Evidence of HLA-linked susceptibility gene(s) in respiratory distress syndrome.

In a prospective study 101 newborns were enrolled into four groups: Group I included 38 unrelated newborns suffering from RDS and four sets of twin sibs (seven of whom had RDS; Group II included prematures free from RDS and any other disease; Group III included 21 newborns) delivered by C.S. and free from RDS and any other disease; Group IV included 20 infants of diabetic mothers free from RDS. HLA antigens were typed for all the newborns. The analysis of results could be summarized as follows. (1) Strong association between A3 antigen (RR = 19.4, WY2 = 59.8, S = 0.599) and B14 antigen (RR = 14.1, WY2 = 50.7, S = 0.489) and RDS. (2) HLA haplotypes were identical in twins sibs suffering from RDS and nonidentical in twins when one sib had RDS and the other is free. (3) The frequencies of A3 and B14 among the other three groups were insignificantly different from the general population and highly significantly low compared to RDS group. In conclusion, the development of RDS depends probably on the presence of susceptibility gene(s) in linkage disequilibrium with A3 and B14 antigens. Environmental factors, magnified by prematurity, in such susceptible newborns affect the production of surfactant leading to the development of RDS.