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Class I and Class II HLA antigens were tested in patients treated for thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (TTP/HUS) to determine whether there is a disease association. Based on the results of a pilot trial, retrospective HLA-typing of 18 patients with a diagnosis of TTP/HUS and prospective typing of 12 newly diagnosed patients with TTP/HUS were performed. Twenty-one patients were non-Hispanic Caucasians, 7 were African-Americans, and 2 were Hispanic-Caucasians. Of 30 patients tested, 28 were positive for DR52 (chi-squared = 5.14, P < 0.05), and only two were positive for DR53 compared to 57% of controls (chi-squared = 18.5, P < 0.0005). Diverse DR52 subtypes (DRB3*0101, DRB3*02, and DRB3*0301) were found by oligonucleotide testing in 15 patients, suggesting the association was not with DR52 but with absence of the DR53 antigen. The 2 patients with DR53 were not homozygous. This study suggests that the supertypic antigen, DR53, may govern susceptibility to TTP/HUS, since the relative risk of this disease among DR53 positives is reduced at 0.09 (95% confidence interval, 0.01-0.28). This finding indicates a possible immunogenetic component in the pathogenesis of TTP.

The 4-day response of C3H/HeJ mice to sheep erythrocytes was suppressed by a lipid-free teichoic acid with an average molecular weight of 2,900 when it was administered by the intraperitoneal route. Enhancement was not observed at that time, and neither suppression nor enhancement could be demonstrated by the intravenous route. Either suppression or enhancement of background plaques could be induced, depending upon the timing. Dosage influenced the degree of suppression from 8 to 100 micrograms, whereas suppression of background plaques required only 1 microgram of lipid-free teichoic acid. The kinetics of the sheep erythrocyte response was altered by treatment of the mice with lipid-free teichoic acid, delaying the peak until day 5 and producing enhancement at that time. Although lipid-free teichoic acid was shown to be toxic for mouse splenocytes (50% lethal dose, ca. 200 micrograms) in vitro, no effect at the levels employed was observed in vivo. The data presented indicate that modulatory activity is influenced by route, timing, dosage, and apparently the number of antibody-secreting cells.

Guinea pigs which were injected with either whole bacilli or purified soluble glycerol teichoic acid (GTA) usually exhibited a rise in hemolysin titer to GTA-coated erythrocytes. The only exceptions were those animals having high baseline titers of natural anti-GTA antibodies. Rats yielded better responses than guinea pigs and produced significantly higher responses to the soluble antigen than to the cellular GTA. Rats reared on a GTA-free diet were predominantly free of natural antibodies to GTA and furnished a more clear-cut model for assaying immune responses. Using this model, it was shown that adsorption of GTA to homologous erythrocytes before injection resulted in poor responses, suggesting that such spontaneous adsorption does not account for the good responses to soluble antigen. In GTA-deprived rats, positive skin tests were induced only with bacilli, whereas migration inhibitory factor was induced with both bacilli and soluble antigen. Hemolytic plaques in immunized rats were increased over controls with both kinds of immunogen, but the GTA-deprived rats responded better than conventional ones, and hemolytic plaque responses to bacilli were better than those to soluble antigen. This reversal of the serum hemolysin results may be due to delayed suppression by soluble GTA or to antibody cycling. The guinea pig data, combined with results from GTA-deprived rats, suggest that high antibody levels resulted in depressed antibody synthesis, perhaps because antibody cycling was initiated. No evidence was found to explain the superior responses to soluble antigen, but it did not seem related to formation of immune complexes or adsorption to erythrocyte membranes.

The frequencies of erythrocyte MNSs antigens and certain histocompatibility leukocyte antigen (HLA) specificities (HLA-A, HLA-B, and HLA-DR) were determined in white patients with meningitis or epiglottitis due to Haemophilus influenzae type b and in controls. The frequency of the erythrocyte MNSs genotype was significantly lower among patients with meningitis than among those with epiglottitis (P = 0.03); this observation confirms a trend observed previously. However, the frequencies of the HLA specificities did not differ significantly in the three groups studied; this result fails to confirm previous reports of disease associations with several HLA-A and HLA-B specificities. Although susceptibility to different clinical manifestations of haemophilus disease may be influenced by genetic factors, our studies indicate that the major loci conferring susceptibility are not in linkage disequilibrium with specificities in the major histocompatibility complex.