Background. Severe aplastic anemia (SAA) is defined as pancytopenia caused by bone marrow failure. The pathogenesis of SAA is thought to involve autoimmune processes. Increased susceptibility to autoimmunity has been shown to be associated with several different HLA alleles. in SAA, few large studies based on data mainly from adults describe a positive HLA correlation with HLA-DR2 (DRB1*15) and HLA-B14. Procedure. This study explored the HLA constitution of 181 children with SAA who were enrolled in the prospective multi-center study SAA94 between January 1994 and January 2002. The control group consisted of 303 healthy individuals of comparable demographic background. Allelic frequencies between patients and controls are compared using Fisher's exact test. Results. In our pediatric cohort, we describe a positive association with HLA-B1 4 (P=0.0039), but no association of HLA-DR2 with SAA. Conclusion. HLA associations appear to be different in children and adults with SAA. This might point towards a difference in pathophysiology between at least part of the children and adults.

Routine typing of a potential bone marrow donor by sequence-specific oligonucleotide probes (SSOP) and sequence based typing (SBT) produced inconclusive subtyping results, suggesting a new allele. A magnetic bead-based method, haplotype specific extraction (HSE), was used to separate the diploid sample into its haploid components. The sample was then re-typed using standard SBT, revealing a new human leukocyte antigen (HLA) allele, since named B*1576. HSE used in conjunction with standard SBT is a convenient and simple tool for resolving ambiguous and novel allele combinations without the need for amplification or subcloning.

BACKGROUND:Mycophenolate mofetil (MMF) is a routinely used immunosuppressive agent that selectively blocks T- and B-lymphocyte proliferation. The present study was designed to investigate the effects of this drug on human leukocyte(HLA) antibody production in general and donor-specific antibody (DSA) formation in particular in 154 recipients of renal allografts.PATIENTS AND METHODS:Renal allograft recipients were subdivided into three groups. Group 1 patients (n = 60) had received MMF since transplantation in combination with either cyclosporin A or tacrolimus and steroids. Group 2 patients (n = 29) had received an MMF-free immunosuppressive regimen initially followed by addition of MMF some time later. Group 3 patients (n = 65) had received no MMF. Cyclosporin A or tacrolimus in combination with azathioprine and/or steroids were used for immunosuppression. DSA were demonstrated by enzyme-linked immunosorbent assay (ELISA) for detection of panel-reactive antibodies of HLA class I and II specificity.RESULTS:The HLA antibodies were found in 16.7%, 27.6% and 30.8% of transplant recipients in groups 1, 2 and 3, respectively. DSA were found in 8.3%, 17.2% and 20.0%, and non-DSA in 10.0%, 20.7% and 24.6%, of patients in groups 1, 2 and 3, respectively.CONCLUSION:The MMF reduces anti-HLA class I and II antibody production and consequently DSA production in renal allograft recipients. Our data indicate this effect to be more pronounced in patients given MMF immediately after transplantation than in those in whom MMF is introduced some time later. The presence of DSA in the serum of renal allograft recipients is associated with poorer graft function (higher serum creatinine and more rejection episodes).

PURPOSE:In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined. PATIENTS AND METHODS:Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene. Statistical analysis was performed using the chi2 test and the Fisher's exact test, respectively. RESULTS:The homozygous genotype IL-1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer (P < .0001), whereas further associations with the IL-1 gene cluster were not observed. A weak association of the TNF-A-308A allele with the diffuse type of early-stage gastric cancer, and an association with a composite of two or three proinflammatory polymorphisms, which predispose to increased production of the proinflammatory cytokines IL-1beta and TNF-alpha, could also be demonstrated. CONCLUSION:The genotype IL-1RN*2/2 seems to be associated with early-stage gastric cancer. As opposed to advanced-stage gastric cancer, further proinflammatory cytokine polymorphisms were not associated independently, but might act in combination and mirror early steps of gastric carcinogenesis in hosts colonized by Helicobacter pylori. However, these findings await confirmation in future trials and should be underscored by gene expression studies.

Three different Venezuelan Amerindian tribes were studied for human leukocyte antigen (HLA)-DPA1 and DPB1 allelic variability using polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and sequence-based typing in a selected group of samples. These tribes are geographically (two from the Perija Mountain range and one from the Orinoco Delta) and linguistically distinct: the Bari (from Campo Rosario and Saymaidoyi villages) and the Warao have been classified within the Chibcha linguistic family, whereas the Yucpa (from the Aroy, Marewa, and Peraya villages) are Carib speaking. Venezuelan Indians, like other Native American tribes, show a markedly reduced number of different HLA-DP alleles (range, 2-7) and haplotypes (range, 4-11) in comparison with neighboring Venezuelan mestizo and other non-Indian populations. Some HLA-DPB1 (*0402 and *1401) alleles characteristic for all Amerindian tribes are present also in these populations. Despite general similarities, each tribe and, in some cases, some subtribes show their own pattern of allele and haplotype distribution apparently more as a result of linguistic than to geographic variation.

Arthritis & RheumatismVolume 42, Issue 7 p. 1552-1553 Concise CommunicationFree to Read An update on HLA association of Mi-2 autoantibodies: The association with a tryptophan at position 9 of the HLA–DRβ chain is strong but not absolute Rudolf Mierau PhD, Rudolf Mierau PhD Research Institute, and Clinic of Rheumatic Diseases, Aachen, GermanySearch for more papers by this authorThomas Dick PhD, Thomas Dick PhD Research Institute, and Clinic of Rheumatic Diseases, Aachen, GermanySearch for more papers by this authorPeter Bartz-Bazzanella MD, Peter Bartz-Bazzanella MD Kreiskrankenhaus Würselen, Würselen, GermanySearch for more papers by this authorElisabeth Keller PhD, Elisabeth Keller PhD Laboratory for Immunogenetics, Munich, GermanySearch for more papers by this authorEkkehard D. Albert MD, Ekkehard D. Albert MD Laboratory for Immunogenetics, Munich, GermanySearch for more papers by this authorEkkehard Genth MD, Ekkehard Genth MD Research Institute, and Clinic of Rheumatic Diseases, Aachen, GermanySearch for more papers by this author Rudolf Mierau PhD, Rudolf Mierau PhD Research Institute, and Clinic of Rheumatic Diseases, Aachen, GermanySearch for more papers by this authorThomas Dick PhD, Thomas Dick PhD Research Institute, and Clinic of Rheumatic Diseases, Aachen, GermanySearch for more papers by this authorPeter Bartz-Bazzanella MD, Peter Bartz-Bazzanella MD Kreiskrankenhaus Würselen, Würselen, GermanySearch for more papers by this authorElisabeth Keller PhD, Elisabeth Keller PhD Laboratory for Immunogenetics, Munich, GermanySearch for more papers by this authorEkkehard D. Albert MD, Ekkehard D. Albert MD Laboratory for Immunogenetics, Munich, GermanySearch for more papers by this authorEkkehard Genth MD, Ekkehard Genth MD Research Institute, and Clinic of Rheumatic Diseases, Aachen, GermanySearch for more papers by this author First published: 26 April 2001 https://doi.org/10.1002/1529-0131(199907)42:7<1552::AID-ANR33>3.0.CO;2-KCitations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES 1 Targoff IN, Reichlin M. The association between Mi-2 antibodies and dermatomyositis. Arthritis Rheum 1985; 28: 796–803. 10.1002/art.1780280711 CASPubMedWeb of Science®Google Scholar 2 Aubry F, Mattei MG, Galibert F. Identification of a human 17p-located cDNA encoding a protein of the Snf2-like helicase family. Eur J Biochem 1998; 254: 558–64. 10.1046/j.1432-1327.1998.2540558.x CASPubMedWeb of Science®Google Scholar 3 Seelig HP, Moosbrugger I, Ehrfeld H, Fink T, Renz M, Genth E. The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum 1995; 38: 1389–99. 10.1002/art.1780381006 CASPubMedWeb of Science®Google Scholar 4 Ge Q, Nilasena DS, O'Brien CA, Frank MB, Targoff IN. Molecular analysis of a major antigenic region of the 240-kd protein of Mi-2 autoantigen. J Clin Invest 1995; 96: 1730–7. 10.1172/JCI118218 CASPubMedWeb of Science®Google Scholar 5 Seelig HP, Renz M, Targoff IN, Ge Q, Frank MB. Two forms of the major antigenic protein of the dermatomyositis-specific Mi-2 autoantigen [letter]. Arthritis Rheum 1996; 39: 1769–71. 10.1002/art.1780391029 CASPubMedWeb of Science®Google Scholar 6 Mierau R, Dick T, Bartz-Bazzanella P, Keller E, Albert ED, Genth E. Strong association of dermatomyositis-specific Mi-2 autoantibodies with a tryptophan at position 9 of the HLA-DRβ chain. Arthritis Rheum 1996; 39: 868–76. 10.1002/art.1780390521 CASPubMedWeb of Science®Google Scholar 7 Nevinny-Stickel C, Hinzpeter M, Andreas A, Albert ED. Nonradioactive oligotyping for HLA-DR1-DR10 using polymerase chain reaction, digoxigenin-labeled oligonucleotides and chemiluminescent detection. Eur J Immunogenet 1991; 18: 323–32. 10.1111/j.1744-313X.1991.tb00032.x CASPubMedWeb of Science®Google Scholar 8 Keller E, Zhu Y, Volgger A, Lang B, Albert ED. A novel variant of DR4 (DRB1*0421) identified in a patient with polychondritis. Immunogenetics 1995; 41: 171. 10.1007/BF00182335 CASPubMedWeb of Science®Google Scholar 9 Scharf SJ, Long CM, Erlich HA. Sequence analysis of the HLA-DR and HLA-DQ loci from three pemphigus vulgaris patients. Hum Immunol 1988; 22: 61–9. 10.1016/0198-8859(88)90052-3 CASPubMedWeb of Science®Google Scholar 10 Olerup O, Zetterquist H. HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 1992; 39: 225–35. 10.1111/j.1399-0039.1992.tb01940.x CASPubMedWeb of Science®Google Scholar 11 Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas MC, Plotz PH, et al. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 1991; 70: 360–74. 10.1097/00005792-199111000-00002 CASPubMedWeb of Science®Google Scholar Citing Literature Volume42, Issue7July 1999Pages 1552-1553 ReferencesRelatedInformation

Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. No elevation in the frequency of any HLA class II alleles was observed in GDM patients compared to 254 non-diabetic unrelated subjects. DR3 allele frequency was significantly increased in 43 women with islet autoantibodies [corrected P value (P-c) = 0.02], in particular in those with GADA (P-c = 0.002), or in the 24 women who developed IDDM postpartum (P-c = 0.005). In women with GADA, DR4 and DQB1*0302 were significantly elevated (P-c = 0.009). Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. These results indicate that women with GDM who have islet autoantibodies at delivery or develop IDDM postpartum have HLA alleles typical of late-onset type 1 diabetes, and that both HLA typing and islet antibodies can predict the development of postpartum IDDM.

Juvenile arthritis (JA) is a term that covers a number of different disease entities, of which only three present with significant Human Leukocyte Antigen (HLA) associations. (1) Pauciarticular JA with late onset and a strong male proponderance is associated with HLA-B27 and represents the group of juvenile spondyloarthropathies related to adult ankylosing spondylitis. (2) Early onset pauciarticular JA with a preponderance of females and a frequent occurance of chronic iridocyclitis and the frequent presence of anti-nuclear antibodies is associated with alleles from three different regions of the HLA system: HLA-A2 , which shows a very strong correlation with early age of onset; DR8, DR11 and DR12 as well as DQA1*0401, *0501, *0601 and finally DPB1*0201 . These alleles show no linkage disequilibrium in the control population. (3) Rheumatoid factor positive polyarticular JA is associated, as is adult rheumatoid arthritis, with DR4 . Concerning the possible mechanisms of the immunopathogenesis, it is speculated that the normal function of HLA molecules, namely the presentation of antigenic peptides, plays a major role. Data collected on HLA associations in early onset pauciarticular JA have been interpreted as indicating that alleles of the DQA1 locus ( *0401, *0501, *0601 ) are probably responsible for presenting the hypothetical arthritogenic peptides. It is speculated that the pathogenic process includes the presentation of HLA-A2 or HLA-DPB1*0201 derived peptides presented by DQ molecules. It is clearly stated that typing for HLA alleles has very little or no importance for clinical diagnosis and prognosis.

OBJECTIVE:To characterize the clinical and immunogenetic features of patients with Mi-2 autoantibodies.METHODS:Eighteen adult white patients with Mi-2 antibodies were clinically characterized and compared with 41 Mi-2-negative dermatomyositis (DM) patients. HLA class I and class II typing for DRB alleles was done by microcytotoxicity assay and for DQA and DQB alleles by polymerase chain reaction-based oligotyping.RESULTS:Seventeen of the 18 Mi-2-positive patients had DM. Symptoms of scleroderma, lung involvement, and arthritis were less common in this group than in the Mi-2-negative DM patients; the V-sign rash and nailfold involvement were found more frequently. Mi-2 antibodies were strongly associated with HLA-DR7 (88% versus 24% in healthy controls), HLA-DQA1*0201 (86% versus 23%), and DR7 "homozygosity" (31% versus 0%). A tryptophan residue at position 9 of the HLA-DR beta chain was present in all Mi-2-positive patients (100% versus 62%; homozygous in 81% versus 15%).CONCLUSION:Our results reemphasize the specificity of Mi-2 antibodies for DM, and extend previous reports that Mi-2 antibody production is associated with certain HLA class II antigens. We propose beta 9-Trp as a candidate epitope on the HLA-DR beta chain as a prerequisite for this type of autoimmune response.

Diverse pathogenetic factors may lead to the complex syndrome of early graft dysfunction, an important determinant of later renal graft outcome. That humoral factors could play a prominent role in the development of the syndrome was suggested by the capillary deposition of complement fragment C4d in about 50% of graft biopsies. This study investigates whether the presumed classical activation of complement is derived from preformed antibodies that would possibly react against endothelial HLA-class II molecules. Such antibodies were detectable by flow cytometry using a representative collection of 11 DR-typed lymphoblastoid cell lines (LCL) as targets. Simultaneous discrimination between complement-activating and-nonactivating antibodies was achieved by two-color FACS analysis. Using this method, 44 out of 86 pretransplant serum samples from recipients with early dysfunction showed reactivity against LCL (18 complement-activating, 14 nonactivating, 12 complement-activating non-IgG). Conventional panel-reactivity was observed in 20 sera only (14 also LCL-reactive). Evaluation of corresponding graft biopsies revealed that capillary C4d was associated with LCL (P=0.018) and panel reactivity(P=0.015) alone and in combination(P=0.001; Pearson's chi-square test). Thirteen subsequent graft losses within one year were observed in the LCL-reactive group as compared with seven losses in the nonreactive group (panel-reactive: 7; non-reactive: 13). Thus, measurement of LCL-reactive antibodies in prospective transplant recipients improves the assessment of an individual immunological risk. The results further demonstrate that preformed antibodies do not simply reflect the enhanced overall immune reactivity of certain recipients but rather act locally in vivo, thus emphasizing the role of humoral factors in the development of early graft dysfunction.

Lymphotoxin (LT) and tumor necrosis factor‐α (TNF‐α) play an important role in the pathogenesis of multiple sclerosis (MS). MS is associated with the HLA‐DR2, Dw2, DQ6 HLA class II haplotype. Because both LT and TNF‐α are encoded in the HLA region, the HLA association of MS may be related to the production of these cytokines. To test this hypothesis, we investigated the production of LT, TNF‐α, and interferon‐γ (IFN‐γ) by CD4 + T‐cell lines (TCLs) specific for myelin basic protein (MBP) or tetanus toxoid (TT) isolated from MS patients and normal controls. After stimulation with specific antigen but not mitogen, TCLs from HLA‐DR2 + donors produced significantly more LT and TNF‐α, than TCLs from DR2 − donors. In contrast, HLA‐DR2 + and DR2 − TCLs did not differ in the production of IFN‐γ, a cytokine also produced by T cells but not encoded in the HLA region. Increased secretion of LT and TNF‐α was unrelated to the specificity (MBP vs TT), MHC restriction (HLA‐DR2 vs other DR molecules), or source (MS vs normal) of the TCLs. There was no significant association of the cytokine production with individual LT or TNF‐α alleles, indicating that the increased production of these cytokines may be linked to other polymorphic genes in this region. The results suggest that the association of MS with HLA‐DR2 implies a genetically determined propensity of T cells to produce increased amounts of LT and TNF‐α.

Vox SanguinisVolume 69, Issue 4 p. 359-372 Nomenclature for Factors of the HLA System, 1995 Julia G. Bodmer, Corresponding Author Julia G. Bodmer Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukImperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK)Search for more papers by this authorSteven G. E. Marsh, Steven G. E. Marsh Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorEkkehard D. Albert, Ekkehard D. Albert Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorWalter F. Bodmer, Walter F. Bodmer Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorRonald E. Bontrop, Ronald E. Bontrop Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorDominique Charron, Dominique Charron Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorBo Dupont, Bo Dupont Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorHenry A. Erlich, Henry A. Erlich Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorBernard Mach, Bernard Mach Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorWolfgang R. Mayr, Wolfgang R. Mayr Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorPeter Parham, Peter Parham Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorTakehiko Sasazuki, Takehiko Sasazuki Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorGeziena M. Th. Schreuder, Geziena M. Th. Schreuder Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorJack L. Strominger, Jack L. Strominger Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorArne Svejgaard, Arne Svejgaard Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorPaul I. Terasaki, Paul I. Terasaki Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this author Julia G. Bodmer, Corresponding Author Julia G. Bodmer Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukImperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK)Search for more papers by this authorSteven G. E. Marsh, Steven G. E. Marsh Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorEkkehard D. Albert, Ekkehard D. Albert Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorWalter F. Bodmer, Walter F. Bodmer Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorRonald E. Bontrop, Ronald E. Bontrop Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorDominique Charron, Dominique Charron Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorBo Dupont, Bo Dupont Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorHenry A. Erlich, Henry A. Erlich Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorBernard Mach, Bernard Mach Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorWolfgang R. Mayr, Wolfgang R. Mayr Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorPeter Parham, Peter Parham Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorTakehiko Sasazuki, Takehiko Sasazuki Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorGeziena M. Th. Schreuder, Geziena M. Th. Schreuder Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorJack L. Strominger, Jack L. Strominger Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorArne Svejgaard, Arne Svejgaard Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this authorPaul I. Terasaki, Paul I. Terasaki Tissue Antigen Laboratory Imperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX (UK) Telephone: 44 (UK)-171 (London)-269-3534 Fax: 44 (UK)-171 (London)-831-6786 email: marsh@icrf.icnet.ukSearch for more papers by this author First published: November 1995 https://doi.org/10.1111/j.1423-0410.1995.tb00376.xCitations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume69, Issue4November 1995Pages 359-372 RelatedInformation

Transcription of major histocompatibility complex class I genes is controlled by the class I regulatory complex in the 5′ flanking region. To investigate the molecular basis of this region, we studied the polymorphism of the promoter of the HLA-B locus extending from the ATG transcription initiation signal to —284 base pairs (bp) which includes a number of cis-acting elements: interferon response sequence (IRS), enhancer A and enhancer B. Genomic DNA from 35 homozygous cell lines from the 10th International Histocompatibility Workshop and from eight heterozygous panel members was amplified using two primers designed to specifically amplify the HLA-B locus. The double-stranded polymerase chain reaction products were sequenced using the cycle sequencing technique and an ABI 373A automatic sequencer. Promoter sequences of thirty-one different HLA-B alleles were determined in this study. Within the 284 bp upstream of the ATG signal, base substitutions were observed in 23 different nucleotide positions. Our study shows a high degree of polymorphism of the HLA-B promoter region, but conserved sequences of the known cis-acting elements with the exception of enhancer B in which there are two base substitutions for B7 and B42 (position −93 and position −95). The 23 polymorphic sites can be grouped into 12 different HLA-B promoter types (groups A to M) for 31 HLA-B locus alleles. Some of the groups of alleles sharing the same promoter sequence such as, for example, group A with B51 B52, B53, and B35, might have been predicted on the basis of serological similarity and/or exon 2, 3 sequence. In other groups, such as G (B18, B37, B27), it could not have been anticipated from serological experience that B18 and B27 carry the same promoter. Several sequencing errors were detected in the HLA-B promoter sequences published previously.

Tissue AntigensVolume 44, Issue 1 p. 1-18 Free Access Nomenclature for factors of the HLA system, 1994 Julia G. Bodmer, Corresponding Author Julia G. BodmerImperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX United Kingdom Tel. 44–71-269-3395 FAX 44–71-831-6786Search for more papers by this authorSteven G.E. Marsh, Steven G.E. MarshSearch for more papers by this authorEkkehard D. Albert, Ekkehard D. AlbertSearch for more papers by this authorWalter F. Bodmer, Walter F. BodmerSearch for more papers by this authorBo Dupont, Bo DupontSearch for more papers by this authorHenry A. Erlich, Henry A. ErlichSearch for more papers by this authorBernard Mach, Bernard MachSearch for more papers by this authorWolfgang R. Mayr, Wolfgang R. MayrSearch for more papers by this authorPeter Parham, Peter ParhamSearch for more papers by this authorTakehiko Sasazuki, Takehiko SasazukiSearch for more papers by this authorGeziena M. Th. Schreuder, Geziena M. Th. SchreuderSearch for more papers by this authorJack L. Strominger, Jack L. StromingerSearch for more papers by this authorArne Svejgaard, Arne SvejgaardSearch for more papers by this authorPaul I. Terasaki, Paul I. TerasakiSearch for more papers by this author Julia G. Bodmer, Corresponding Author Julia G. BodmerImperial Cancer Research Fund 44 Lincoln's Inn Fields London WC2A 3PX United Kingdom Tel. 44–71-269-3395 FAX 44–71-831-6786Search for more papers by this authorSteven G.E. Marsh, Steven G.E. MarshSearch for more papers by this authorEkkehard D. Albert, Ekkehard D. AlbertSearch for more papers by this authorWalter F. Bodmer, Walter F. BodmerSearch for more papers by this authorBo Dupont, Bo DupontSearch for more papers by this authorHenry A. Erlich, Henry A. ErlichSearch for more papers by this authorBernard Mach, Bernard MachSearch for more papers by this authorWolfgang R. Mayr, Wolfgang R. MayrSearch for more papers by this authorPeter Parham, Peter ParhamSearch for more papers by this authorTakehiko Sasazuki, Takehiko SasazukiSearch for more papers by this authorGeziena M. Th. Schreuder, Geziena M. Th. SchreuderSearch for more papers by this authorJack L. Strominger, Jack L. StromingerSearch for more papers by this authorArne Svejgaard, Arne SvejgaardSearch for more papers by this authorPaul I. Terasaki, Paul I. TerasakiSearch for more papers by this author First published: July 1994 https://doi.org/10.1111/j.1399-0039.1994.tb02351.xCitations: 207AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 WHO-Nomenclature-Committee. Bull. WHO 1968: 39: 483. 2 WHO-Nomenclature-Committee. WHO terminology report. In: P. I. Terasaki ed. Histocompatibility Testing, 1970, Copenhagen: Munksgaard, 1970: 49. 3 WHO-Nomenclature-Committee. Bull. WHO 1972: 47: 659. 4 WHO-Nomenclature-Committee. Bull. 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