Current aspects of neurocysticercosis. Clinical and pathological report on 3 cases

The genetics of the serological defined SD antigens of the HLA system, which are governed by three closely linked loci (HLA-A, HLA-B and HLA-C) situated on the chromosome C6, are described. Regarding patermity testing, only the antigens coded by the loci HLA-A and HLA-B are used routinely up to now. Because of the strong linkage disequilibrium between these two loci, they cannot be considered as independent. The influence of the linkage disequilibrium on the calculation of the chance of paternity exclusion and of the plausibility of paternity is discussed and demonstrated in several examples.     

Histocompatibility antigens in multiple sclerosis in children

A phenotyping was done in respect of HLA system in 14 children with documented multiple sclerosis (MS), 20 children with potential MS, and 42 their near relations. HLA-B12 antigen was recordable with high frequency (RR = 6.29; P < 0.025) while HLA-B18 with low one (P < 0.01) as compared to normal subjects both among patients in the general group and in those with proved MS. The latter showed a tendency toward increase in frequency HLA-B7. Children with significant MS where there was an association in the phenotype of HLA-B12 or HLA-B7 with HLA-A3 ran predominantly an aggravating course while their association with HLA-A2 resulted in a more benign course. The results obtained in respect of HLA antigens in MS in children differ from those of other authors on MS in adults.     

A new HLA antigen apparently not controlled by the known HLA loci

The human allogeneic serum RM3 recognizes a lymphocyte structure inherited with the HLA chromosome. Population studies show several positive associations with antigens of the HLA-A and HLA-B series. Negative association have been found with antigens of the HLA-C series. Moreover the distribution of the RM3 factor is in Hardy-Weinberg equilibrium with that of the HLA-C alleles. However, serological investigations (namely the 'lysostrip' technique) bring evidence that RM3 serum does not appear to contain antibodies directed against any of the antigens of the HLA-A, B and C series. The study of a segregant family, showing a crossing over between the HLA-A and HLA-B loci, shows that the RM3 factor segregates on the side of the HLA-A locus. In conclusion, within the limits of the serological approach used, the present study presents evidence of a new serologically defined HLA locus, different from those so far described.     

Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program

BACKGROUND: The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established. METHODS: We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder. RESULTS: Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Matching [corrected] of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis. CONCLUSIONS: Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.     

Human leukocyte antigen class I expression. Marker of poor prognosis in uveal melanoma

PURPOSE: Because the expression of human leukocyte antigen (HLA) antigens is important for immunologic recognition of tumor cells, we determined expression of locus-specific HLA class I antigens in uveal melanoma and tested whether the level of HLA expression was related to prognosis or associated with known prognostic parameters. METHODS: Expression of HLA-A and -B antigens was determined on 30 formalin-fixed and paraffin-embedded sections of uveal melanoma by immunohistochemistry with locus-specific monoclonal antibodies and scored semiquantitatively. RESULTS: The level of expression of HLA-A and -B varied between uveal melanomas. Expression levels of HLA-A and -B were significantly correlated (P = 0.02). High HLA-B expression was significantly correlated with the presence of epithelioid cells (P = 0.04) in the tumor. Expression levels of HLA-A as well as of HLA-B, cell type, mitotic rate, Mib-1 score, and largest tumor diameter were significant predictive factors for survival. High expression of HLA-A and -B was associated with a decreased survival. Multiple Cox regression analysis with stepwise selection of covariates showed that the contribution of HLA-A expression to survival (P = 0.0003) exceeded that of tumor diameter (P = 0.02) and Mib-1 score (P = 0.04). CONCLUSIONS: Lack of expression of HLA-A as well as of HLA-B antigens on uveal melanoma is correlated with a better patient survival. Our data suggest that shedding of uveal melanoma micrometastases with a low expression of HLA class I into the systemic circulation may facilitate their removal and prevent the development of metastases. These findings support a protective role for natural killer cells in the development of metastatic disease in uveal melanoma.     

Human leucocytic antigens (HLA) in breast cancer

HLA frequencies of fifty (50) female breast cancer patients were compared with 200 age matched female controls. A total of 20 HLA-A locus, 35 HLA-B locus and 8 HLA-C locus antigens were studied. The HLA-A2, A11, Aw19 and A30; HLA-B8, B14 and HLA Cw6 were found significantly higher than the controls. The HLA-A11, HLA-Aw19 and HLA-B8 were found protective whereas, HLA-A2, HLA-B14 and HLA-Cw6 were a risk for breast cancer. The prective antigens' probable involvement through immunogenic mechanism in breast cancer is emphasized in this article.     

Gender differences in general practice consultations: methodological challenges in epidemiological research

The present study is an analysis of the frequencies of HFE mutations in patients with different forms of iron overload compared with the frequencies found in healthy subjects from the same region. The frequencies of HLA-A and -B antigens and HLA haplotypes were also analyzed in the same subjects. The study population included: 71 healthy individuals; 39 genetically and clinically well-characterized patients with genetic hemochromatosis (HH); and 25 patients with non-classical forms of iron overload (NCH), excluding secondary hemochromatosis. All subjects were HLA-typed and HFE-genotyped by the oligonucleotide ligation assay (OLA). The gene frequencies found for the C282Y and H63D mutations of HFE were respectively: 0.03 and 0.23 in healthy individuals, 0.86 and 0.04 in HH patients, and 0.08 and 0.48 in NCH patients. An expected significant association between HH and HLA-A3 was observed, which was found to be in linkage disequilibrium with the C282Y mutation. A new association was seen, however, between HLA-A29 and NCH, in linkage disequilibrium with the H63D mutation. Again as expected, the HLA-B antigen B7 was associated with HH in linkage disequilibrium with HLA-A3. In addition, the HLA-B antigen B44 was found to be associated with NCH but not in linkage disequilibrium with either A29 or the H63D mutation. In conclusion, a new association of the HFE H63D mutation with forms of hemochromatosis other than HH and a new association between the HLA phenotype A29 and the HFE H63D mutation were found in the same patients. These findings reinforce evidence for the involvement of the major histocompatibility class I in iron metabolism, supporting the notion of a physiological role for the immunological system in the regulation of iron load.     

Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis

Diffuse panbronchiolitis (DPB) in East Asia is a distinctive chronic obstructive pulmonary disease of unknown etiology. We hypothesize that the disease susceptibility is due to genetic predisposition unique to Asians. Association between human leukocyte antigen (HLA)-Bw54 and the disease was previously reported. In the present study, using newly developed polymerase chain reaction (PCR)- based methods, we directly analyzed HLA class I and II alleles in 76 Japanese patients. HLA-A, -B, and -C antigens were screened by the conventional typing method, and then B22-group alleles including HLA-B54 were genotyped by single-strand conformation polymorphism analysis. Alleles of HLA-DRB1 gene were fully determined by the microtiter plate hybridization method. Thirty-seven percent of the patients possessed HLA-B*5401 allele conserved predominantly in East Asians, as compared with 15% of 110 healthy volunteers (chi2 = 12.4, p = 0.0004). In addition, 4% of the patients possessed B*5504 also unique to Asians but a rare allele which was not found in normal control subjects in this study. Typing of HLA-DRB1 class II gene did not demonstrate strong positive association with the disease. A33, B44, and DRB1*1302 showed negative association with the disease. We conclude that distinctive molecular structure of HLA-B alleles or a closely linked gene in the HLA region contributes to genetic predisposition in diffuse panbronchiolitis. This may partly explain why this disorder is found primarily in Asians.     

Association of HLA-A9 and HLA-B5 with Buerger's disease

Eighteen patients who satisfied stringent criteria for the diagnosis of Buerger's disease, healthy controls, and patients with atherosclerosis were tested for various HLA antigens. The incidence of HLA-A9 and HLA-B5 was significantly greater among those with Buerger's disease. This finding supports the concept that Buerger's disease is a distinct clinicopathological condition.     

Linkage relationships of the loci of the major histocompatibility complex in families with a recombination in the HLA region

A number of families with an established recombination in the major histocompatibility complex has been investigated for markers known to be coded by genes of this linkage group. The results provide further data on the relative position of the loci for HLA-A, HLA-B, HLA-C, HLA-D, Bf, Chido, Rodgers and PGM3 on chromosome 6. A positive lodscore for linkage between HLA and blood group P was found; lodscores between HLA and nineteen other markers were negative.     

The primary physician and the family with a handicapped or chronically ill child

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS) is a benign acquired isolated chorioretinal disorder. Symptoms include photopsia, visual blur and scotomas. Ocular examination reveals multiple white dots at the level of the deep retina. A parainfectious disorder was suggested but the exact mechanism of MEWDS is still unknown. Postulating that MEWDS might be an antigen driven inflammatory reaction, we analyzed HLA subtypes in patients with MEWDS. PATIENTS AND METHODS: Sixteen patients were diagnosed with MEWDS in Lausanne from 1985 to 1994. Blood was withdrawn in 9/16 patients. HLA-A, -B and -DR were sought. RESULTS: HLA-B51 was detected in 4/9 patients (44.4%). Other HLA subtypes were detected sporadically. CONCLUSIONS: The frequency of HLA-B51 haplotype was found to be 3.7 times more elevated than in a normal control caucasian group. This suggests the possibility that MEWDS might be a genetically determined disorder as it is the case for other ocular diseases like Birdshot chorioretinopathy (HLA-A29), Harada's disease (HLA-DRMT3), acute anterior uveitis (HLA-B27) or Beh?et's disease (HLA-B51). We have no explanation for the presence of HLA-B51 in both Beh?et's disease and MEWDS. The association of HLA-B51 and MEWDS needs confirmation by further testing.     

Synthesis and antiviral activity of 7-O-(omega-substituted)-alkyl-3-O-methylquercetin derivatives

In a recent study, we observed a discrepancy rate of 8.5% between the results of molecular and serological HLA class I typing in Caucasian kidney donors and recipients. In the present study we addressed the question how often black individuals are mistyped using the serological technique. 421 Blacks whose HLA typing results were reported to the Collaborative Transplant Study (CTS) were typed retrospectively for HLA-A and -B using a PCR-SSP method. 78 of the 421 individuals (18.5%) showed a discrepancy for HLA-A and 107 individuals (25.4%) for HLA-B. 36.3% of all individuals tested showed either an HLA-A or an HLA-B discrepancy. 13.1% of the discrepancies at the HLA-A locus were due to antigen misassignments and 4.8% were due to missed antigens. HLA-B discrepancies were caused in 15.7% by antigen misassignments and in 10.5% by missed antigens. These results demonstrate an impressive advantage of the PCR-SSP method for HLA-A and HLA-B locus typing over serological typing in black individuals. The high typing discrepancy rate observed in Blacks provides a strong argument for replacing serological typing by the DNA method. It is likely that this will improve the HLA matching correlation in clinical transplantation in Blacks.     

The chromosomal order of genes controlling the major histocompatibility complex, properdin factor B, and deficiency of the second component of complement

The relationship of the genes coding for HLA to those coding for properdin Factor B allotypes and for deficiency of the second component of complement (C2) was studied in families of patients with connective tissue disorders. Patients were selected because they were heterozygous or homozygous for C2 deficiency. 12 families with 15 matings informative for C2 deficiency were found. Of 57 informative meioses, two crossovers were noted between the C2 deficiency gene and the HLA-B gene, with a recombinant fraction of 0.035. A lod score of 13 was calculated for linkage between C2 deficiency and HLA-B at a maximum likelihood value of the recombinant fraction of 0.04. 18 families with 21 informative matings for both properdin Factor B allotype and HLA-B were found. Of 72 informative meioses, three recombinants were found, giving a recombinant fraction of 0.042. A lod score of 16 between HLA-B and Factor B allotypes was calculated at a maximum likelihood value of the recombinant fraction of 0.04. A crossover was shown to have occurred between genes for Factor B and HLA-D, in which HLA-D segregared with HLA-A and B. These studies suggest that the genes for Factor B and C2 deficiency are located outside those for HLA, that the order of genese is HLA-A, -B, -D, Factor B allotype, C2 deficiency, that the genes coding for C2 deficiency and Factor B allotypes are approximately 3--5 centimorgans from the HLA-A and HLA-B loci, and that the apparent lack of recombinants between the Factor B gene and C2 deficiency gene suggests that these two genes lie in close proximity to one another.     

Renal cyst rupture following blunt abdominal trauma: case report

HLA typing was performed on 18 patients suffering from sarcoidosis and 30 patients suffering from diffuse interstitial pulmonary fibrosis. One hundred normal healthy people ethnically matched served as the controls. On statistical analysis, the corrected 'p' value of all the HLA antigens for both the patient groups was non significant. The results therefore suggest that there is no particular HLA antigen associated with sarcoidosis and diffuse interstitial pulmonary fibrosis.     

DNA typing for HLA-A and HLA-B identifies disparities between patients and unrelated donors matched by HLA-A and HLA-B serology and HLA-DRB1

High incidences of graft failure and graft-versus-host disease in the recipients of bone marrow transplantations (BMT) from unrelated donors (URD) may reflect the existence of allelic disparities between the patient and the URD despite apparent HLA identity at HLA-A, HLA-B, and HLA-DRB1 loci. To identify the extent and pattern of allelic disparities at HLA-A and HLA-B loci, 128 patients and 484 potential URD were evaluated by DNA typing. DNA typing for HLA-A, HLA-B, and HLA-DRB1 was performed at Memorial Sloan Kettering Cancer Center. HLA-A and HLA-B serotyping on URD was provided by the registries. By original typing (serology for HLA-A and HLA-B; DNA typing for DRB1) 187, 164, and 133 URD were 6/6, 5/6, and 4/6 matches, respectively. Following DNA typing, however, only 52.9% of the originally 6/6 matched URD remained 6/6, while 38.5%, 7.5%, and 1.1% were found to be 5/6, 4/6, and 3/6 matches. The level of disparity was higher in the originally 5/6 (P <.01) and 4/6 (P <.01) matched URD. A higher level of disparity was seen for HLA-B as compared to HLA-A. In addition, a serotype related variation was also noticed. For example, 24.1% of HLA-A2 and 60.1% of HLA-B35 seromatched URD were genotypically disparate, but no disparities were seen for HLA-A1 and HLA-B8. A higher percentage of HLA-A (67. 4%) compared with HLA-B (35.4%) serologic homozygous URD remained genotypically homozygous (P =.01). The level of allelic disparity was lower (P <.01 for 6/6; P =.02 for 5/6) if the patient had one of the 15 most common haplotypes (A1B8DR3, A2B7DR15, A3B7DR15, etc) in comparison to the rest of the group. Outcome studies will answer the question whether these disparities are associated with a higher rate of immunological complications seen with URD-BMT.     

Schizophrenic psychoses and HLA antigens. Personal data and review of the literature

Genetic factors play probably an important part in the development of schizophrenic psychoses. As a consequence the use of a genetic marker as the HLA system appears to be interesting in determining the disease susceptibility gene of these psychoses. Methods and results of an investigation about the frequencies of 33 HLA alleles observed in 51 patients considered as paranoid schizophrenics are presented. The frequency of HLA-A 29 was diminished while the one of HLA-B 15 was increased but the differences were no longer significant when p was corrected. However when all the results published from 1974 to 1980 were pooled in a combined statistical analysis, some associations became significant. It seems that schizophrenia as a whole, once paranoid and hebephrenic sub-types have to be distinguished. It may be concluded from these data that correlations between schizophrenia and HLA antigens which remain doubtful could be explained with a biological genetic heterogeneity of schizophrenic disorders. Review of literature concerning the identification of HLA haplotypes in schizophrenics pedigrees and about the HLA system as a genetic marker for the clinical response to neuroleptics in schizophrenic patients or in vitro, is also discussed.     

Relationship between HLA antigens and infectious agents in contributing towards the development of Graves' disease

Graves' disease (GD) is an autoimmune thyroid disorder which is associated with the human leucocyte antigens HLA-DR3 and DQA1* O501 in Caucasians. We have explored the possibility that some patients with certain HLA specificities develop anti-HLA antibodies which are correlated with environmental factors that may contribute to the development of GD. We studied 40 GD patients and 157 healthy individuals (controls). Serology was used to type HLA-A, -B, -Cw, and -DR antigens. The frequencies of these antigens in relation to lymphocytotoxic anti-HLA-A-B-Cw-DR antibodies and two environmental factors (Yersinia enterocolitica and Coxsackie B virus) were determined. The frequencies of HLA-B15, -B21 and DR3 antigens were increased, whereas HLA-DR5 antigen was decreased in GD patients. A significant association between HLA-DR3 antigen and lymphocytotoxic antibodies was observed, i.e., IgGs from GD patients were cytotoxic to HLA-DR3+ normal B cells. Following absorption with Yersinia enterocolitica or Coxsackie-B-virus, only Coxsackie-B virus completely inhibited the lymphocytotoxic reactions against HLA-DR3+ B cells. Besides confirming the association of HLA-DR3 with GD, this study also suggests the role of Coxsackie-reactive HLA-DR3 antibodies as contributing factors to the pathogenesis of the disease.     

Persistence of biologic activity after disappearance of propranolol from the serum

In order to study genetic and immunological features which might be important in the pathogenesis of asthma, forty-one ragweed allergic seasonal asthmatics were first matched with forty-one ragweed allergic nonasthmatics on the basis of similar total IgE levels. No significant differences were observed in their sensitivity to ragweed antigen E (measured by histamine release), or in their skin response to ragweed antigens E, Ra3 and Ra5. An increased frequency of HLA-B5 was observed in nonasthmatics as compared to asthmatics (P = 0-03). Although frequencies of HLA-A1 and B8 were also elevated in nonasthmatics and HLA-B40 in asthmatics, these differences were not significant. The forty-one asthmatic patients were than paired with forty-one nonasthmatics patients were then paired with forty-one nonasthmatics on the basis of leucocyte sensitivity to ragweed antigen E. Similar HLA differences were found which were non-significant. No significant difference in total IgE levels were found between the two groups. Whereas no differences in IgE synthesis or antigen sensitivity was found in the two populations, the frequency of HLA antigens needs further study in larger groups.     

Localization of the hemochromatosis gene close to D6S105

The hemochromatosis (HC) gene is known to be linked to HLA-A (6p21.3); however, its precise location has been difficult to determine because of a lack of additional highly polymorphic markers for this region. The recent identification of short tandem repeat sequences (microsatellites) has now provided this area with a number of markers with similar polymorphic index to the HLA serological polymorphisms. Using four microsatellites--D6S105, D6S109, D6S89, and F13A--together with the HLA class I loci HLA-A and HLA-B in 13 large pedigrees clearly segregating for HC, we have been able to refine the location of the HC gene. We identified no recombination between HC and HLA-A or D6S105, and two-point analyses placed the HC gene within one centimorgan (cM) of HLA-A and D6S105 (HLA-A maximum of the lod score [Zmax] of 9.90 at recombination fraction [theta] of 0.0, and D6S105 Zmax of 8.26 at theta of 0.0). The markers HLA-B, D6S109, D6S89, and F13A were separated from the HC locus by recombination, defining the centromeric and telomeric limits for the HC gene as HLA-B and D6S109, respectively. A multipoint map constructed using HLA-B, HLA-A, and D6S109 indicates that the HC gene is located in a region less than 1 cM proximal to HLA-A and less than 1 cM telomeric of HLA-A. These pedigree data indicate an association between HC and specific alleles at HLA-A and D6S105 (i.e., HLA-A3 and D6S105 allele 8).(ABSTRACT TRUNCATED AT 250 WORDS)