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Results for “HLA-DR6 Antigen”

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At least 19 recordsLinked to original sources
PubMed1990

HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients.

This study of 110 seropositive rheumatoid arthritis (RA) patients confirms the significant association of susceptibility to RA with HLA-DR4 specificity (P less than 0.001). The DR1 frequency is elevated in the entire seropositive patient group, reaching marginal significance (P less than 0.025). The DR4-negative patients, however, have a much higher prevalence of DR1 (P less than 0.001). Surprisingly, the DRw6 specificity is significantly increased in the remaining DR4- and DR1-negative patients (P less than 0.01). These results demonstrate that RA is not associated with a single HLA-specificity, but to various degrees with DR4, DR1, and DRw6. These findings, and particularly the newly recognized association with DRw6, support the hypothesis that functionally equivalent shared epitopes or conformations on otherwise distinct MHC molecules may confer risk for developing RA.

Arthritis, Rheumatoid↗
PubMed1992

Pemphigus vulgaris in siblings: HLA-DR4 and HLA-DQw3 and susceptibility to pemphigus.

BACKGROUND: The association of pemphigus vulgaris with the HLA serotypes, DR4 and DRw6, and with the DQ-beta chain alleles, DQw1 and DQw3, suggests that there is a genetic predisposition to this disease. However, familial cases of pemphigus vulgaris are exceedingly rare. OBJECTIVE: We studied two siblings with pemphigus vulgaris and three unaffected family members to determine whether an HLA allele was associated with the development of pemphigus vulgaris in this family. METHODS: We utilized restriction fragment length polymorphism methods using the HLA-DR beta 1, HLA-DQ alpha, and HLA-DW beta 1 genes as cDNA probes. RESULTS: We found that the affected siblings share the haplotype HLA-DR4 and the DQw.3.2 allele. CONCLUSION: Our findings of gene sharing among siblings with pemphigus vulgaris lend support to previous studies of unrelated Caucasian patients, which implicated DQw3 allele polymorphisms in conferring susceptibility to pemphigus.

Adult↗
PubMed1990

The complexity of DRw6 and DR5 haplotypes in American blacks demonstrated by serology, cellular typing, and restriction fragment length polymorphism analysis.

This study describes the diversity of DRw6 and DR5 haplotypes in the American black population using serology, cellular typing, and restriction fragment length polymorphism (RFLP) analysis. DRw6 (DRw13 and DRw14) and DR5 (DRw11 and DRw12) haplotypes are observed at a high frequency in this population (DRw6: 32%, DR5: 30%). Many of these haplotypes express undefined HLA-D specificities and unusual DQ and DRw52 associations which previously have not been well characterized or reported (e.g., DRw13, DQw5, DRw52c, D-; DRw13, DQw2, DRw52a, D-; DRw11, DQw5, DRw52c, D-). Serologic analysis of class II alleles in American blacks suggests the presence of DRw13, DRw11 and DQw6 allelic variants and demonstrates the difficulty in defining DRw6 and DR5 in this population. The class II genes from four American black families expressing many of the novel DRw13, DRw14, DRw11, and DRw12 haplotypes defined by serology and mixed leukocyte culture were further characterized by RFLP analysis. The data presented here along with other published data identify at least eight DRw13 haplotypes (DRw13A-DRw13H) in the human population. Five of these haplotypes exhibit an undefined HLA-D specificity. Three DRw14 haplotypes (DRw14A-DRw14C) and eight DR5 haplotypes (DRw11A-DRw11E and DRw12A-DRw12C) were also identified. The novel DRw6 and DR5 haplotypes observed in American blacks may arise from differences in DRB1, DQA1, and DQB1 genes as well as from differences in the combinations of alleles of these genes encoded by a haplotype. The serologic and RFLP analyses suggest that some DRw13 and DRw11 haplotypes represent transitional steps between DRw13 and DRw11 in the evolutionary pathway which generated the DRw52 family.

Antibodies, Monoclonal↗
PubMed1991

Serology, restriction fragment length polymorphism, and sequence analysis of a unique HLA class II antigen, DR5x6.

We analyzed a new class II HLA haplotype, which we have designated DR5x6, by serology, restriction fragment length polymorphism (RFLP), and sequence analysis. As the name DR5x6 implies, the antigen is serologically closely related to both DR5 and DRw6. RFLP analysis of this haplotype suggests a close similarity with DRw11 haplotypes. The DNA sequences encoded by the second exon of its DRB1, DRB3, and DQB1 genes were also determined. Comparison of these sequences with those of alleles at these loci in other haplotypes suggests that this haplotype could have evolved from a DRw11 ancestor haplotype (DRw11-DRw52b (Dw25)-DQw7) by means of: (a) a gene conversion at the DRB1 locus involving DRw8 (Dw8.3) as the sequence donor, plus a point mutation or a gene conversion involving DR4-Dw4; and (b) a recombination event by which this haplotype would have acquired the DRw5a (Dw24) allele at the DRB3 locus.

Base Sequence↗
PubMed1990

HLA-A, B, C and DR antigens in nickel contact sensitivity.

The relationship between HLA antigens (A, B, C and DR) and nickel contact sensitivity was examined in 54 patients with contact allergy, as confirmed by an unequivocal positive patch-test reaction only to nickel. A control group was 320 healthy blood donors from the same geographical area as the patients. The HLA-A, B, C and DR antigens were typed using standard serological methods. HLA typing revealed a significant increase of HLA-DRw6 antigen in the patient group (corrected P less than 0.025) and the relative risk for patients with DRw6 to develop nickel sensitivity was 3.32.

Adolescent↗
PubMed1990

HLA associations in patients with polycystic ovaries and in patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.

Ninety-nine Caucasian patients with ultrasonically detected polycystic ovaries (PCO) were typed for human leucocyte (HLA) antigens. Fifty patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency were similarly typed. Among the patients with PCO, there was a significant increase in the frequency of HLA DRW6 (P = 0.0027) compared with that found in a control population, which remained significant (P = 0.027) when corrected for the number of antigens tested. This difference was reduced, but remained significant (P = 0.006), when the patients with CAH and PCO were added. There was also a significant decrease in the frequency of HLA DR7 (P = 0.017) among the patients with PCO compared with a control population, but there was no distortion of the frequencies of HLA A, B or Cw antigens. Among the patients with CAH, previously well documented associations of HLA B14 and DR1 with non-classical disease were confirmed. The frequency of HLA Bw47 was increased among the whole group of CAH patients (P = 0.05) but was not increased among those with classical salt-wasting (SW) or simple virilizing (SV) disease. Family studies were performed in close female relatives of 16 of the PCO patients and 21 of the CAH patients but no evidence for genetic linkage between HLA and PCO status could be found. These data suggest that there is no significant component of disturbed adrenal steroid 21-hydroxylase activity to account for the PCO morphology, although there may be some other genetic factor, more proximal to the centromere on chromosome 6, affecting the development of polycystic ovaries.

Adrenal Hyperplasia, Congenital↗
PubMed1992

HLA-DRw52-associated DRB1 alleles: identification using polymerase chain reaction-amplified DNA, sequence-specific oligonucleotide probes, and a chemiluminescent detection system.

Polymerase chain reaction (PCR) primers were designed to specifically amplify exon 2 of the DRw52-associated DRB1 alleles for subsequent typing by sequence-specific oligonucleotide probe (SSOP) hybridization and chemiluminescent detection. The DRw52 DRB1 group, encoding 22 of the 44 W.H.O. designated DRB1 allelic products, was divided by differential PCR with two polymorphism-directed forward primers. Based on a polymorphism at codon 13, these forward primers separate the DRw52-associated alleles into subsets; one comprised of the alleles of DR3/DRw11/DRw6 and the other of DRw8/DRw12/DRB1*1404. The DRB1 alleles in the latter subset were then defined by SSOP hybridization to the amplified DNA. The preferential amplification also resulted in SSOP definition of 15 alleles in the DR3/DRw11/DRw6 subset but some DRw11/DRw13 heterozygous allelic combinations were still unresolved. Two reverse PCR primers specific for the polymorphism at codon 86 were used to obtain amplified material to which SSOP reactivity provided definitive identification of the ambiguous heterozygotes.

Adult↗
PubMed1992

One-step molecular HLA-DR prescreening employing a set of 14 sequence specific oligonucleotides in a non-radioactive tetramethylammonium chloride hybridization protocol.

A novel non-radioactive protocol for molecular generic HLA-DR typing is introduced, employing sequence specific oligonucleotides (SSOs) enzymatically 3'-labelled with biotin-14-dATP via terminal deoxynucleotidyltransferase in a tetramethylammonium chloride hybridization procedure. The detection reaction is carried out, using streptavidin conjugated horseradish peroxidase which is bound to the SSOs, in combination with a light emitting detection system. Fourteen SSOs and one control SSO are employed for generic HLA-DR typing in a one-step protocol. In order to demonstrate the suitability of this procedure, 5 homozygous typing cell lines and samples of 11 pretyped individuals which include most serologically defined HLA-DR specificities (DR1, 2, 3, 4, 11, 12, 6, 7, 8, 9, 10, 52, and DR53) are analysed with the panel of 14 SSOs. The typing results show that this protocol, which avoids the use of radioisotopes, combines high specificity and easy handling. It also allows typing of poorly amplified samples because even after longer exposition times no false positive signals were observed and is particularly suitable for routine molecular HLA-DR typing on the generic level. In addition it can easily be adapted to DP and DQ typing or DR subtyping.

Base Sequence↗
PubMed1992

About DR beta-restriction fragment length polymorphism (RFLP) analysis in kidney transplantation in connection with a paediatric patient.

A retrospective analysis of the HLA-DR antigens was performed at the DR beta DNA locus by the means of restriction fragment length polymorphism (RFLP) in the case of a two-times kidney transplanted paediatric patient and in 16 adult kidney donor recipient pairs in order to prove the importance of DNA molecular analysis in those cases where the serological identification is poor. The child and her grafts (first from her mother, the second from a cadaver donor) carried the DRw6 antigen which serologically can very poorly be defined. According to DR serotyping before transplantation both the child and the cadaver kidney proved to be DR5, 6, while the DNA analysis revealed mismatches; the child possessed the two subtypes: 13b1 and 14a of the DRw6 antigen only and none of the DR5, the cadaver kidney proved to belong to the DR4 antigen group instead of DR5, and furthermore to a different subtype of the DRw6 (13a3) than the recipient. The DNA analysis of other 16 adult donor-recipient pairs also underlined the importance of the DR beta RFLP analysis in cases where the transplantation antigens could be poorly defined.

Adult↗
PubMed1991

HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6.

The distribution of HLA class II (DR, DQ, and DP) antigens was studied in 41 patients with symptomatic sarcoidosis (SA) and ethnically matched healthy controls. HLA-DR, -DQw1 and -DQw3 typings were performed with alloantisera in the conventional microcytotoxic test, whereas -DP typings were done using primed lymphocyte typing. The frequencies of DRw6 were 41.5% in SA patients and 17.9% in controls (relative risk, RR = 3.2, p = 0.00087, p less than 0.05 when corrected). DR3 was decreased to 14.6% in SA patients compared to 25.9% in controls (RR = 0.49, p = 0.07, i.e., not statistically significant). The decreased frequency of DR3 was only seen in patients with severe, long-standing disease. In contrast, the DRw6 increase was most pronounced in patients with severe disease (RR = 6.4; p = 0.003). There were no statistically significant deviations in the frequencies of DQ and DP alleles between patients and controls. In conclusion, our data suggest that DRW6 confers susceptibility and DR3 resistance to severe, long-standing disease.

Female↗
PubMed1990

Vitiligo is associated with HLA-DR4 in black patients. A preliminary report.

We have determined the HLA-DR and HLA-DQ phenotypes of 24 black patients with vitiligo and compared these with phenotypes of 143 local black controls. HLA-DR4 was significantly increased in patients, 38% vs 11% for controls. HLA-DQw3 was also increased in patients, 58% vs 32% for controls and may be explained in part by linkage disequilibrium with HLA-DR4. When patients were subgrouped according to family history of autoimmune disease and compared with controls, the increase in HLA-DR4 and HLA-DQw3 segregated with a positive family history. HLA-DRw6 in patients with a negative family history of autoimmune disease (64%) was significantly greater than the 10% in patients with a positive family history. When patients were subgrouped according to age at onset of disease, HLA-DR4 was increased in those with early onset of disease (younger than 20 years) while HLA-DRw6 was greater in patients who were older at onset of disease. These findings support the hypothesis of an immunogenetic influence on the expression of vitiligo in black patients with vitiligo.

Adolescent↗
PubMed1992

Twelve HLA-DR6-related DRB1 alleles and associated DR, DQ haplotypes in traditional Australians and other populations of Asia-Oceania.

The relative distributions of 12 HLA-DR6-related HLA-DRB1 alleles in indigenous populations of Australia, Melanesia, Polynesia, Micronesia, and northern and southern China have been determined by analysis of nucleotide sequence polymorphisms in 364 examples of HLA-DR6 positive chromosomes. Oligonucleotide hybridizations of polymerase chain reaction products of HLA-DQA1, DQB1, DRB1 and DRB3 genes generated 24 HLA-DR6-related haplotypes. The study aimed to determine the regional distribution of DR,DQ haplotypes associated with three novel HLA-DR6 alleles, namely DRB1*1408, 1409, and 1410, known to occur in Australian Aborigines, to gain further insights into the molecular phylogeny of these alleles. DRB1*1408 was the most common HLA-DR6 subtype in Oceania, although it was not detected in Chinese. In Australian Aborigines and Papua New Guinean highlanders, DRB1*1408 was associated with DRB3*0202, while in Polynesians and Micronesians it was associated with DRB3*0101. The different haplotype arrangements, together with the near absence of DRB1*1408 in coastal Melanesians, suggest the possibility that two independent mutations have generated DRB1*1408 in Australia and Oceania. DRB1*1409 and 1410 alleles were confined to Australian Aborigines, while DRB1*1407 was found exclusively in Melanesians; DRB1*1401 was the only HLA-DR6 allele represented in all study populations. The population-specific HLA-DR6 alleles and haplotypes have important implications for unrelated bone-marrow donor registries in Australia and Oceania.

Humans↗
PubMedDate not supplied

Possible association of juvenile myoclonic epilepsy with HLA-DRw6.

Juvenile myoclonic epilepsy (JME) is a clearly defined subform of idiopathic generalized epilepsy with a high aggregation of epilepsy in family members. With the HLA-system used as a genetic marker, a linkage between JME and the HLA region was demonstrated. Linkage with the HLA region suggests that JME may be associated with an HLA-antigen. An association could indicate that the gene lies in the HLA region and is in linkage disequilibrium with one of the HLA-antigens. Eighty-eight unrelated patients with JME were typed for the HLA-A and HLA-B locus, 77 were typed for the HLA-C locus, and 76 were typed for the DR locus. The antigen frequency was compared with those of healthy blood donors. The highest difference was noted in the frequency of DRw6 (39.5% in patients vs. 22.1% in controls). This weak association is open to question because DRw6 is known to split into DRw13 and DRw14.

Epilepsies, Myoclonic↗
PubMed1985

Polymorphisms within the HLA-DRw6 haplotype. II. Protein charge heterogeneity reflects MLC subtyping of HLA-DRw6 homozygous cells.

We have analyzed the HLA class II gene products from HLA-DRw6 homozygous cells. Epstein-Barr virus-transformed B-cell lines were internally labeled with [35S]-methionine. An NP-40 lysate of the cells was subjected to immunoprecipitation, first with a DRw52-like-specific monoclonal antibody and subsequently with a DR-specific framework antibody. The DR region-encoded gene products were analyzed by one-dimensional gel isoelectric focusing and two-dimensional gel electrophoresis. It is shown that DRw6 homozygous cell lines contain at least two nonallelic DR beta chains, one carrying a DRw52 determinant and one DRw52-negative population. Both chains appear to be polymorphic between the cellularly defined subtypes of DRw6. The determinant responsible for the differential mixed lymphocyte culture reactivity of Dw18 and Dw19 cells resides on the DRw52-positive population, whereas the Dw6-Dw9 differences are attributed to determinants on both populations of DR light chains. The Dw16-derived DRw52+ chain much resembles the Dw18 DRw52+ light chain whereas there is a clear-cut difference between these two subtypes in the DRw52- population. We conclude that, for DRw6 homozygous cells, the cellularly recognized D determinants are probably located on DR-encoded molecules, both DRw52+ and DRw52-, and that charge shift of these chains is at least partly responsible for differential recognition of these cells in mixed lymphocyte cultures.

Epitopes↗