Wiley

The HLA‐associated susceptibility to develop celiac disease (CD) seems mainly to be conferred by a particular HLA‐DQ heterodimer encoded by the DQA1*0501 and DQB1*0201 genes either in cis or in trans position. To study the possible influence of DRB1 or other DQA1 and DQB1 alleles on the CD susceptibility conferred by these DQ genes, we performed genomic HLA typing of 94 CD patients, selected those who carried at least one copy of the DRB1*0301‐DQA1*0501‐DQB1*0201 haplotype (N = 89) and compared them to 47 random, healthy Norwegians matched with the patients to carry at least one copy of the above haplotype. We found an excess of DQB1*0201 homozygosity in the patients. This was due to an increased frequency of the DRB1*0301‐DQA1*0501‐DQB1*0201 and DRB1*0701‐DQA1*0201‐DQB1*0201 haplotypes present on the other chromosome. We propose that, in individuals carrying the DQA1*0501 and DQB1*0201 alleles, the presence of a second copy of the DQB1*0201 allele increases susceptibility to CD.

In this paper the first MHC data including HLA‐A, B, C, DR, DQ and complement BF, C4A, C4B determinants in German narcoleptics are presented together with the first family studies in European Caucasoids. 57 out of 58 unrelated patients (98.3%) were positive for DR2 and DQw1, respectively. In contrast to all other reports, one patient with typical signs of narcolelpsy was found to be DR2/DQw1 negative. Data showing significant increase in the frequency of B7, and normal frequencies of B35 were discordant with data from Japanese patients. Definition of the extended DR2 linked haplotypes, deduced from 6 families, revealed that 5 out of 12 were DQw1, DR2, BFS, C4B1, C4A3, B7 (Cw7), while 11/12 had DR2, DQw1, BFS, C4A3, C4B1 in common. In one multiple case family two genotypically different DR2 haplotypes were identified in affected siblings. Results from the family study were concordant with a dominant mode of inheritance with incomplete penetrance of a hypothetical disease susceptibility gene.

Abstract: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system with heterogeneous pathological features, disease courses and genetical backgrounds. In this study we determined whether genetic variants of toll‐like receptor (TLR) 4, which confer substantial differences in the inflammation elicited by bacterial lipopolysaccharide, are related to the development of MS. We found no differences in the frequencies of the cosegregating TLR4 Asp299Gly and Thr399Ile polymorphisms between Austrian MS patients (11.6%) and age‐matched controls (13.7%). Furthermore, we could not detect any influence of these mutations on clinical parameters and serum levels of soluble adhesion molecules of MS patients. Our data indicate that these TLR4 polymorphisms have no influence on the incidence, progression and inflammatory parameters of MS.

Abstract: Multiple sclerosis (MS) has, since the 1970s, been known to be associated with the HLA‐Dw2 and ‐DR2 specificities in Caucasian Europeans and North Americans. By the use of genomic typing techniques, the association has been specified to be with the DRwlS,DQw6,Dw2, i.e. the DRBI* 1501‐DQAI*0102‐DQBl*0602 haplotype. A significant DPw4 association in Scandinavian MS patients has been described in one report. However, this association has not been confirmed in several subsequent studies with patients from the same and other ethnic groups. During the last few years several reports, based on serological, RFLP and PCR‐SSO data, have suggested that the HLA class II‐associated MS susceptibility gene(s) may be more closely associated with the DQ than with the DR subregion. The observations that the HLA‐DQBI genes of MS patients share long stretches of sequence motifs and also carry DQA1 alleles encoding glutamine at position 34 of the DQ α chain have received considerable attention. It has been suggested that the susceptibility to develop MS might be determined by the corresponding DQ α‐β heterodimers either encoded in cis or in trans. We have investigated these issues in a large group of Swedish MS patients (n= 179). We found that the associations with the suggested DQBI sequences and position 34 of the DQ α chain were due to linkage disequilibrium and secondary to the association with the DRw15,DQw6,Dw2 haplotype (p < 10‐⁹ and p < 10‐⁸, respectively). No overrepresentation of the implicated DQ α‐β heterodimers was observed in DRw1S,DQw6,Dw2‐negative patients. We conclude that available data does not allow the localization of the HLA class II‐associated MS susceptibility genes within the DRw15,DQw6,I>w2 haplotype. We have previously described immunogenetic differences between different clinical forms of MS. In the present study of a new group of MS patients compared with a new control panel, these differences were partly confirmed. The DRw17,DQw2 association in relapsing/remitting MS was affirmed. However, in patients with primarily chronic progressive MS a negative association with the DQw7 allele was not substantiated and a positive association with the DR4.DQw8 haplotype could neither be confirmed nor rejected.

Abstract: Behçet’s disease (BD) is known to be associated with human leukocyte antigen (HLA) B51 in many different ethnic groups. An increased incidence of HLA‐B51 in the patient group has also been reported in a Japanese population. Recently, the B51 antigen has been identified to comprise 21 alleles, B*5101–B*5121. Further, not only HLA‐B*5101 but also HLA‐B*5108 were found to be relatively increased in the patient groups among Italian and Saudi Arabian populations. Therefore, we performed HLA‐B*51 allele genotyping by the polymerase chain reaction‐sequencing based typing (PCR‐SBT) method in order to investigate whether there is any correlation of one particular B51‐associated allele with Japanese BD. Ninety‐six Japanese patients with BD and 132 healthy Japanese volunteers were enrolled in this study. As a result, the phenotype frequency of the B51 antigen was confirmed to be remarkably increased in the patient group as compared to the ethnically matched control group (59.4% in patients vs. 13.6% in controls; Pc=0.0000000000098, R.R.=9.3). In the B*51 allele genotyping, 56 out of 57 B51‐positive patients were defined as B*5101 and the remaining one was B*5102. In contrast, all of 18 B51‐positive normal controls were B*5101. None of the Japanese patients and healthy controls carried the HLA‐B*5108 allele. This study revealed that B*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of the HLA‐B51 antigen in the Japanese BD patient group was mostly caused by the significant increase of the HLA‐B*5101 allele.

We have updated the catalogue of common and well‐documented (CWD) human leukocyte antigen (HLA) alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, and ‐DPB1 loci in IMGT (IMmunoGeneTics)/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1 and ‐DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being ‘common’ (having known frequencies) and 707 as being ‘well‐documented’ on the basis of ~140,000 sequence‐based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program's bioinformatics web pages.

Abstract: The characteristics of canine homologues of CD4 and CD8, defined by murine monoclonal antibodies CA13.1E4 (IgG1) and CA9.JD3 (IgG2a) respectively, are described. These antibodies identify mutually exclusive subpopulations of non‐B lymphocytes in peripheral lymphoid organs and blood. However, in thymus the antibodies defined populations of double‐positive, double‐negative and single‐positive cells that showed a progressive maturation consistent with that described for CD4 and CD8 in other mammalian species. Furthermore, functional studies clearly associated cytotoxic effector cell function with the subpopulation reactive with CA9.JD3 (CD8). In contrast, proliferation stimulated by allogeneic cells and mitogens was more pronounced in the subpopulation reactive with CA13.1E4 (CD4). Cell and tissue distribution studies revealed that CA13.1E4 stained neutrophils with equivalent intensity to the staining of peripheral T cells. CA13.1E4 precipitated a 60 kD protein from the surface of T cells and highly purified neutrophils under both reducing and non‐reducing conditions. CA9.JD3 precipitated a heterodimer of 32 kd and 36 kD under reducing conditions, and a 70 kD protein under non‐reducing conditions. The expression of CD4 by canine neutrophils is without precedent in other mammalian species; the functional significance of neutrophil CD4 expression is puzzling in light of the current understanding of the functions of CD4 which include it's role as a receptor for non‐polymorphic regions of MHC class II molecules.

Blood groups and HL‐A antigens were determined in 12 members of a family in which chronic lymphocytic leukaemia (CLL) occurs in four siblings. The same HL‐A haplotype [Da25 (W30 + W31), HL‐A13] was observed in the three diseased siblings tested.

This case, together with that of a similar family studied by Schweitzer et al. (1973), in which three out of five diseased siblings shared two antigens ‐ HL‐A2 and W5 ‐ suggests a possible linkage between HL‐A and susceptibility to CLL.