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.

Inherited immunoregulatory dysfunction in extrinsic bronchial asthma.

We studied 119 members of 22 asthmatic multiplex families. Included were: 44 parents (seven were asthmatics), 48 asthmatics (23 were undergoing an attack at the time of sampling), and 27 normal siblings. The following investigations were carried out on all subjects: 1) detection of total T lymphocytes, helper cells, and suppressor cells, using monoclonal antibodies (OKT3, OKT4, and OKT8), 2) study of nonspecific T-lymphocyte blast transformation induced by PHA, and 3) HLA-A, B, and DR antigen determination using the microcytotoxicity technique. The results were compared with normal ranges and data for a normal group and statistically and genetically analyzed. They indicate that: 1) the number of T cells was low in asymptomatic asthmatics and normal in asthmatics in attack; 2) there were fewer helper and normal suppressor cells (that is, a low H:S ratio) in asymptomatic asthmatics, and a normal amount of helper and suppressor cells (a normal H:S ratio) in those experiencing an attack; 3) there was a percentage of lymphocyte transformation in both groups of asthmatics; 4) whereas the T-helper cells increased, there was no change in the number of suppressor cells during an attack, which points to deficient function of suppressor cells; 5) the disorder is inherited and the gene controlling this dysfunction is HLA-linked and probably dominant.