摘要:

SUMMARYHLA‐DRB1, DQA1 and DQB1 alleles have been determined in 42 families with one IDDM proband and 64 healthy controls, by oligotyping (PCR‐SSO) using primers and probes from the XI International Histocompatibility Workshop. A positive DRB1 *03 and DRB1 *04 association with the disease was observed, whereas DRB 1*11 and DRB 1 *07 showed negative association but 19% of patients carried DRB1 alleles different to DRB 1 *03 or *04. When single alleles were considered, DQA1 *03 showed the strongest association with susceptibility to the disease (RR = 8.2, Pc = 0.00001) but this association was outgrown by 2 and 3 allele combinations, with genotype DRB 1 *04‐DQA 1 *03‐DQB1*0302/DRB1*03‐ DQA 1*0501‐ DQB 1*0201 showing the strongest association (RR = 28, Pc = 0.002). Application of the relative predispositional effect (RPE) method to our data, revealed a further susceptibility risk provided by the DRB1*13‐DQA1*0102‐DQB 1*0604 haplotype once DR3 and DR4 haplotypes were removed. When DQA1‐DQB1 genotypes were analysed for presence of Arg 52 (DQ α) and absence of Asp 57 (DQ β), genotypes SS/SS were found significantly increased in diabetics. Interestingly, one of the strongest associations with the disease was observed with the DQA 1*03‐DQB 1*0201 combination encoded mainly by genes in trans (RR = 11.7 Pc = 0.00004). These observations and their comparison with DR‐DQ haplotypes in more homogeneous ethnic groups support the stronger influence of theDQmolecule rather than the individual DR or DQ alleles in the susceptibility to IDDM. They also emphasize the need for detailed HLA haplotype studies in non‐Caucasian and ethnically mixed populations to gain further insight into the nature of genetic and environmental factors con

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00213.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYFactor B of human complement is encoded within the Major Histocompatibility Complex (MHC) and is polymorphic, with up to 30 alleles defined by electrophoretic mobility. One of the most common alleles, BF*F, is subdivided into the FA and FB subtypes, which differ at the gene level by non‐synonymous base substitutions in the seventh codon. We have found at this position a new restriction site polymorphism, as a Bsl I site absent from the FB allele. Using this restriction polymorphism, we have developed a method for BF F subtype determination, based on amplification by polymerase chain reaction of the 5’ end of the BF gene, and digestion with Bsl I. This new method has been applied to a panel of 29 selected BF F individuals. A single strand DNA conformation analysis of the same region of the gene allowed us to confirm the above DNA‐based BF F subtyping. During this study, two BF*F1 alleles showed discrepancies between protein and DNA typing, which were confirmed by our sequencing data. These were identical, in the 5’ region, to BF*S and BF*FB genes, respectively. In a comparison with two protein subtyping methods, identical results were found for only one third of the selected samples. The conflicting results may arise, in part, from previously undescribed molecular heterogeneity within BF F subtypes, or from the presence of a null allele. Our new method allows RF*F subtyping to be used with confidence in the definition of disease‐associated MHC h

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00214.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYSerological studies have demonstrated that lichen ruber planus is associated with the HLA‐DR1 antigen. This association was also confirmed by us in the Sardinian population. To establish which DRB1 molecular alleles are involved, we studied a selected group of 14 DR1 positive patients affected by cutaneous idiopathic lichen planus and a group of DR1 positive healthy controls using PCR with sequence‐specific primers (PCR‐SSP).Comparisons between the allele frequencies in patients and controls showed a positive association with cutaneous idiopathic lichen planus for the DRB 1*0101 allele (RR = 5.8,P= 0.0097). DRB1*0101 and DRB1*0102 are associated with the same DQA1 and DQB1 alleles and are different only for two amino acids in positions 85 and 86 of the DRB 1 gene. In our case report predisposition to cutaneous idiopathic lichen planus is correlated with a valine in position 85 and a glycine in position 86 at the second exon of the DRB 1

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00215.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYMany new Major Histocompatibility Complex (MHC) genes have been discovered in the last 5 years. Defining the polymorphism of these new genes may elucidate their function and their relevance to diseases with MHC associations. Polymerase chain reaction and single stranded conformation polymorphism (PCR SSCP) analyses were used to detect sequence polymorphisms of PERB1 demonstrated by comparing the available genomic sequence of four haplotypes. This study showed that PCR SSCP of PERB 1 is reproducible. In addition, PERB1 alleles segregate within families together with MHC haplotypes. Typing results from the Forth Asia and Oceania Histocompatibility Workshop (4AOHW) cell panel indicate that the identified polymorphisms of PERB 1 are ‘haplotypic’, i.e., unrelated individuals carrying the same MHC ancestral haplotypes carry the same PERB1 SSCP pattern. Interestingly, PERB1 SSCP patterns allow the distinction of ancestral haplotypes which share HLA‐B serological specificities, such as HLA‐B44 and therefore this analysis can be used to further define MHC haplotypes and thus to improve our understanding of the evolution of this

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00216.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYIn the study described here primers were designed forDQB1‘low‐resolution’, i.e. generic, typing by PCR amplification with sequence‐specific primers (PCR‐SSP) considering all the currently recognizedDQB 1alleles, i.e.0501‐0504.0601‐0609,0201,0301‐0305and0401‐0402.This resolution was achieved by performing eight PCR reactions per individual. TheDQB1alleles corresponding to the serological specificities DQ4, DQ5 and DQ6 were uniquely identified, whereas the DQ2. DQ7, DQS and DQ9 specificities were amplified by two primer mixes. All homozygous and heterozygous combinations of the serological series DQI to DQ9 could be distinguished. The yield of amplified products were increased compared to our previously describedDQB1‘high‐resolution’ typing technique by lengthening many of the primers, modifying the PCR cycling parameters and by including glycerol in the PCR reaction mixtures. Thirty‐one cell lines and 90 donor spleen cells were investigated by theDQB1‘low‐resolution’ PCR‐SSP technique as well as byTaq1 DRB‐DQA‐DQBRFLP analysis. The concordance between PCR‐SSP typing and RFLP analysis was 100%. The cell lines and 20 of the spleen cells were typed twice with complete reproducibility. No false positive or false negative typing results were obtained.DQB1‘low‐resolution’ PCR‐SSP typing, including DNA extraction, PCR amplification, gel detection, documentation and interpretation, were performed in 2 h which renders the PCR‐SSP technique suitable

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00217.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYTwenty‐eight cases of coeliac disease (CD) and seven of dermatitis herpetiformis (DH) have been verified in Iceland. Standard serological techniques were used for HLA typing. Twenty‐five individuals with CD were typed, 21 (84%) of whom carried DR3, DQ2. Twelve of these 25 (48%) had DR3, DR7, DQ2, which makes them possibly homozygous for DQ2, and suggests that homozygosity of DQ2 increases the risk for CD. The four DH patients that were typed all had HLA‐B8, DR3, DQ2. It is concluded that CD and DH are associated with DR3, DQZ in Icela

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00218.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYThe human TNF genes are located within the MHC class‐III region on chromosome 6. The presence or absence of an Nco‐I restriction site in the 5’ non‐coding sequence of the TNFβ gene defines two alleles (TNFB*1 and TNFB*2). The segregation of these alleles has been associated with levels of TNFα or TNFβ production in systemic lupus erythematosis (SLE), insulin‐dependent diabetes mellitus (IDDM) and in healthy control individuals.Rheumatoid arthritis (RA) is characterized by high levels of TNFα within the synovial fluid and to address the question of whether this could be brought about by a genetic predisposition to high TNF production by RA individuals, we examined the distribution of this Nco‐I polymorphism in 98 healthy volunteers and 123 patients with active rheumatoid arthritis. No difference was observed between the normal and RA groups with respect to haplotype segregation or allelic frequency. Furthermore, no difference was observed between DR4+or DR4‐individuals in the control or RA groups.These data demonstrate that the high level of TNFα seen in the joints of RA patients is unlikely to be due to a genetic predisposition of these patients to high TNFα production, as defined by the TNF Nco‐I restriction fragment lengt

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00219.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYSoluble HLA class I alloantigens (sHLA class I) can be typed according to their isoelectric points (IEP) after immunoprecipitation by w6/32 monoclonal antibody (mAb) coupled to immunomagnetic beads and focusing. In order to prove the large scale efficacy of this methodology, EDTA‐plasma samples from 344 probands HLA‐A, B typed by serology were analysed by one‐dimensional isoelectric focusing and HLA class I specific Westernblot (1D‐IEF). In addition, detergent solubilized HLA class I membrane molecules from approximately one half of the probands were studied too. Soluble HLA‐A24, B7, B18, B62 antigens were identified in nearly all experiments, whereas A28, B13, and B51 could be detected in about 50%. A third group of HLA antigens (A26, B8, B44) could be visualized rarely. The difficulties of detection might be due to the different affinity of mAb w6/32 to certain sHLA class I gene products or to variable amounts of sHLA class I in the plasma specimens. Some modifications of the antigen capture technique have already led to a slightly better degree of antigen recognition in 25 probands tested.Thus, HLA‐A, B typing using sHLA molecules and 1D‐IEF in the assay format presented does not yet seem to be a definitive alternative for HLA class I serology or biochemistry of membrane‐bound HLA class I molecules but it should be a promising technique if no cells are available or donor‐derived sHLA allotypes are to be monitored after HLA mismatched orga

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00220.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYIn order to identify new susceptibility markers for Rheumatoid Arthritis (RA), we analysed the dinucleotide repeat polymorphism at the T cell receptor delta locus (TCRD) in 65 RA patients and 99 healthy Belgian controls. A significant under‐representation of the A4‐A5 TCRD genotype was observed in the RA populat

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00221.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:1744-3121    

DOI:10.1111/j.1744-313X.1994.tb00222.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY