Clinico-immunogenetic study on Egyptian multicase tuberculous families

Thirteen multicase Egyptian families (having more than one sib affected) with pulmonary tuberculosis have been studied. They include 26 parents (4 were tuberculous) and 53 sibs (30 tuberculous and 23 healthy). For all of them the following have been carried out: (a) Clinical, radiological, and bacteriological examination for diagnosis and evaluation of the disease severity; HLA-antigen determination using 9(A), 16(B) and 6(DR) antigens. The analysis of data revealed: (1) high incidence of tuberculosis among sibs in families having A2 B5 in their haplotypes compared to those having A2 X or B5 X--affected sibs with A2 B5 showed more severe manifestations than those having only one of the two antigens; (2) aggregation of HLA concordance among the sib pairs, both fully identical and haploidentical, while none of the sib pairs is non-identical; (3) Lod score studies showed linkage between the genetic control of susceptibility to pulmonary tuberculosis and HLA; (4) identity by descent study confirms the dominant pattern of transmission. The recommendation is that in a clinical setting of genetic counselling healthy individuals having either A2 or B5 antigens in their haplotypes should be vaccinated with BCG. Furthermore tuberculous patients having these HLA antigens should be managed aggressively, especially those having A2 B5 haplotypes in whom the disease is likely to run a severe course.