bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA antigens and Bf allotypes in lichen sclerosus et atrophicus
Authors: HOLT P. J. A , DARKE C
Published: July 2010

A study of the HLA—A, B and DR antigens and properdin factor B allotypes of 26 patients with lichen sclerosus et atrophicus and a normal control population showed an increase in the HLA—Aw31 antigen only. However, when the HLA—A and B frequencies were combined with the results of a previous independent study a significant increase in both HLA—Aw31 and HLA—B40 was noted. These findings suggest an association between lichen sclerosus et atrophicus and the HLA system.
HLA‐A, B and HLA‐DR phenotypes in Mainland Chinese patients with diabetes mellitus
Authors: LEE T. D , ZHAO T , CHI Z , WONG H , SHEN M , RODEY G
Published: July 2010

HLA‐A, B and DR antigens were studied in Mainland Chinese diabetes mellitus patients and controls (31 Type I DM, 50 Type II DM, 105 controls). HLA‐DR3 and HLA‐A9 were increased in Type I diabetics only. An increase in HLA‐DR4 was noted in Type I diabetics, but the increase was not statistically significant in this small series.
Estimation of haplotype frequencies
Authors: MORTON NEWTON E , SIMPSON S. PATRICIA , LEW RUTH , YEE SHIRLEY
Published: July 2010

Maximum likelihood estimates of haplotype frequencies in multilocus systems are often zero and so may be genetically inacceptable. Estimation problems are discussed, and preferable estimates are derived.
HLA antigens and congenital dislocation of the hip
Authors: ZERVAS J , ZOUBOPOULOS H , CONSTANTOPOULOS C , THEODOROU S. D , TOUBIS M , FESSAS PH
Published: July 2010

The HLA‐A and B phenotypes of 42 Greek children with CDH were determined and compared to those of 400 controls.

A significant deviation of the frequency of the antigen HLA‐A1, (Pc < 0.003) was noted.

It is suggested that immunogenetic factors are contributing to the development of the disease.
An immune response gene linked to MHC in man
Authors: REZNIKOFF‐ETIEVANT M. F , MULLER J. Y , JULIEN F , PATEREAU C
Published: July 2010

With a view to finding a relationship between immune response and MHC in man, 83 D negative mothers with allo‐into‐D antibodies and 26 PLA1 negative mothers with allo‐anti‐PLA1 antibodies were investigated as regards their HLA‐A, B and DR antigens. We have found that there is a highly significant relation between the DR3 antigen and an immune response to the PLA1 antigen, but none to the D antigen.
HLA antigens in pityriasis versicolor
Authors: KANITAKIS J. , GIANNOPOULOS Z. , TOURKANTONIS A. , KANITAKIS C.
Published: July 2010

The distribution of 30 HLA antigens was studied in 48 patients with Pityriasis Versicolor and 134 controls. No significant deviations were found in the patient group after correction for the number of antigens tested.
HLA antigens in patients with adult T‐cell leukemia
Authors: TANAKA K. , SATO H. , OKOCHI K.
Published: July 2010

HLA‐A, B, C, and DR antigens were studied in Japanese patients with adult T‐cell leukemia. No associations were found in comparisons with normal healthy controls.
The impact of HLA‐DR compatibility on cadaver kidney graft survival in a prospective study with special emphasis on the quality of typing
Authors: JAKOBSEN BODIL K. , LANGHOFF ERIK , PLATZ PER , RYDER LARS P. , THAYSEN JØRN HESS , ØLGAARD KLAUS , KRISTENSEN JØRGEN KVIST , JØRGENSEN HANS E. , LØKKEGAARD HANS , RASMUSSEN FINN , SØRENSEN ARNE W. S. , SVEJGAARD ARNE
Published: July 2010

The survival data of 151 consecutive cadaver kidneys transplanted by the two transplantation centres of Copenhagen from September 1, 1980 to September 30, 1982 with an observation period of at least 3 months have been analyzed. The HLA‐DR types could not be established in 4 out of 130 donors. In most of the analyses only the well‐defined antigens DR1, 2, 3, 4, 5, 7, and w8 were included. Inclusions of the DRw6, w9, and w10 antigens in the matching did not change the results. The one‐year graft survival (GS) was 72.1% for 97 HLA‐DR compatible kidneys as compared to 41.4% for 49 incompatible kidneys (p = .0007); this difference remained highly significant when stratified for the recipient status of pretransfusion, risk, and age. Non‐transfused recipients had a fairly good GS but had received significantly better matched kidneys than the remaining recipients. The transfusion “effect” became barely significant (p = .054) when stratified for DR. There was no significant influence of donor or recipient DRw6‐type as defined in this study. The GS was not significantly influenced by HLA‐A, B matching, recipient antibody status, B cell cross‐matches, transplant, or donor centre. Special efforts were made to assign the HLA‐DR phenotypes of the recipients and donors as accurately as possible. In 39 cases, there was a discrepancy between the result of the acute DR‐typing of the donor and the final result based on subsequent typings. The acute DR match had no influence on GS in these recipients whereas the final match had a significant influence in the same group, which in a way comprise a randomized trial. In the total material, the acute DR match still showed an influence on GS, but the significance decreased by a factor 20. This illustrates how the quality of DR typing may influence the results of the analyses. The overall GS (62.5%) was significantly (p = .05) better in this series than that (48.2%) in our preceding series, but it is uncertain whether this is due to better matching alone.
Cytotoxic antibodies in sera of Venezuelan multiparous women of Amerindian and mixed ethnic origin
Authors: SIMONNEY NANCY , LAYRISSE Z. , BALBAS O. , GARCÍA E. , STOIKOW Z.
Published: July 2010

Sera from 464 multiparous women of mixed ethnic origin and 114 Amerindian mothers (Warao of Western Venezuela), were studied for lymphocytotoxicity using a panel of B and T lymphocytes isolated from 50 to 100 individuals from the same populations. Twenty‐five and 9.65% of the sera, respectively, showed activity against at least 5% of the panel. Among the women of mixed ethnic origin 10% produced antibodies directed against one or more HLA Class I antigens while 2 sera contained monospecific anti‐DR antibodies; among the Warao, only 2 sera recognized HLA antigens: a Bw51 and an undetermined Cw antigen which shows linkage disequilibrium with Bw16 in both populations.
HLA and urolithiasis
Authors: BEAR J. C. , CHURCHILL D. N. , MORGAN J. , MARSHALL W. H. , GAULT M. H.
Published: July 2010

Frequencies of persons having particular HLA‐A, ‐B, and ‐C antigens were compared for 113 urolithiasis clinic patients, a subset of 24 patients who had hypercalcuria, and 225 controls. The frequency of HLA‐A30 was significantly elevated among the patients. A suggestion (Säfwenberg et al. 1978) that HLA‐B27 frequency is elevated among hypercalcuric patients with recurrent kidney stones was not confirmed.
HLA and Kaposi's sarcoma in Sardinia
Authors: CONTU L. , CERIMELE D. , PINTUS A. , COTTONI F. , LA NASA G.
Published: July 2010

Twelve Sardinian patients affected by histologically defined classic Kaposi's sarcoma (KS) were HLA‐A, B, C and DR typed.

Compared to 220 age and ethnically matched healthy controls, KS patients showed a significant increase in HLA‐DR5 (66.6 vs 23.1%, P < 0.001) and a considerable decrease in HLA‐DR3 (8.3 vs 53.6%, P = 0.0055).

No definite association was observed for other HLA antigens. These results confirm the existence of an HLA associated genetic control of KS susceptibility and support the hypothesis that HLA‐DR5 plays the role of a predisposition marker while HLA‐DR3 bears a genetic resistance to the disease.
The gene frequency of SB alleles in the Japanese population
Authors: NISHIMURA YASUHARU , YASUDA NORIKAZU , SASAZUKI TAKEHIKO , SHAW STEPHEN
Published: July 2010

The gene frequency (±SD) of SB alleles was estimated in the Japanese population as follows: SB1 0.00, SB2 0.195 ± 0.027, SB3 0.070 ± 0.017, SB4 0.091 ± 0.019, SB5 0.335 ± 0.034 and SB blank 0.308 ± 0.035. The absence of SB1 allele, decrease of SB4 allele and increase of SB5 allele are characteristic features of the SB system in the Japanese population as compared with Caucasians.
Association of HLA specificity LB‐E12 (MB1, DC1, MT1) with lepromatous leprosy in a Venezuelan population
Authors: Ottenhoff T. H. M. , Gonzalez N. M. , Vries R. R. P. de , Convit J. , Rood J. J. van
Published: July 2010

To investigate whether an association could be found between HLA and lepromatous leprosy a population study was performed in Tachira, Venezuela. This was done in the same endemic area in which recently both non‐random parental HLA‐haplotype and preferential segregation of the HLA specificity LB‐E12 (MB1, DC1, MT1) was demonstrated in lepromatous leprosy patients from multicase families. In this study 32 lepromatous patients and 32 healthy controls were typed for HLA‐A, ‐B, ‐C, ‐DR and the specificities MB and MT. The frequency of LB‐E12 (MB1, DC1, MT1) showed a significant increase in lepromatous leprosy patients (p=0.04). This is the first report concerning HLA and leprosy which confirms in the same endemic area an association observed in families on the population level.
HLA antigens in ulcerative colitis: a study in the Sicilian population
Authors: Caruso Calogero , Palmeri Patrizia , Oliva Lorenzo , Orlando Ambrogio , Cottone Mario
Published: July 2010

HLA antigens were investigated in 41 Sicilian patients with ulcerative colitis and in 151 healthy controls. Frequencies of HLA‐B5 and DR2 were increased in the group of patients with ulcerative colitis whereas the DR3 antigen frequency was decreased. However the corrected p values were not significant. Thus, present results indicate that in ulcerative colitis HLA linked genetic factors play a marginal role, if any.
Further antigenic determinants on HLA‐A molecules
Authors: Richiardi P. , Crepaldi T. , Malavasi F. , Olivetti E. , Carbonara A. O.
Published: July 2010

Monoclonal antibodies detect a new polymorphic antigenic determinant shared by HLA‐A2, 3, 28, 29, 30, 31 and w33. This was demonstrated by population and family studies, including an HLA‐A,B recombinant family, and by lysostrip experiments. Competition experiments, measuring the binding of 125I labelled MoAbs to B lymphoblastoid cell lines coated with anti‐HLA conventional alloantisera and MoAbs showed that this new epitope is spatially distant from other known epitopes of A3 molecules and from monomorphic and polymorphic determinants of A2 molecules detected by monoclonal antibodies. On the other hand, anti‐HLA‐A2 polyclonal alloantisera are able to inhibit binding.
HLA antigens in Hirschsprung's disease
Authors: Kogan J. , Wentzel J. , Roberts D. F. , Scott J. E.
Published: July 2010

In 55 children with Hirschsprung's disease, 64 of their normal siblings and 120 other members of their families, HLA‐A, B and C types were examined. The statistical significance of the raised incidence of A1, B14, B37 and Bw35 in the patients disappeared after correction for multiple testing. The levels of homozygosity were very similar in patients and normal controls. The results indicate no direct association of the disease with HLA type.
Immunochemical analysis of class II molecules expressed by a human B cell line with the unusual class II genotype, DR5+, MB1+, (MB3−), MT2+
Authors: Karr Robert W. , Sachs John A. , Festenstein Hilliard
Published: July 2010

The human B lymphoblastoid cell line FPA was established from a consanguineous individual homozygous for the unusual serologically defined Class II genotype, DR5+, MB1+, (MB3‐), MT2+. The MB1 allodeterminant is classically found only in association with DR1, 2, or w6 and DR5 is almost invariably associated with MB3. Class II molecules expressed by this unusual DR5 homozygous cell line have been characterized by immunochemical analysis using two‐dimensional gel electrophoresis. These molecules were isolated from the FPA cell line by anti‐DR5, anti‐MT2, and anti‐MB1 allosera, as well as a monoclonal antibody which defines an MB1‐like determinant. However, an anti‐MB3 alloserum and a monoclonal antibody which defines an MB3‐like determinant did not immunoprecipitate Class II molecules from FPA. These studies document that the MB1 allodeterminant resides on DS molecules from this DR5 cell line and provide additional evidence that MB1 and MB3 are alleles of the same Class II antigen system.
A F(ab')2 fragment blocking study of the HLA‐B14 antigen
Authors: Darke C.
Published: July 2010

The HLA‐B14 antigen exists in two serologically distinct forms termed Bw64 and Bw65. These two B14 subgroups were studied using the ability of F(ab')2 fragments from HLA‐B14 and Bw6 antisera to block the binding of cytotoxic HLA antibodies directed towards the same or an adjacent antigenic site. The findings suggest that the B14 antigen consists of several antigenic determinants some of which are spatially distinct and others which are closely associated. A “common” determinant possessed by both B14 subtypes is proposed which is separate from a Bw64 (or Bw65) site. Additional determinants that B14 shares with B8, B18 and B38/B39 appear to be distinct from the Bw64/Bw65 site, variably associated with the B14 “common” determinant but closely adjoining the Bw6 antigen.
HLA and multiple sclerosis: population and families study
Authors: Govaerts A. , Gony J. , Martin‐Mondière C. , Poirier J. C. , Schmid M. , Schuller E. , Degos J. D. , Dausset J.
Published: July 2010

Association between HLA and multiple sclerosis (MS) was investigated at the population level on 100 MS patients genotyped for HLA‐A, B, C, DR and Bf, Glo, and on 155 patients phenotyped for the same HLA antigens. Association between MS and DR2 was clearly confirmed, although its strength is rather weak. No other genetic marker could be related to the disease, no haplotype nor any allelic combination could be recognized as MS specific, and antigen genotype frequencies among the diseased could not ascertain the mode of inheritance, although dominance is very likely.

Computer analysis between HLA, Bf, Glo and age of the patient, sex, age of onset and evolution of MS, impairment indexes, titres of anti‐DNA and anti‐measles antibodies in CSF did not show any interaction.

Twenty sib pairs and two trios of MS were also studied; they showed no significant distortion with the random distribution of haplotypes. DR2 gene frequency, however, was significantly higher in sib pairs showing one or two haplotypes than in HLA different affected siblings. Three crossing‐overs were identified which suggest where the HLA‐linked MS susceptibility (MSS) gene could be located within the HLA segment, while other epistatic MSS genes or environmental factors are likely to be important.
Study of HLA antigens of the Martinican population
Authors: Monplaisir Nicole , Valette Ignez , Lepage Virginia , Dijon Veronique , Lavocat Elizabeth , Ribal Colette , Raffoux Colette
Published: July 2010

This is the first time a study has been undertaken on the HLA profile of the Martinican population, a population which is essentially the product of intermixture between

African‐Negroes and French Caucasians. Two hundred and thirty‐eight non‐related subjects were typed for the A and B loci, 158 subjects for C locus and 128 for DR locus.

After analysis of our parameters (antigen and gene frequencies, linkage disequili‐bria, etc.) and their comparison to those found in the Black and Caucasian control populations, we came to the conclusion that our racially‐mixed population is closer to the African‐Negro population than to the French Caucasian. A study of the average gene flow enabled us to evaluate the Caucasian contribution as being about 30%. This figure is subject to change inasmuch as racial intermixture continues. Socio‐cultural variables are assumed to play a minimal role, given the high rate of illegitimacy.
Immunogenicity of and immune response to the human platelet antigen Zwa is strongly associated with HLA‐B8 and DR3
Authors: Mueller‐eckhardt C. , Mueller‐eckhardt Gertrud , Wlllen‐ohff Hlldegard , Horz Annelie , Kuenzlen E. , O'neill G. J. , Schendel Dolores J.
Published: July 2010

In a prospective study the immunogenicity of the Zwa antigen during gestation was investigated. Twenty‐six out of 1,211 pregnant women were Zwa negative (2.15%). In 2 out of 23 Zwa negative mothers who delivered Zwa positive children, an antibody to Zwa was detected. To determine the relationship between the immune response of pregnant women towards Zwa and the MHC, the phenotype frequencies of HLA‐A, B, C, DR, and complement BF, C2, C4A, C4B allotypes of “non‐re sponders” without detectable Zwa antibodies (N=20) were compared with a group of “responders”, i.e. Zwa negative mothers giving birth to Zwa positive children with typical neonatal alloimmune thrombocytopenia (NAIT; N=39) and with a normal control population. When compared to the normal control group, “non‐re‐sponders” showed a significant increase of the DRw6 frequency, whereas in the “responder” group HLAA1, B8, DR3, and C4A*QO were significantly elevated. If “non‐responders” and “responders” were directly compared, only B8 and DR3 remained significantly different. The strongest association with a hypothetical immune response gene appeared to exist with DR3.
A monoclonal antibody detecting an HLA‐DQwl‐related determinant
Authors: Raghoebar Joan , Schreuder Geziena M. T. , Schuurman Ruud , Bruning Hans
Published: July 2010

A complement fixing monoclonal antibody (moab) was prepared which reacts with a polymorphic determinant on HLA class II molecules. The moab IIB3 recognises all DQwl (DO, MB1, LB‐E12) positive cells as well as some DR4, DR7, DRw8 and DRw9 positive cells. The moab reacts mainly with B‐cells and not or with only a minority of the monocytes. Segregation of the determinant with HLA‐DR could be shown. The determinant is strongly expressed on DR2, DR4 and DRw6 positive cell lines but only weakly on DR1 lines.

In contrast to a monoclonal antibody against a monomorphic determinant on class II molecules IIB3 did not give a distinct inhibition of the MLC nor did it inhibit the generation of CTLs in MLC as has been described for the DQwl like moab BT 3/4 (Corte et al. 1982). Immunoprecipitation indicates that IIB3 reacts with DQ‐like molecules.
Specific removal of anti‐red cell blood group activity from anti‐HLA lymphocytotoxic sera and purification of anti‐A and anti‐B antibodies with lymphocytotoxic activity
Authors: Bernoco Marietta , Bernoco Domenico , Danilovs John , Terasaki Paul I. , Mollicone Rosella , Oriol Rafael
Published: July 2010

Lymphocytotoxic antibodies to the red cell blood groups A and B were purified from human sera by elution from synthetic immunoadsorbents (Synsorbs from Chembiomed). The lymphocytotoxic activity of the eluted antibodies was better preserved when elution was carried out at pH 11, whereas it was less stable when elution was performed at pH 3. In addition, complete removal of anti‐red cell blood group activity from an anti‐HLA serum was easily obtained by adsorption on the corresponding Synsorb without loss of anti‐HLA activity.
Three‐locus haplotype interactions in the analysis of linkage disequilibrium
Authors: Nijenhuis L. E. , D'amaro J.
Published: July 2010

We have shown that the application of Piazza's formula for the estimation of the “three‐locus interaction delta” should not be used for that purpose. In addition, the method of Porta & McHugh, for the demonstration of haplotype interaction in associations between HLA and disease, leads to completely erroneous conclusions. Other methods of calculation that have been used to analyse haplotype interactions also appear to be based on erroneous concepts.

We suggest that nothing more than the estimation of heterogeneity in simple 2x2 contingency tables should be used for the analysis of linkage disequilibria. This principle is applied to the HLA‐A, ‐B and ‐C haplotype frequency tables of Baur & Danilovs. For the greater part of the HLA‐B alleles, three‐locus haplotype frequencies can be explained from the A, B and the B, C disequilibria, without any further haplotype interactions. The predominant exceptions in that respect are ha‐plotypes containing the B44 allele, which has been shown to contain two subgroups and therefore, we are not justified to conclude that this exceptional behaviour of haplotypes with B44 should be attributed to three‐locus haplotype interactions.
A human helper‐dependent influenza virus‐specific cytotoxic Tlymphocyte clone restricted by HLA‐DR2
Authors: Fleischer Bernhard
Published: July 2010

A human influenza A virus‐specific cytotoxic Tlymphocyte (CTL) clone is described that is restricted by a class II HLA‐antigen. Of a large panel of B‐lympho‐blastoid cell lines (B‐LCL) as target cells the clone lysed only infected cells sharing HLA‐DR2 with the donor of the clone. In cold target inhibition studies only infected cells bearing HLA‐DR2 could inhibit cytotoxicity. Infected PHA‐blasts that express less DR‐antigen than B‐LCL cells were lysed to a much lesser extent though they could be infected equally well. Trypan blue staining and postlabelling of the target cells showed that the clone indeed killed the target cells. The clone did not proliferate in response to infected irradiated autologous LCL cells and had the OKT3+4+8−DR+ phenotype. The possible significance of class II restricted CTL is discussed.
Positive selection of activated T cells of the T8 (CD8) sub‐type by immunomagnetic separation
Authors: Leivestad Torbjørn , Gaudernack Gustav , Ugelstad John , Thorsby Erik
Published: July 2010

By conjugating a monoclonal IgM antibody of CD8‐specificity to magnetite‐containing polymer particles, we have developed a rapid and simple one‐step procedure for positive selection of T8 cells. The method ensured good yield and viability of pure T8 cells. The positively selected T8‐fraction from MLC activated T cells retained their cytolytic capacity and gave a moderate proliferative response. Most of the proliferative response occurred in the negatively selected T4 population which showed only a marginal cytotoxic activity against PHA blasts as target cells. Transferrin receptor expression, as measured in a direct radiobinding assay, could also be demonstrated both among pure T4 and T8 cells upon MLC‐activation.
Development and characterization of a monoclonal antibody to class II MHC antigens in rhesus macaques
Authors: Moore P. F. , Ellingsworth L. R. , Toedter G. P.
Published: July 2010

The characterization of a monoclonal antibody with specificity for a monomorphic determinant on rhesus macaque class II antigens is described. This antibody, designated 2D16, is an IgG2b immunoglobulin which also displayed useful cross‐reactivity with lymphoreticular cells and cell lines of other species including man, bonnet and stumptail macaques, sheep, dog and horse. Limited polymorphism of the 2D16 epitope was observed in the dog.
H‐Y antigen is not expressed on purified rat erythrocytes
Authors: Bradley Mark P. , Baird Margaret A. , Heslop Barbara F.
Published: July 2010

The presence of H‐Y antigen on male rat erythrocytes was investigated using a high‐titre H‐Y antiserum in both ELISA, cellular absorption and syngeneic male to female erythrocyte transfusion studies. No evidence was found to suggest that H‐Y antigen is expressed on rat erythrocytes. These data are in accord with recent findings of other investigators studying mouse H‐Y serology.
HLA antigens and complement types in patients with intracranial saccular aneurysms
Authors: ØStergaard J. R. , Bruun‐Petersen G. , Lamm L. U.
Published: July 2010

The occurrence of HLA‐A, ‐B, ‐C antigens and the HLA controlled complement factors (Bf, C2, C4) was investigated in an unselected group of 116 consecutively admitted patients with intracranial saccular aneurysms, and compared to that of healthy controls (blood donors). When multiplying the p‐values with the number of comparisons made, none remained significant. However, a rather high etiologic fraction of the BfS gene (0.59) was obtained. Moreover, for HLA ‐B7 a significant deviation from the Hardy‐Weinberg equilibrium with an increase of homozygotes was found. Due to linkage disequilibria this could indicate a strong association between HLA‐DR2 and saccular aneurysms. The presence of HLA‐DR2 was therefore investigated in a series of 15 aneurysm patients used as cadaver kidney donors and not included among the 116 consecutively admitted patients. In this group the HLA‐DR2 antigen frequency was significantly increased (66.7% vs. 29.7%, p < 0.01). The present study thus demonstrates an association of saccular aneurysm and the major histocompatibility complex and shows the existence of a genetic predisposition to saccular aneurysm.
HLA‐B POT: a new HLA‐antigen within the B7‐cross reactive group
Authors: Reekers P. , van der Beucken M. , Andrien M. , Beelen J. , Mueller‐Eckhardt G. , Th. Schreuder G. M.
Published: July 2010

In this report, a new HLA‐B locus antigen is described (tentatively called POT). The antigen has been identified with antisera against the antigens that belong to the B7‐cross reacting group.

In a collaborative study, based on exchange of cells and sera, it was confirmed by population and family studies that the antigen is distinct from B7, Bw42 or Bw73 and is associated with Bw6.

In absorption experiments with EBV‐transformed cell lines, the POT‐antigens removes preferentially anti‐B7, Bw42 and Bw73 activity and to a lesser extent antibodies reactive with the B40 CREG‐antigens.
Impaired lymphocyte responsiveness to phytohaemagglutinin associated with the possession of HLA‐B8/DR3
Authors: Amer A. , Singh G. , Darke C. , Dolby A. E.
Published: July 2010

An examination was made of blastogenic response to phytohaemagglutinin (PHA) in HLA‐B8 and/or DR3 positive subjects and B8/DR3 negative individuals. Both B8 and DR3 antigens were associated with a depression of the response at all three doses of PHA used. The possession of both these antigens did not lead to a further depression of the response.
An overview of the restriction fragment length polymorphism of the HLA‐D region: its application to individual D‐, DR‐ typing by computerized analyses
Authors: Tilanus Marcel G. J. , Hongming Fei , van Eggermond Marja C. J. A. , Bijl Mara v.d. , D'Amaro Joe , Th. Schreuder Geziena M. , de Vries René R. P. , Giphart Marius J.
Published: July 2010

HLA‐D/DR alleles as defined by cellular and serological typing can also be identified by biochemical methods. The Southern blot technique provides an additional typing facility which can be applied to DNA obtained from any source of nucleated cells. The polymorphism revealed by Southern blot analyses, the so‐called restriction fragment length polymorphism (RFLP), depends upon the restriction enzyme and cDNA probes used. To identify HLA‐DR specificities a protocol was developed based on the use of the results of southern blot analyses with several restriction enzymes and cDNA probes within a panel of HLA‐D/DR homozygous cells representing the DR1 to DRw8 alleles.

First, hybridizations with the 3’untranslated sequence of the DRβ cDNA probe, after digestion of the DNA with PvuII (PvuII‐DRβ3′) allows the selective identification of DR1, DR2 and DRw8; DR3, DR5 and DRw6 are found as one group as well as DR4 and DR7 as another. Second, TaqI‐DQα hybridization allows the splitting of DRw6‐Dw18, DRw6‐Dw19 and DRw6‐Dw9 from the DR3, DR5 and DRw6 group. The other alleles DR3, DR4, DR5, DRw6‐Dw16 and DR7 are revealed by dehybridization and rehybridization of the blot with a DRβ cDNA probe. This protocol was used to test whether in a panel of 30 randomly chosen individuals the HLA‐DR typing could be performed. The results were highly concordant to the serotyping. Furthermore by adding the Pst‐DRβ and TaqI‐DQα RFLPs, most of the MLC defined Dw specificities could also be identified. An overview of the specific fragments described here has been summarized in matrices which can be used as references for DNA‐typing in computerized analyses.
Increased frequency of HLA‐DPw2 in pauciarticular onset juvenile chronic arthritis
Authors: ØDum Niels , Morling Niels , Friis Johannes , Heilmann Carsten , Hyldig‐Nielsen Jens J. , Jakobsen Bodil K. , Pedersen Freddy Karup , Platz Per , Ryder Lars P. , Svejgaard Arne
Published: July 2010

Thirty‐six unrelated Danish patients with pauciarticular Juvenile Chronic Arthritis (PJCA) and 120 controls were typed for HLA‐DPw1‐w6 and the local specificity CDPHEI with bulk‐expanded Primed Lymphocyte Typing (PLT) cells. The frequency of HLA‐DPw2 was 52.8% in PJCA patients and 16.7% in controls (relative risk, RR = 4.5; P < 0.001). The antigens HLA‐Dw5 and/or Dw8 were present in 50% of the patients and in 21.3% of the controls (RR = 4.2; p < 10‐3). DPw2 was not associated (in linkage disequilibrium) with Dw5/w8 in patients or in controls, and the DP and D associations with PJAC were independent of each other. However, the combined presence of DPw2 and Dw5 and/or Dw8 gave a significantly higher risk of PJCA than each antigen alone indicating interaction of DP and DR gene products. PJCA is the first disease definitely found to be associated with a DP antigen.
HLA phenotypes and bullous cutaneous reactions to drugs
Authors: Roujeau Jean‐Claude , Bracq Christine , Huyn Nhan Thien , Chaussalet Edith , Raffin Chantal , Duédari Najib
Published: July 2010

Drug induced toxic epidermal necrolysis and Stevens‐Johnson syndrome are weakly associated with HLA‐B12. Among patients reacting to a given drug we observed stronger links, especially for HLA‐A29; B12; DR7 and sulphonamides.
Class II MHC antigen (HLA‐DR) expression in the developing sweat gland
Authors: Lampert I. A. , Easty D. , Evans D. J.
Published: July 2010

Class II MHC antigen (HLA‐DR) is a normal constituent of the ductular lining cells of the sweat gland. In development, HLA‐DR is first expressed on the developing bud of the growing gland as it extends down from the epidermis. The cells immediately behind the bud lose this staining. The antigen subsequently appears on the ductular lining cells and extends from the acrosyringium down the full length of the duct. The coils are negative. The appearance of the antigen in these two different situations suggests that it has a role both in embryogenesis and in the normal functioning of the mature gland.
HLA class I and II typing using cells positively selected from blood by immunomagnetic isolation ‐ a fast and reliable technique
Authors: Vartdal Frode , Gaudernack Gustav , Funderud Steinar , Bratlie Anne , Lea Tor , Ugelstad John , Thorsby Erik
Published: July 2010

This paper describes a new cell isolation and HLA typing technique, which permits cell separation and HLA class I or class II typing to be performed in 70 min. Magnetic monodisperse microspheres (Dynabeads TM) were coated with monoclonal antibodies (MAbs) specific for the CD8 T cell antigen or for HLA class II monomorphic epitopes. They could then be used to obtain HLA class I or class II positive cells directly from ACD blood in approximately 15 min by the use of magnetic separation. The cells (attached to the microspheres) were subsequently used in microcytotoxic HLA typing (total incubation time of 55 min) using acridin orange/ethidiumbromide to stain viable (yellow) and dead (red) cells. It was found that this immunomagnetic (IM) HLA typing technique was specific, has a sensitivity superior to that observed for conventional microcytotoxicity assays and gave low background staining. IM HLA‐ABC typing of 50 healthy donors and 10 patients and IM HLA‐DR typing of 25 healthy donors and 30 patients gave results corresponding well with that obtained independently by conventional HLA typing (concordancy rates 92–100%). Furthermore, the IM HLA typing technique permitted reliable HLA class II typing of blood cells from six patients where conventional HLA class II typing was impossible. The IM HLA typing technique also enables HLA class I and II typing to be quickly and reliably performed on cells from ACD blood of cadaveric donors.
Announcement
Authors: Farewell V. T. , Ladiges W. C.
Published: July 2010

When a number of families can be identified with two or more siblings having a particular disease, Green & Woodrow proposed a test for MHC‐disease association. An extension of this test is presented to detect more general associations when family sizes exceed three.
Assignment of determinants recognized by human alloantisera to HLA‐D‐subregion molecules by a lysostrip technique
Authors: Nuńtez Gabriel , Stastny Peter
Published: July 2010

We have used a lysostripping technique to investigate the molecular relationships of the determinants recognized by human alloantisera and murine monoclonal antibodies reactive with HLA‐D region products. Cytotoxicity mediated by sera that define the specificities DR1, DR2, DR3, DR4, DR7, DRw11, DRw12, DRw13, DRw14, DRw52 and DRw53 was inhibited by anti‐DR but not by anti‐DQ Mabs. In contrast, sera that define DQw1, DQw2 and DQw3 were inhibited by anti‐DQ but not anti‐DR monoclonal antibodies. We found some sera used to define DR specificities that were not inhibited by monoclonal anti‐DR. Cytotoxicity mediated by monoclonal antibodies reactive with the recently described specificities TA10 and MCI was inhibited by anti‐DQ and anti‐DR monoclonal antibodies, respectively. The lysostripping technique is useful for the assignment of specific determinants to HLA‐D subregion molecules.
A new homozygous typing cell with HLA‐D“H” (DB6) specificity
Authors: Jakobsen Bodil K. , Platz Per , Ryder Lars P. , Svejgaard Arne
Published: July 2010

A new homozygous typing cell (HTC), SK is described. Mixed leukocyte culture (MLC) showed that SK is homozygous for HLA‐D“H” (DB6) defined by the HTC, Herluf, and that the HLA‐D typing results obtained by Herluf and SK are highly significantly correlated (Kendall's R = 0.46, p = 2.5 ± 10–5). Both Herluf and SK are also homozygous for a new class II determinant, DN‐1, defined by the monoclonal anti‐B‐lymphocyte antibody, 9w925, developed by Aizawa. The corresponding DN‐1 antigen was present in 2.2% of 136 random, unrelated Danes and in all of six unrelated HLA‐D“H” positive but in none of 20 HLA‐D“H” negative individuals. Thus, there is an absolute and highly significant (p = 4 ± 10–6) association between the cellularly defined HLA‐D“H” determinant and the serologically defined DN‐1 antigen, which strongly suggests that HLA‐D“H” can now be detected serologically. DN‐1 may be identical to DRw12 which is, however, poorly defined. The HTC‐donor SK was immunized by pregnancy, and her serum contains anti‐HLA‐B7, which can easily be absorbed, and anti‐B‐lymphocyte antibodies which reacted with cells from 87.7% of 536 unrelated Danes. The reaction pattern of this serum is negatively associated with DR3, w6, and w8. This serum may define a new broad, cross‐reacting antigen belonging to the same group as DRw52 and DRw53 or DQw1‐w3, but it is clearly different from each of these antigens.
Epitope analysis with monoclonal antibodies directed against class II molecules subdivides HLA‐DR2, DR3 and DR4: correlations with cellularly defined Dw specificities
Authors: Johnson Judith P. , Nordwig Hellmuth , Wank Rudolf
Published: July 2010

Monoclonal antibodies (Mabs) defining 14 distinct polymorphic epitopes have been produced against the class II antigens of HLA‐DR3Dw3DQw2 cells. Population analysis indicates that Mab C1 is directed against the DQw2 specificity and Mab M6 against the DRw52 specificity. The remaining Mabs define epitopes shared by the class II molecules of DR3 and various other specificities. Seven DR3Dw3 DQw2 haplotypes were examined and could be divided into two types based on the presence of the epitope defined by Mab M3. Analysis of DR2 and DR4 homozygous cells with these Mabs revealed several distinct patterns of epitope expression. These subdivisions were found to correlate with the cellularly defined Dw specificities.
The human sex ratio: increase in first‐born males to parents with shared HLA‐DR antigens
Authors: Radvany R. M. , Vaisrub N. , Ober C. , Patel K. M. , Hecht F.
Published: July 2010

Maternal‐fetal HLA‐DR antigen sharing has been reported to affect the sex ratio of first‐born. We therefore studied offspring sex ratios and birth orders in 66 families in which parents shared one or more HLA‐DR antigens as compared to 61 families with no parental HLA‐DR sharing. A significant excess of males was found among first‐born children who were HLA‐DR compatible with their mothers compared to first‐born HLA‐DR in compatible children of (a) couples sharing HLA‐DR antigens and (b) couples not sharing HLA‐DR antigens. Increased numbers of males may persist among children of higher birth orders in families where parents share both HLA‐DR antigens, but not among couples sharing only one HLA‐DR antigen. We hypothesize that the presence of the H‐Y antigen in the male fetus may provide the necessary stimulus for a successful pregnancy in HLA‐DR compatible pregnancies and may explain the excess of male births in the general population.
Frequency and associations of HLA‐DR and HLA‐DQ antigens in a British Caucasoid panel
Authors: Awad J. , Navarrete C. , Festenstein H.
Published: July 2010

The frequencies of the HLA‐DR and ‐DQ antigens, including those of the new specificities “DRBr” and TA10, were established in a random panel of 286 British Caucasoids. The most frequent DR antigens were DR2, DR4 and DR7. The DR‐DQ antigen associations were examined and the only heterogeneity found was with DR7 which was found to be associated predominantly with DQw2 but also with DQw3. The DR4's were subdivided into those positive and those negative for TA10 and DR4‐TA10 was found to be associated with HLA‐B44.
HLA‐A, B and DR antigen frequencies in patients with AIDS‐related persistent generalized lymphadenopathy (PGL) and thrombocytopenia
Authors: Raffoux C. , David V. , Couderc L. D. , Rabian C. , Clauvel J. P. , Seligmann M. , Colombani J.
Published: July 2010

HLA‐A, B, DR phenotype frequencies were studied in 69 homosexual patients with persistent generalized lymphadenopathy (PGL), in 8 patients with LAV/HTLV III related thrombocytopenic purpura and in 21 homosexual controls. Antigen DR5 was significantly increased in PGL patient groups as compared to controls. Our findings suggest that genetic factors associated with HLA‐DR5 antigen may predispose individuals infected by the LAV/HTLV III virus to the occurrence of PGL and/or thrombocytopenia.
Expression of class I‐MHC antigens by cultured human epidermis and epidermal allografts
Authors: Mauduit G. , Vincen CL. , Gielen V. , Faure M. , Demidem A. , Thivolet J.
Published: July 2010

In vitro grown class II‐MHC antigen free epidermal sheets were used as epidermal allografts (EAG) across a major histocompatibility barrier in 20 non‐immuno‐suppressed recipients suffering from leg ulcers.

Class I antigens were expressed on cell membranes of basal cell layer only on the epidermal sheets. After grafting, patchy areas of membrane fluorescence were observed among cells from the suprabasal layers on the epidermis from skin biopsies taken between days 5 and 28. All cells of the basal and the suprabasal layers expressed class I antigens on biopsies taken after day 28, as on normal human epider. mis.

This work demonstrates that class I antigens are expressed by epidermal cells in cultures used for grafting. The absence of rejection cannot be explained by the absence of class I‐MHC antigens in EAG.
Cellular and serological subtypes of HLA‐DR2
Authors: Freidel A. C. , Betuel H. , Gebuhrer L. , Farre A. , Lambert J.
Published: July 2010

HLA‐DR2 and its subtypes were investigated in informative families and unrelated Caucasoid individuals. Serological and cellular typing indicate that DR2 can be divided into DR2 long and DR2 short (sh), each of which can be further subdivided either by HLA‐D typing or primed lymphocyte reagents. DR2 long includes Dw2, Dw12 and a new subtype temporarily called D‐GEN. The cellular equivalent of DR2sh was recognized by mixed lymphocyte culture (MLC) practised in a family (family FJO); the typing cell individualized was termed FJO. The reactivity of this cell is compared with similar DR2sh varieties described in other laboratories: MN2 (Bach, Minneapolis), AZH (Brautbar, Jerusalem), DB9 (Layrisse, Caracas). The distinction between FJO, MN2 and AZH is not clear, suggesting the existence of shared epitopes; DB9 cells gave typing responses only in family FJO but typed no one else in our panel. Primed cellular reagents FJO anti Dw2 and Dw2 anti FJO when tested against DR2 subtypes support the distinction between DR2 long and DR2sh. The use of these subgroups of DR2 in functional studies, the biochemical analysis of their class II molecules, the pattern of their DNA recombinant fragments and the correlation established with some diseases will be discussed, since they further contribute to the cleavage between DR2 subtypes.
Differential expression of HLA‐DR allospecificities on antigen specific T cell clones
Authors: Igarashi M. , Suciu‐Foca N. , Ferrone S.
Published: July 2010

Serological and immunochemical analysis of T cell clones generated from an HLA‐DR3, DR7 donor detected a lower expression of HLA‐DR3 than of HLA‐DR7 antigen. The defect in the expression of HLA‐DR3 antigen appears to reflect abnormalities in regulatory mechanism(s), since the cell surface expression of this antigen could be increased by infecting T cell clones with human T lymphotropic virus I. This finding was paralleled by an increase in the level of mRNA encoded by the HLA‐DR β gene.
Recombinant γ interferon induces class II major histocompatibility complex antigens on insulinoma cells
Authors: Vliet E. , Molenaar J. L. , Tuk C. W. , Bruining G. J. , Vries R. R. P.
Published: July 2010

Aberrant expression of major histocompatibility (MHC) antigens has been implicated as a factor contributing to organ‐specific autoimmunity, such as progressive loss of pancreatic beta cells in type 1 diabetes. We investigated the potential of a rat beta cell tumour, RINMSF, to express enhanced levels of MHC antigens in vifro. To this purpose we treated RINMSF cells in virro with recombinant rat y interferon (rIFγ). We used monoclonal antibodies to RT1.A (class I) and RT1.B (class II) antigens of the rat MHC in conjunction with flow cytometry and immunoperoxidase techniques to analyse the expression of MHC antigens. Untreated RINMSF cells express low levels of RTl.A, whereas they, are negative for RT1.B. Treatment with rlFγ appeared to increase the expression of RT1.A antigens substantially. Most importantly. RT1.B antigens were newly expressed by rat insulinoma cells in vilro after treatment with rlFγ. To our knowledge this is the first documentation of the potential of beta cells or their derivatives to express class I1 MHC antigens following IFγ‐treatment. This mechanism may play an important role in the augmentation and perpetuation of insulitis leading to type 1 diabetes mellitus.
Generation and characterization of three new monoclonal antibodies detecting the allospecificities HLA‐A2, w69, HLA‐A3 and HLA‐B13
Authors: Eiermann T. H. , Raghavachar A. , Woulpl A. , Ballas M. , Fischer M. , Goldmann S. F.
Published: July 2010

Immunization of balb/c mice with peripheral blood mononuclear cells of a leukemic patient possessing the antigens HLA‐A2,3; B7,35 resulted in the polymorphic monoclonal antibody (moab) UL‐101/68 (IgM) defining HLA‐A3. Immunization of a second group of balb/c mice with the lymphoblastoid cell line BER homozygous for HLA‐A2; B13 revealed two polymorphic moabs UL‐39/10 (IgG3) specific for HLA‐B13 and UL‐39/24 (IgG2b) defining HLA‐A2, w69. Immunoprecipitation and polyacrylamide gel electrophoresis with the two moabs of the IgG isotype confirmed the class I structure of the recognized antigens.
HLA‐A,B,C and DR antigens in a sample of the Tunisian population
Authors: Ayed KH. , Bardi R. , Gebuhrer L. , Gorgi Y. , Betuel H.
Published: July 2010

The HLA‐A, B and DR phenotypes of 109 unrelated Tunisian individuals have been determined. The HLA‐A and B antigen frequencies were compared with data reported for European Caucasoids and various Arab populations.

Most similarities in antigen frequencies were seen between Tunisians and Kabyles from North Africa. A high frequency of HLA‐A23 and HLA‐Bw50 was observed in Tunisians and all Arab populations. A very close similarity in HLA‐DR antigen frequencies exists between Tunisians and European Caucasoids. Linkage disequilibria between alleles of HLA loci were examined; many instances of previously reported antigen associations were seen in Tunisians, together with a number of associations which have not been described elsewhere. Aw34B8 and A2DRw14 are suggested as being common haplotypes in Tunisians.
Binding, uptake and degradation of human recombinant interleukin‐2 (125 ala) in activated human T‐ and B‐lymphocytes and in monocyte‐macrophages
Authors: Petersen C. M. , Christiansen B. S. , Kaltoft K.
Published: July 2010

High‐affinity receptors for IL‐2 (ala 125) were demonstrated in PHA‐, antigenandor alloantigen‐activated human T‐cells (both proliferative and cytotoxic), in PWM‐activated human B‐cells and in human monocyte‐macrophages.

Binding in PHA‐blasts was irreversible and Ca++‐independent, and labelled IL‐2 (ala 125) bound at 4°C could not be removed by trypsin treatment. Binding was strongly pH‐dependent, and lowering of pH caused release of nearly all cell associated radioactivity at 4°C. In T‐ and B‐lymphocytes, additional binding at high ligand concentrations was accounted for by receptors of much lower affinity. Binding lo low‐affinity receptors appeared reversible. At 4°C, 2.2 pM labelled IL‐2 (ala 125) bound to PHA‐blasts (3.6 × 106/ml) with a half time of about 15 min, and the association rate constant was approximately 8 × 109 M‐1 min‐1. The number of high affinity receptors per T‐cell was determined as 9.7 ± 0.5 × 102.

At 37°C, 60% of the tracer bound at 4°C was rapidly internalized (Kint = 0.89 × 10‐1 min‐1), and radioactivity comprising small MW products and iodotyrosine was released following a sigmoidal curve after a 20 min lag period. Similar results were obtained in PWM‐activated B‐lymphocytes and in cultured monocytes.

It is concluded that high‐affinity receptors mediate binding, uptake and degradation of IL‐2 in activated human T‐ and B‐lymphocytes and in monocyte‐macrophages.
Susceptibility to human cutaneous leishmaniasis and HLA, Gm, Km markers
Authors: Barbier D. , Demenais F. , Lefait J. F. , David B. , Blanc M. , Hors J. , Feingold N.
Published: July 2010

A relationship between markers related to the immune response (HLA system, Gm and Km immunoglobulin allotypes) and susceptibility to cutaneous leishmaniasis was investigated in a population of Hmong refugees who had recently settled in French Guiana. Two approaches were used: 1) case/control comparisons of the marker phenotype distribution to detect possible associations; 2) multiple‐case family studies to search for marker‐linked genes. When the distribution of HLA‐A, B, C, antigens and Gm, Km allotypes was compared between patients and controls, only a significant decrease of HLA‐Cw7 antigen among leishmaniasis patients was detected (p = 0.01). No interaction between any two of these markers and the disease was found. On the other hand, neither an HLA, Gm or Km susceptibility gene could be demonstrated in the informative sets of affected siblings. These results are discussed with respect to those reported in other infectious diseases.
Two alleles detected for HLA‐DZα on the basis of a polymorphic restriction site in the third exon
Authors: Bosch M. L. , Slierendregt B. L. , Tilanus M. G. J. , Giphart M. J.
Published: July 2010

The restriction enzyme ApaI has been used to define Restriction Fragment Length Polymorphism (RFLP) within the DZα gene. Digestion of genomic DNA of 96 individuals with ApaI reveals the existence of two different patterns. Both homozygous and heterozygous individuals were detected. Hardy‐Weinberg analysis indicates that DZα is part of a di‐allelic system with allele frequencies of 50%. DZα polymorphism in the population studied does not correlate with serologically determined class I and HLA‐DR, DQ and cellular DP typing data. A limited family study demonstrates that DZα polymorphism segregates with HLA‐class II phenotypes.