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Two well characterized Eighth International Workshop sera, 8w1090 and 8w112 , described to have anti-DR3 and anti-DR5 activity, respectively, were tested by standard and antiglobulin augmented (AHG) complement dependent cytotoxicity (CDC) assays with 21 target cells. We demonstrate that both sera, in fact, have only one antibody (most likely anti-MT2), but have different CYNAP patterns. These observations are discussed with regard to a more complete analysis of antisera that detect gene products of the HLA-DR region.

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.

• Several reports have found conflicting data regarding the association between lichen sclerosus et atrophicus (LSA) and HLA types. Association with HLA-A31 and -B40 has been noted, whereas another report found no correlation. We are the first to specifically examine HLA types in white patients in the United States. We have found a significant association between LSA and HLA-A29 and -B44 individually and an even stronger association with the combination of A29 and B44. A review of previous LSA-HLA studies, as well as several reports of HLA typing in familial LSA, is discussed, with consideration given to possible reasons for the discrepancies among the various studies. ( Arch Dermatol. 1990;126:1043-1045)

Genes associated with immunoglobulin (Ig) allotype determinants are important in regulation of immune responses to bacterial polysaccharides. Furthermore, loci associated with Ig allotypes have been reported to interact with those associated with the major histocompatibility complex and affect susceptibility to certain diseases. In the present study we determined the frequencies of certain Gm phenotypes in patients with Haemophilus meningitis or epiglottitis and in controls. HLA-A, -B and -DR specificities had previously been determined in the majority of these subjects. Although no Ig phenotype was associated with increased or decreased relative risk of disease, the frequencies of several combinations of HLA specificities and Ig phenotypes were significantly different from those of controls. Thus, for subjects with the Gm phenotype (1, 3, 17; 23; 5, 13, 21), the risk of Haemophilus meningitis or epiglottitis was lower in individuals with HLA-B5 than in those without this specificity (odds ratio less than 0.1, P less than 0.004). In contrast, for subjects with the closely related Gm phenotype differing only by the absence of Gm(23), (1, 3, 17; ; 5, 13, 21), the risk of disease was higher in those with HLA-DR3 than in individuals who lacked DR3 (odds ratio = 11.0, P = 0.02). Although the present data require confirmation in an independent sample, they suggest that complex interactions between genes at two independent loci controlling HLA and Ig allotypes, respectively, may affect susceptibility to Haemophilus disease.

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.

Animal or human blood protein is a costly but necessary additive to tissue culture. This supplemental protein is provided by the addition of pooled serum or heparinized plasma to standard tissue culture media. Many blood centers store CPDA-1 anticoagulated plasma, a form that does not provide optimal support of mixed lymphocyte culture (MLC). The optimal amount of CaCl2 (1 ml of 1 M CaCl2/100 g) added to citrate plasma and the use of glass vessels result in a completely clotted product that is comparable in MLC support to commercially available pooled human serum. Laboratories that have access to CPDA-1 plasma can replace the growing demand for serum with recalcified plasma without sacrificing quality.

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.

It has been shown previously that ingestion of glycerol teichoic acid (GTA) in the conventional laboratory diet (8 mg/kg) is the stimulus for natural background responses to GTA in rats. Since injected GTA suppresses responses to sheep red blood cells (SRBC), it was suspected that dietary GTA also might be acting suppressively. A comparison of rats fed the conventional diet with rats fed a GTA-free diet showed that ingested GTA markedly suppressed immune and background direct plaque-forming cell (PFC) responses to SRBC. It appeared that a direct causal relationship existed between the degree of suppression and the amount of GTA exposure. When GTA-deprived rats were force-fed varying doses of GTA or when conventional animals were injected (i.p.) with GTA, increasing the total GTA dose resulted in decreased direct PFC responses to SRBC. Suppression was also observed when GTA-deprived rats were force-fed GTA-containing Bacillus sp. ATCC 29726. The phenomenon of suppression by dietary GTA was not restricted to responses to SRBC, as similar results were obtained with chicken erythrocytes. When IgG PFC were measured, no difference between conventional and GTA-deprived groups was observed. Thus, an IgM-IgG shift does not seem to play a role in the mechanism of suppression by GTA.

We have used the antiglobulin augmented cytotoxicity assay and platelet absorption-elution techniques to investigate crossreactivity among certain antigens coded by the HLA-A locus. These serologic and absorption studies demonstrated two supertypic determinants, distinct from private determinants, associated with HLA-A locus gene products. One determinant was present on HLA-A2, Aw23, Aw24, and A28 bearing lymphocytes; the other was found on HLA-A28, Aw33, Aw34, and A26 bearing lymphocytes. The second determinant was not associated with HLA-A25. Both supertypic determinants are associated with HLA-A28.

Between January and March 1984, the first community outbreak of transient thyrotoxicosis in the United States was documented in a seven-county area of southeastern Nebraska; 36 of the total 49 patients resided in York County (2.4 cases per 1,000 population). The median age of patients was 36 years, range six to 82 years; 51 percent were women. By definition, all patients were symptomatic, visited a physician, and had a newly identified elevated serum concentration of thyroxine or triiodothyronine of unknown cause. None had a goiter or a painful thyroid gland. Low 131I uptake measurements were found in all nine patients studied. Six patients were hospitalized; none died. Investigation of all 12 household contacts of eight selected patients revealed five additional persons with thyrotoxicosis and four with asymptomatic hyperthyroxinemia. A case-control study revealed that illness was associated with a significantly higher frequency of a reported recent respiratory viral-like condition. In another case-control study, the HLA-DR3 antigen was present in more case subjects (39 percent) than control subjects (14 percent). In addition, a significantly higher proportion of patients than control subjects purchased beef from one of the three supermarkets in York Country. Concomitant with the outbreak, the supermarket implicated in the outbreak purchased an unusually large quantity of beef (7,000 pounds) from a nonregular supplier in Nebraska, which had reportedly instituted the practice of trimming gullets (a procedure that removes the muscles from bovine larynx for beef) about three months earlier. Thus, it is concluded that the Nebraska outbreak, like one in Minnesota that occurred 18 months later, probably resulted from patients having eaten ground beef that was contaminated with bovine thyroid gland. This form of thyrotoxicosis, perhaps misdiagnosed as painless thyroiditis in the past, probably represents a previously under-recognized public health problem.

HLAA1. HLAA1 was designated in 1967 as Da-11 by Dausset et al. (6) and in 1964 as LA-1 by Payne et al. (14). It is common in Caucasians, less frequent in blacks,and very rare in Orientals. It received its present designation at the Sixth International Histocompatibility Workshop and was well defined in the Eighth and Ninth Workshops with no evidence of split specificity (8,11). HLA Aw36 was originally demonstrated in African blacks (19) and closely associated with A1.