No abstract

A familial aggregate of seven cases of Hodgkin's disease (HD) has been investigated by HLA typing. Over 600 people in the immediate population (i.e. about half) have been HLA typed and haplotypes have been obtained for 95% of them. It was expected that the cases would share a particular HLA haplotype or at least that they would have one or two HLA antigens of the same series in common. However, this was not the case so no simple idea of association of HLA with HD cases was upheld. When antigen frequencies were examined in the whole population, it was found that HLA B18 increased progressively in incidence from 0.08 to 0.4 in successive groups of individuals each one more closely related to the HD cases. Similarly the community with the highest incidence of HD also had the highest incidence of B18. Thus B18, which in the world figures carries the highest relative risk, emerged as important in this study. Of four proposed interpretations of the data, we are most interested in the idea that the important HLA association is at a population level rather than at the level of the individual patient. A hypothesis, based on the concept of a "healthy carrier" for the HD agent, explains how such an association might operate. It is possible that B18-linked complement deficiency could be the basis for such a carrier state.

No abstract

In three adjacent Newfoundland communities comprising some 1500 people, 589 people have been HLA typed. Forty-six of the typed people gave a history of previous clinical tuberculosis which required treatment. Fifty-six percent of the TB patients carried HLA B8 compared with 20% of the remainder of the population. This is a highly significant difference (P less than 0.01). In each community the frequency of B8 as an epidemiological marker correlated with the incidence of tuberculosis. B8 is associated with TB in ths study with a relative risk of 5.2 which compares with combined relative risks in the literature for coeliac disease and Addison's disease of 9.5 and 6.4, respectively, and which is greater than the risks for all the other B8-related diseases. The factor B allele, Bf S, was found on all the B8 haplotypes, but the overall Bf gene frequencies in tuberculosis patients did not deviate from expected values.

Although HLA-B27 carries a high relative risk for development of ankylosing spondylitis (AS), most B27 positive individuals do not have spondylitis. One interpretation of this observation is that there may be 2 types of B27, 1 which carries the risk factor and 1 which does not. If this were the case, then with the help of markers closely linked to HLA-B, it might be possible to detect differences between the B27 haplotypes in AS patients and those in healthy probands. We studied 197 members of 18 families with known AS and 110 members of 19 families in which HLA-B27 was present without any known inflammatory spinal disease. HLA antigens A, B, and C and alleles of complement components C2, C4, and Factor B and glyoxalase-1 were determined in all cases. Detailed haplotypes were assigned and their associations with development of the disease were examined. We were unable to identify any distinct HLA-B27 haplotype associated with AS; 2 common haplotypes and several miscellaneous ones were found in both groups. Thinking that the development of AS might be influenced by the other, non-B27 haplotype, we analyzed this and found that there was no detectable influence. The data do not contradict the notion that B27 in whites is a single entity and is itself the susceptibility factor predisposing to the development of ankylosing spondylitis.

No abstract

Tmder, 0. Influence of antibodies and thermolabile serum factors on the bactericidal activity of human neutrophil granulocytes. Acta path.microbiol. scand. Sect. C , 84: 112-118, 1976.The influence of serum antibodies and thermolabile serum factors on the intracellular killing of Staphylococcus aureus by neutrophil granulocytes has been examined using a method which facilitates a precise in vitro evaluation of the phagocytic and bactericidal activities of human polymorphonuclear leucocytes. The bactericidal activity of the granulocytes was significantly less pronounced in the presence of serum absorbed with Staph. aureus or inactivated at 56" C for 30 minutes than in the presence of untreated serum. Specific antibodies seemed to stimulate the intracellular killing of bacteria more than thermolabile serum factors.

In a large kinship affected by myotonic dystrophy (MyD), 133 subjects, including 21 spouses, were examined independently by a neurologist and an ophthalmologist to determine the earliest identifying evidence of the disease. Assessment included tonometry, slit-lamp examination, facial measurements, and electromyography (EMG). Thirty-two subjects, all of whom had EMG characteristics of myotonia, were definitely affected. Low intraocular tensions were a more consistent finding than lens opacities; endocrine abnormalities were absent. Twenty-seven subjects had one to five features but lacked clinical or electrographic evidence of myotonia; they were designated as having a "partial syndrome." Signs most commonly found included weakness of the upper face, brachial hyporeflexia, low intraocular tensions, and the presence of sparse colored specks at the posterior poles of the lenses. All but 2 subjects (siblings) with the partial syndrome had a parent with either MyD or the partial syndrome. Linkage studies indicated that 7 subjects should not be carrying the gene, while others could be regarded as having a minor expression of MyD. In most persons with the partial syndrome, we could not predict whether typical MyD would develop later. Transmission of the disease may depend upon more than a single autosomal dominant gene, and nongenetic influences may also be important.