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Results for “HLA-DR7 Antigen”

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At least 19 recordsLinked to original sources
PubMed1992

HLA haplotype segregation and ultrastructural study in familial immotile-cilia syndrome.

The immotile-cilia syndrome (ICS) is a congenital disorder characterized by dysmotility or even complete immotility of the cilia in the ciliated epithelia. The most frequent consequences include recurrent airway infections from early childhood. Neonatal asphyxia often occurs. Males are usually sterile, whereas females may be fertile or infertile. The disease is inherited as an autosomal recessive trait, but previous attempts to localize the ICS susceptibility gene have so far been unsuccessful. Here, we present the case of two sib pairs affected by ICS from two unrelated families. The electron microscopic investigation of nasal biopsies showed structural anomalies of the cilia, characterized by single microtubules or doublets, arranged randomly in the axoneme. Histocompatibility antigen (HLA)-genotyping of all family members revealed: 1) a significant association of ICS with the HLA-DR7; DQW2 haplotype, which is shared by all the affected sibs (P = 0.0099; RR = 25.94); 2) a possible linkage of the ICS susceptibility gene with HLA, both the affected sibs being HLA-identical, the healthy brother in family B being HLA-different (sib-pair analysis: P less than 0.001).

Child, Preschool↗
PubMed1992

HLA antigens and intracranial aneurysms.

The frequencies of the HLA-A, -B and -DR were determined in a group of 59 transplant donors who died from subarachnoid haemorrhage within three days following the rupture of intracranial aneurysm (the SAH group) and compared with those of a control group consisting of 389 donors who died from other causes. The only significant difference was in the increased frequency in the SAH group of non-typed ("empty")-DR loci in association with the DR7 phenotype. The most probable explanation of this finding is that in the SAH group the frequency of DR7 homozygotes is several times higher than in the general population, and that bearing the DR7 allele in homozygotic form is associated with a very high risk of developing potentially fatal intracranial aneurysmal haemorrhage.

Autoimmune Diseases↗
PubMed1992

The preexcitation syndrome: epidemiological and genetic study.

A sample of 4210 subjects of both sexes aged 35-54 years was examined, chosen at random from six regions of Croatia. An electrocardiogram at rest was performed in all subjects and changes analyzed by the Minnesota code. A short P-R interval together with a widening QRS complex and a delta wave was found in 0.05%, while 42 (1.0%) of the examinees had a short P-R interval, but only 0.21% were symptomatic. Three years after the first examination 0.06% of the subjects had preexcitation with a delta wave, and in one subject it appeared after three years. 0.35% of the subjects had a short P-R interval after three years but only 0.18% were symptomatic and in 22 (0.65%) it had disappeared in three years. After 13 years these subjects did not appear for an examination, and the short P-R interval did not appear in any of other subjects during this period. There were more short P-R intervals: 3.22% in females and 1.96% in males, but 0.33% only were symptomatic. Antigens of the human leukocyte group A (HLA) system were analyzed in 46 patients: the Wolff-Parkinson-White syndrome was found in 35, while 11 had the Lown-Ganong-Levine syndrome. Antigens of the HLA-A, HLA-B and HLA-DR locuses were determined by the microlymphocytotoxicity method. The results of the frequency of HLA system antigens were compared to the results of the control group of a Croatian population consisting of 175 people. There was an increased frequency of HLA-A9 and HLA-B5 (P = 0.026 and 0.0092) in the investigated population as a whole. The participation of HLA-A3 antigen was significantly less among patients (P = 0.03), while HLA-B14 antigen was not found in patients with preexcitation. Within 10 HLA-DR locuses, HLA-DR7 antigen was rather more frequently present, although this was not statistically significant (P = 0.173).

Adult↗
PubMed1992

HLA class II alleles associated with celiac disease susceptibility in a southern European population.

Susceptibility to celiac disease in Northern Europe is associated with the human leukocyte antigens (HLA) B8, DR3 and DQ2, which exist together on an extended haplotype. The strong predominance of this haplotype within the Northern European celiac populations, together with the linkage disequilibrium which occurs between these loci, does not allow identification of the gene(s) primarily associated with disease susceptibility. Studies from Southern Europe using both serology and examination of restriction fragment length polymorphisms (RFLP) have demonstrated associations with DR3, DR7 and DQ2, suggesting that the DQ locus is primarily involved. We investigated 43 celiac patients and 41 healthy controls from Rome, Italy, using sequence-specific oligonucleotide (SSO) probes, in conjunction with gene amplification by the polymerase chain reaction (PCR), to determine alleles at the DRB, DQA1, DQB1 and DPB1 loci: 19% of celiac patients possessed the alleles DRB1*0301 DRB3*0101, 33% DRB1*0301 DRB3*0201 and 33% of celiac patients were heterozygous for DRB1*1101-1201/DRB1*0701. The strongest association with celiac disease susceptibility was the combination of alleles DQA1*0501 DQB1*0201 (91% celiac patients vs. 12% controls; p = 0.000002). There was no additional susceptibility associated with alleles at the DPB locus. This study confirms the hypothesis that susceptibility is associated with a particular combination of DQ alleles and the ethnic variation in DR frequencies is secondary to linkage disequilibrium with these DQ alleles.

Adolescent↗
PubMed1992

Skin cancers and HLA frequencies in renal transplant recipients.

An association between HLA DR7 and the development of multiple non-melanoma skin cancer was detected in immunosuppressed patients in southern Australia. The relative risk was 2.6 which was lower than for immunocompetent patients with the same skin cancers. HLA frequencies of renal transplant recipients with multiple skin cancers were determined. The types HLA B27 and HLA Dr7 were found in significantly higher frequency, and there was no absence of HLA A11.

Adult↗
PubMed1992

Identification of the recombination site within the steroid 21-hydroxylase gene (CYP21) of the HLA-B47,DR7 haplotype.

The HLA haplotype A3-Cw6-B47-C4A91-BQ0-DR7 is associated with congenital adrenal hyperplasia (CAH), since it only carries the dysfunctional steroid 21-hydroxylase A pseudogene as well as the 5' adjacent complement C4A gene. The recombination site leading to the deletion of the complement C4B and steroid 21-hydroxylase B genes in this haplotype was studied by determining the 21-hydroxylase genomic DNA sequence in comparison to the standard CYP21A- and CYP21B-specific sequences. A 200-bp region between exons 7 and 8 was identified as a possible recombination site. Thus the deleted area comprises the 3' end of the CYP21A pseudogene, the entire C4B gene and the 5' end of the CYP21B gene. The findings were confirmed by PCR amplification of a 1.8-kb fragment of the CYP21 gene. This PCR system is specific for CYP21A/B recombinant genes and may be used for screening among CAH patients carrying this type of deletion.

Adrenal Hyperplasia, Congenital↗
PubMedDate not supplied

Anticardiolipin antibodies in a patient with Crohn's disease and thrombosis.

Thrombosis is an uncommon though well recognized complication of inflammatory bowel disease, for which various coagulation alterations have been described as possible causes. Antiphospholipid syndrome (APS) is defined as the association of thrombosis, fetal loss and thrombocytopenia with anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). We describe a case of a 21-year-old female with recurrent thrombosis associated with aCL who went on to develop Crohn's disease. Tissue typing done in this patient revealed the presence of the HLA-DR7, DRw53, which previous studies have shown to be found in increased frequencies in APS patients. To our knowledge, this is the first report of an association between these two clinical conditions and, in this particular case, aCL may be implicated in the thrombotic events.

Adult↗
PubMed1992

Specificity and T cell receptor beta chain usage of a human collagen type II-reactive T cell clone derived from a healthy individual.

Collagen type II (CII) is a cartilage-specific matrix compound well known as an inducer of an experimental, T cell-dependent autoimmune arthritis, a disease which shows some similarities to human rheumatoid arthritis. Here we report on an HLA-DR7-restricted human CD4 T cell clone (TC9), which was isolated from a healthy donor and recognizes human CII. After screening CNBr fragments of CII and tryptic fragments derived thereof, the T cell epitope could be mapped to amino acid residues 271-285 of the triple helical region of CII that are located within CNBr fragment 11 [alpha 1 (II) CB11]. This epitope was confirmed by a synthetic peptide stimulatory for TC9. The T cell receptor beta chain of TC9 was cloned using the polymerase chain reaction; it comprises V beta 6.7 and contains besides J beta 2.3 and C beta 2 an as yet undescribed sequence for the D segment.

Adult↗
PubMed1991

Analysis of HLA-DRB and -DQB gene RFLPs in DR7 homozygous cell lines: associations with Dw11, Dw17 and DB1.

The DR7-associated Dw specificities, Dw11, Dw17 and DB1 were investigated with regard to DRB- and DQB-gene polymorphism, as revealed by RFLP analysis using the restriction enzyme TaqI. In the 22 DR7 homozygous cell lines investigated, each of these Dw specificities was found to correlate to one specific RFLP defined DR-DQ haplotype. In addition, a clear linkage disequilibrium to a specific HLA-B locus allele for each Dw specificity was noted, indicating that the Dw subtypes of DR7 often are associated with a conserved HLA-B-DR-DQ haplotype. Only one genetically homozygous cell line, PLH, deviated from these correlations. This cell line, notably derived from an individual with a deletion of the 21-hydroxylase B-gene (21-OHB), caries the HLA haplotype Bw47, DR7, DQw2, DB1, but displayed a DRB RFLP otherwise found in association with Dw17.

Cell Line↗
PubMed1992

Is persistent polyclonal B lymphocytosis caused by Epstein-Barr virus? A study with polymerase chain reaction and in situ hybridization.

Previous reports of patients with persistent polyclonal B lymphocytosis have found associations with female sex, cigarette smoking, HLA-DR7 phenotype, and moderate elevation of peripheral blood polyclonal B lymphocytes. The presence of binucleated cells and atypical lymphocytes in the peripheral blood of these patients was highly suggestive of a viral infection, such as with the Epstein-Barr virus. We report a 47-year-old asymptomatic woman who was incidentally found to have persistent polyclonal B lymphocytosis and serum IgG against virus capsid antigen (VCA) and Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) of EBV. The presence of EBV was investigated in the peripheral blood lymphocytes from this patient by in situ hybridization and polymerase chain reaction methods. EBV DNA was demonstrated in the lymphocyte fraction by polymerase chain reaction, and it was further located in lymphoid cells by in situ hybridization. These results indicate that persistent polyclonal B lymphocytosis is strongly associated with EBV.

B-Lymphocytes↗
PubMed1991

Role of the adhesion molecule ICAM-1 (CD54) in staphylococcal enterotoxin-mediated cytotoxicity.

Staphylococcal enterotoxin A (SEA) binds to major histocompatibility complex (MHC) class II molecules on target cells and directs human cytotoxic T lymphocytes (CTL) of irrelevant nominal specificity to mediate strong cytotoxicity against target cells. In this report we describe the importance of ICAM-1 (CD54) expression on the target cell in SEA-dependent cell-mediated cytotoxicity (SDCC), utilizing murine L cells co-transfected with HLA-DR and ICAM-1. Human CTL mediated a low but significant cytotoxicity against HLA-DR2- and HLA-DR7-transfected cells after preincubation with SEA, but no reactivity towards uncoated HLA-DR2 and HLA-DR7 cells or SEA-coated ICAM-1-transfected and untransfected L cells. In contrast, a strong cytotoxic response was mediated by CTL against L cells co-transfected with HLA-DR2/ICAM-1 and HLA-DR7/ICAM-1. Similar cytotoxic activity of the CTL was seen at a 30-fold lower effector-to-target cell ratio when comparing the HLA-DR2/ICAM-1-expressing cells with the HLA-DR2-expressing cells. SEA dose-response analysis demonstrated that the HLA-DR2/ICAM-1-expressing target cells enabled the CTL to respond to a 1000-fold lower concentration of SEA in comparison to the HLA-DR2-expressing cells. CD3+CD4+ and CD3+CD8+ cytotoxic T cell lines were equally dependent on the expression of ICAM-1 on the target cell. The strong CTL activity against HLA-DR2/ICAM-1-transfected cells could be blocked by anti-CD11a or anti-CD18 monoclonal antibodies (mAb), but not by anti-CD11b, anti-CD11c, anti-CD2 or unrelated control mAb. The great sensitivity of HLA-DR2/ICAM-1 expressing target cells to SDCC was strongly reduced by preincubation with various anti-ICAM-1 mAb but not by mAb against monomorphic HLA-DR or murine MHC class I determinants. The result in this study clearly demonstrates that efficient re-targeting of human CTL by SE is dependent on a proper interaction with the heterodimer CD11a/CD18 (Leu-CAMa, LFA-1) on the CTL and its target cell ligand ICAM-1.

Antibodies, Monoclonal↗
PubMed1992

Mhc-DRB diversity of the chimpanzee (Pan troglodytes).

Fifty-four chimpanzee Patr-DRB and five human HLA-DRB second exons were cloned and sequenced from thirty-five chimpanzees and four human B-cell lines and compared with known Mhc-DRB sequences of these two species. Equivalents of the HLA-DRB1*02, -DRB1*03, -DRB1*07 allelic lineages and the HLA-DRB3, -DRB4, -DRB5, -DRB6, and -DRB7 loci were all found in the chimpanzee. In addition, two chimpanzee Patr-DRB lineages (Patr-DRBX and -DRBY) were found for which no human counterparts have been described. None of the Patr-DRB sequences is identical to known HLA-DRB sequences. The Patr-DRB1*0702 and HLA-DRB1*0701 alleles are the most similar sequences in a comparison between the two species and differ by only two nucleotides out of 246 sequenced. Equivalents of the HLA-DRB1*01, -DRB1*04, and -DRB1*09 alleles were not found in our sample of chimpanzees. A per locus comparison of the number of Patr-DRB alleles with the HLA-DRB alleles shows that the Patr-DRB3, -DRB4, -DRB5, and -DRB6 locus are, thus far, more polymorphic than their human homologs. The polymorphism of the Patr-DRB1 locus seems to be less extensive than that reported for the HLA-DRB1 locus. Nevertheless, the Patr-DRB1 locus seems to be the most polymorphic of the Patr-DRB loci. Phylogenetic analyses indicate that the HLA-DRB1*09 allele may have originated from a recombination between a Mhc-DRB5 allele and the DRB1 allele of a Mhc-DR7 haplotype. Although recombination seems to increase the diversity of the Patr-DRB alleles, its contribution to the generation of Patr-DRB variation is probably low. Hence, most Patr-DRB diversity presumably accumulated via recurrent point mutations. Finally, two distinct Patr-DRB haplotypes are deduced, one of which (the chimpanzee equivalent of the HLA-DR7 haplotype) is probably older than 6-8 million years.

Amino Acid Sequence↗
PubMed1991

A family study confirms that the HLA-DP associations with celiac disease are the result of an extended HLA-DR3 haplotype.

Genotyping for HLA-DR, -DQ, and -DP antigens by restriction fragment length polymorphism (RFLP) analysis along with identification of restriction fragments associated with celiac disease (CD) were undertaken in 13 families in which more than one member had CD. Major histocompatibility complex class II haplotypes for the family members were constructed which included both genotypes and RFLP markers. In 12 of the families all the affected members shared an HLA haplotype which included HLA-DR3a, DQw2 and a BglII 4.0-kb DQA fragment. Eight of these 12 haplotypes also included HLA-DPw1 and both a RsaI 4.0-kb DPB fragment and an XbaI 16.0-kb DPA fragment. In one family, the two affected members shared an HLA-DR7, DQw2 haplotype, although both their second haplotypes included HLA-DR3a and -DQw2. The results suggest that HLA-DP genes do not play an independent predisposing role in the etiology of CD but do mark a disease-associated extended haplotype. This haplotype contains genes coding for specific HLA products which may be necessary for the disease to develop. The findings support the hypothesis that the presence of a specific DQ alpha/DQ beta heterodimer, encoded in a cis arrangement on HLA-DR3a haplotypes, predisposes to celiac disease.

Adolescent↗
PubMed1992

The influence of HLA A-B-DR matching on cytomegalovirus disease after renal transplantation. Evidence that HLA-DR7-matched recipients are more susceptible to cytomegalovirus disease.

We examined the prevalence of cytomegalovirus infectious episodes, as defined by clinical, virological, and serological criteria (i.e., CMV disease), in 660 kidney graft recipients; 109 patients (16.5%) developed the disease, and 551 did not. No significant statistical link between CMV disease prevalence and a given HLA-A, -B, or -DR allele was observed. However, patients with HLA-DR7 matched grafts were statistically more frequently found (P < 0.01) in the group of recipients who developed CMV disease as compared with the group who did not develop CMV disease. Furthermore, among patients who developed CMV disease, a significant increase of HLA-DR7 matched over DR7 mismatched patients was noted, whereas no difference between matched and mismatched recipients for the other HLA-DR alleles was found. No difference in the severity of graft failure, often observed during, or immediately after, the CMV episode, was noted between patients matched or mismatched for HLA-DR7. Our data suggest that donor/recipient matching for HLA-DR7 is associated with increased CMV disease.

Alleles↗
PubMed1992

Structural similarity of the HLA-DQ region in DQ3 and DQ4 haplotypes and structural diversity of the HLA-DQ region in HLA-DR7 haplotypes.

Genomic DNA obtained from a B lymphoblastoid cell line was digested with appropriate restriction endonuclease and hybridized with several probes specific for genes encoding HLA-DQ. Southern hybridization with a DQA1 3'untranslated (UT) region probe showed DQ2-type hybridization pattern in DR7DQ3 haplotype. On the contrary, DQB1 3'UT probe showed DQ3-type pattern in the same haplotype. Gene cloning and DNA sequencing analysis revealed a repetitive sequence, (TG)19, between DQA1 and DQB1 gene in the DR7DQ3 haplotype. These results suggest that a recombination event has occurred near this potential Z-DNA structure in the haplotype, DR7DQ3. The 3'UT region probes of DQA1 and DQB1 genes failed to detect restriction fragment length polymorphism (RFLP) differences between DR4DQ3 and DR4DQ4 haplotypes in this experiment, suggesting that the gene structure between DQA1 and DQB1 is conserved in these haplotypes.

Antigenic Variation↗