributions of HL-A antigens may indicate disease relationships not previously considered [27].