Immunogenetic susceptibility for post-schistosomal hepatic fibrosis.

In 19 children with hepatic fibrosis as the result of continued schistosomiasis mansoni and 20 children without hepatic fibrosis, the following studies were carried out: HLA antigen typing for 30 antigens, immune response of T lymphocytes to schistosome antigen by measuring DNA synthesis evidenced by 3H-thymidine uptake, and measurement of total OKT3+, OKT4+, and OKT8+ cells using monoclonal antibodies. Patients with hepatic fibrosis were mostly high responders in contrast with those without fibrosis. High immune response and susceptibility to post-schistosomal hepatic fibrosis were associated with a high frequency of A2 and B12 antigens and a lack of DR2 antigens, while low response was associated with the presence of the DR2 antigen. The T4+:T8+ ratio showed increased suppressor proportions in patients with low immune response and/or with no hepatic fibrosis. We suggest an immunogenetic susceptibility for post-schistosomal hepatic fibrosis, probably controlled by HLA-linked genes via the suppressor T cells.

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.

Evidence of inherited susceptibility of increased streptococcal adherence to pharyngeal cells of children with rheumatic fever.

The study included the members of 15 families, each having more than one sibling affected by rheumatic fever (RF). All the rheumatic individuals showed the sequelae of rheumatic carditis, but on clinical and laboratory evidence, the disease was inactive. Thirty normal unrelated individuals, having no rheumatic first-degree relatives, were studied as controls. The following investigations were carried out for all members: (1) history and clinical examination, (2) routine investigations of diagnosis, (3) HLA typing using 9-A, 15-B, 6-DR antigens, (4) adherence of group A streptococci to pharyngeal cells, an in vitro adherence assay. There were two types of strains; five RF-associated strains and two RF-unassociated strains. Statistical and genetic analysis revealed: (1) no significant difference between adherence of RF-associated and unassociated strains amongst controls; (2) significant increased avidity for adherence of RF-associated strains amongst rheumatic siblings compared to normal siblings and controls. There was no significant difference between the three groups using RF-unassociated strains; (3) HLA-haplotype concordance and 'N' measure showed that the avidity for adherence is probably inherited; (4) lod scores for linkage suggest a dominant susceptibility gene(s) closely linked to HLA and segregating in multiplex families.

HLA-antigens in Guillain-Barré syndrome.

A microlymphocytotoxicity test determined serologically the frequency of HLA antigens in 32 patients with Guillain-Barré syndrome and in 234 healthy control subjects. The results demonstrated significantly increased frequencies of A3 and B8. The relative risk was estimated to be 9.6 and 4.6 for the A3 and B8 antigens, respectively. Study of the gametic association revealed weak positive linkage disequilibrium and biological association. The results are discussed, and it is concluded that the aberrant genetic make-up of the patients makes them more susceptible to develop the syndrome after exposure to the environmental factor(s).

HLA antigens and acute rheumatic fever: evidence for a recessive susceptibility gene linked to HLA.

From 60 probands with acute rheumatic fever (ARF), 19 multiplex families segregating for ARF were ascertained. The parents and rheumatic and normal sibs of the probands in these 19 families were also studied. HLA typing using the microlymphocytotoxic assay was then performed on the 60 unrelated probands, the multiplex families, and 234 unrelated controls using 23 antigens from the HLA-A and -B loci. The controls lacked a past history of ARF and were from the same geographic locality. Calculations of relative risk demonstrate an increase of HLA-B5 antigen in the 60 patients, but the result might not be significant from the point of view of multiple comparisons. Nevertheless, affected sib pairs from the multiplex families show 93% concordance for both or one HLA haplotype. A formal linkage analysis demonstrates that a recessive etiology is most likely (lod score of 3.3) with approximately 68% of cases being due to a gene closely linked to HLA and in linkage disequilibrium with HLA-B5. The remaining 32% of cases are due to other familial factors such as polygenic inheritance or common environmental factors. The results confirm a strong genetic predisposition to ARF and its heterogeneous nature in families.