The HLA Dictionary 2004: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents serological equivalents of HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5 and -DQB1 alleles. The dictionary is an update of that published in 2001. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP), recent publications and individual laboratories. This latest update of the dictionary is enhanced by the inclusion of results from studies performed during the 13th International Histocompatibility Workshop and from neural network analyses. A summary of the data as recommended serological equivalents is presented as expert assigned types. The tables include remarks for alleles, which are or may be expressed as antigens with serological reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated haematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. The serological DNA equivalent dictionary will also aid in typing and matching procedures for organ transplant programmes whose waiting lists of potential donors and recipients comprise mixtures of serological and DNA-based typings. The tables with HLA equivalents and a questionnaire for submission of serological reaction patterns for poorly identified allelic products will be made available through the WMDA web page (http://www.worldmarrow.org) and, in the near future, also in a searchable form on the IMGT/HLA database.

The HLA Dictionary 2004: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents serologic equivalents of human leucocyte antigen (HLA)-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5 and -DQB1 alleles. The dictionary is an update of the one published in 2001. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for factors of the HLA System, the International Cell Exchange, the National Marrow Donor Program, recent publications and individual laboratories. This latest update of the dictionary is enhanced by the inclusion of results from studies performed during the 13th International Histocompatibility Workshop and from neural network analyses. A summary of the data as recommended serologic equivalents is presented as expert assigned types. The tables include remarks for alleles, which are or may be expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. The serological DNA equivalent dictionary will also aid in typing and matching procedures for organ transplant programs whose waiting lists of potential donors and recipients comprise of mixtures of serologic and DNA-based typings. The tables with HLA equivalents and a questionnaire for submission of serologic reaction patterns for poorly identified allelic products will be made available through the WMDA web page: www.worldmarrow.org. and in the near future also in a searchable form on the IMGT/HLA database.

HLA class II alleles are not a general susceptibility factor in Guillain-Barré syndrome.

OBJECTIVE: To assess whether human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles confer susceptibility to Guillain-Barre syndrome (GBS) or are related to specific clinical or serologic subgroups of GBS. METHODS: The HLA-DRB1 and HLA-DQB1 loci were genotyped by PCR amplification with sequence-specific primers in 164 well-documented Dutch patients with GBS and 207 healthy Dutch control subjects. Patients with GBS were divided into subgroups based on clinical features, severity of disease, antecedent infection, and anti-ganglioside antibodies. Data were compared with those of all case-control HLA studies in GBS performed previously. RESULTS: In this case-control study, HLA-DRB1 and HLA-DQB1 alleles did not differ between GBS patients and control subjects. The frequency of HLA-DRB1*01 was increased in patients who needed mechanical ventilation (odds ratio 4.2; 95% CI 1.9 to 9.6; p(c) = 0.02). Multivariate logistic regression analysis showed that this association was independent of the severity of paresis and the presence of cranial nerve involvement (all p < 0.05). There was a tendency toward an association between certain HLA alleles and several anti-ganglioside antibodies. CONCLUSIONS: Human leukocyte antigen (HLA) class II antigens are not a general susceptibility factor in Guillain-Barre syndrome (GBS). However, HLA class II alleles may be a determinant in distinct subgroups of GBS, indicating the need for further exploration in large-scale studies.

Associations with autoimmune disorders and HLA class I and II antigens in inclusion body myositis.

Whether autoimmune mechanisms play a role in the pathogenesis of inclusion body myositis (IBM) is unknown. Human leukocyte antigen (HLA) analysis in 52 patients, including 17 with autoimmune disorders (AIDs), showed that patients were more likely to have antigens from the autoimmune-prone HLA-B8-DR3 ancestral haplotype than healthy control subjects, irrespective of the presence of AIDs. Patients lacked the apparently protective HLA-DR53 antigen. The results provide further support for an autoimmune basis in IBM.

Five newly identified HLA alleles: A*0310, A*2907, B*4435, Cw*0206, Cw*0506, and confirmation of A*3106, B*3924, Cw*0314, DRB1*0322, and DRB1*1433 alleles.

A number of HLA alleles have been newly identified. This concerns HLA-A*0310, A*2907, B*4435, Cw*0206, Cw*0506, of which Cw*0206 was found in three unrelated individuals, all B*4002 positive. Some other alleles are also presented but confirm earlier detected sequences: A*3106, Cw*0314, DRB1*0322, and DRB1*1433. Moreover, we identified B*3924 in a bone marrow transplant recipient and in five of six unrelated stem cell donors, selected for this patient. In all cases, B*3924 was found on a haplotype combining A*0201, B*3924, Cw*0701, and DRB1*1303. The observation of this extended haplotype is of importance for the selection for stem cell transplantation. Cells expressing B*3924 and B*4435 were typed by serology as B39 and B44, respectively. Cells expressing HLA-A*0310 do not express A3 but type as A-Blank.

A novel B*38 allele, B*3809, was identified via sequence -based typing of B-cell line no. 299 of the UCLA International Cell Exchange.

In this paper we report the identification of a new HLA-B allele in a sample that was distributed in the International UCLA Terasaki Cell/DNA Exchange, and the results were summarized in the final report of the 280th Cell Exchange. This novel allele officially designed B*3809 was found in B-cell line no. 299 from a Dutch Caucasoid donor and differs from B*3801 by mutation C-->G at position 483 in exon 3, resulting in an amino-acid substitution at codon 161 from aspartic acid in B*3801 to glutamic acid in B*3809, respectively.

Histocompatibility and corneal transplantation.

BACKGROUND: HLA typing and matching have been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations were performed by a single surgeon in a single center between 1976 and 1996. Population genetic and other statistical analyses were performed. Simulation studies assessed the effects of HLA-DR mistypings on analytical results. RESULTS: Mono- and multivariate analyses identified retransplantation, degree of vascularization, HLA-AB and -DR match grades, endothelial cell count, graft size, recipient gender, storage method and panel-reactive antibodies as significantly influencing the survival of corneal transplants. Simulation studies showed that the beneficial effect of HLA-DR matching is abrogated by HLA-DR mistypings. CONCLUSIONS: Corneal transplant recipients have a normal immune response to HLA incompatibilities. Demonstration of that fact requires accurate HLA typings.

HLA haplotypes and susceptibility to rheumatoid arthritis. More than class II genes.

Our aim was to examine, using microsatellite (ms) markers, the contribution of the telomeric part of the HLA region to rheumatoid arthritis (RA) predisposition in the Spanish population. We have looked at the distribution of DQB1, DRBI and five ms loci (D6S1014, D6S273, D6STNFa, MIB and C1-2-5) within the HLA region in 147 Spanish RA patients and 202 control subjects. A total of 19 conserved ms configurations were observed, twelve of them in linkage disequilibrium with particular DQB1-DRB1 haplotypes. Interestingly, haplotype c1 (DQB1*0201-DRB1*0301-D6S1014*143-D6S273*139-D6STNFa*99-MIB*350-C1-2-5*196) was significantly associated with RA predisposition. As part of this haplotype, the MIB*350 allele was found to be a risk factor independently of the RA-predisposing haplotypes. The present results along with data from others prove the existence of a second predisposing locus located inside the MHC region, and suggest that might be located within the TNFa-HLA-B region.

Sarcoid arthritis: clinical characteristics, diagnostic aspects, and risk factors.

OBJECTIVES: (a) To describe the clinical characteristics of acute sarcoid arthritis and the diagnostic value of its presenting clinical features; (b) to evaluate whether disease onset is seasonal; and (c) to evaluate whether smoking behaviour or the presence of HLA class II alleles is a risk factor for the disease. METHODS: 579 consecutive patients with recent onset arthritis who had been newly referred to a rheumatology outpatient clinic were included in a prospective cohort study. The presenting clinical features, the smoking behaviour, and the results of HLA-DQ and HLA-DR DNA typing of 55 patients with sarcoid arthritis, 524 patients with other arthritides of recent onset, and samples of the normal population were compared. RESULTS: In all cases the disease showed a self limiting arthritis and overall good prognosis. The diagnostic ability of a combination of four clinical features--symmetrical ankle arthritis, symptoms of less than two months, age below 40 years, and erythema nodosum--was exceptionally high. When test positivity is defined as the presence of at least three of four criteria the set rendered a sensitivity of 93%, a specificity of 99%, a positive predictive value of 75%, and a negative predictive value of 99.7%. The disease clustered in the months March-July. The disease was negatively associated with smoking (odds ratio (OR) 0.09; 95% confidence interval (95% CI) 0.02 to 0.37) and positively associated with the presence of the DQ2 (DQB1*0201)-DR3 (DRB1*0301) haplotype (OR 12.33; 95% CI 5.97 to 25.48). CONCLUSION: The disease entity acute sarcoid arthritis has highly diagnostic clinical features. The seasonal clustering, the protective effect of smoking, and the association with specific HLA class II antigens support the hypothesis that it results from exposure of susceptible hosts to environmental agents through the lungs.

Influence of HLA polymorphism on persistent remission in rheumatoid arthritis.

BACKGROUND: Several studies have reported an association between the presence of the shared epitope (SE) and susceptibility to rheumatoid arthritis (RA). Recent studies have shown that certain HLA-DRB1 alleles in combination with predisposing DQB1 and DQA1 alleles may protect against the development of RA. This model is known as the rheumatoid arthritis protection (RAP) hypothesis. OBJECTIVE: To determine the distribution of HLA-DRB1 and DQB1/DQA1 alleles in a cohort of patients with RA in remission and to determine the association between these HLA alleles and the persistence of remission. PATIENTS AND METHODS: HLA-DRB1 and DQB1 typings were performed in 167 patients with RA in remission, defined according to the American College of Rheumatology criteria. The disease course, as defined by the persistence of remission during a follow up of two years, was compared between subgroups. According to the RAP hypothesis patients were divided into three subgroups: patients carrying predisposing DQ alleles, patients carrying predisposing alleles in combination with protective alleles (DQ(RA+)/DERAA phenotype), and patients lacking the predisposing alleles. According to the SE hypothesis, patients were divided into three subgroups based on whether they were carrying two, one, or no predisposing alleles (SE alleles). RESULTS: Predisposing DQ alleles along with a DERAA-bearing allele were present in 14 (8%) of the 167 patients. At least one SE allele was present in 116 (69%) patients; 34 of them (20%) were carrying two copies. The disease course was not significantly different between the subgroups according to the SE and RAP hypothesis, respectively. CONCLUSION: The frequency of DQ(RA+)/DERAA combinations and of SE alleles in patients with RA clinically in remission was similar to that found in other RA populations. Persistent remission of RA was not associated with any particular HLA subtypes, indicating that HLA typing is not useful for predicting persistent clinical remission.

THE SPECIFICITY OF ANTI-HLA CLASS II MONOCLONAL ANTIBODIES IN CATTLE.

At the Eleventh International HLA Histocompatibility Workshop, numerous anti-HLA class II monoclonal antibodies (mAb) were tested. For several of the polymorphic mAb, one epitope for binding has been mapped within the antigen-binding site of the class II molecules. Screening of the available bovine DRB3 and DQB exon 2 sequences revealed that some of the key amino acid (AA) motifs of these epitopes were present in cattle as well, and the question was raised whether this sharing of key AA motifs might cause interspecies cross-reactivity. Eight polymorphic anti-HLA class II mAb (seven anti-HLA DRB1 and one anti-HLA DQB) were selected for analysis of their reactivity towards bovine lymphocytes. In addition, the monomorphic anti-HLA class II mAb, 7.5.10.1, was selected for analysis, as this mAb was described to detect class II polymorphism in cattle. Flow cytometry and lymphocyte microcytotoxicity testing revealed that five of the polymorphic anti-HLA mAb were reactive with bovine lymphocytes. Furthermore, the anti-bovine reactivity of 7.5.10.1 was confirmed. These findings were supported by biochemical analysis. The anti-bovine reaction of the anti-HLA mAb did not correspond with the expected reaction, which was based on the presence of the AA, postulated to be responsible for recognition. Therefore, we suggest that the patterns of reactivity of the anti-HLA mAb are not always determined by one epitope.