Distribution Of DRB1 Research Articles

Comprehensive research on the distribution of HLA-DRB1 in Chinese populations.

By presenting antigen peptides, HLA-DRB1 plays an important role in the immune system. However, the allele frequency of HLA-DRB1 exon 2 across China has not been comprehensively studied, especially in minority populations. We sampled 3757 individuals from 59 population. The HLA-DRB1 region from 212 to 463 bp (NM_002124.4 exon 2) in each population was sequenced by Sanger sequencing and genotyped via SBTengine® software, and the allele frequency was calculated by GenAlEx 6.5. Eighty-two DRB1 alleles were identified. The expected heterozygosity of DRB1 was lower in the south than in the north, which was inconsistent with the Y chromosome and mitochondrial DNA results. The Mantel test and nonparametric correlation analysis showed that the correlations of the genetic distance with geographical distance and of DRB1 allele frequencies with latitude weakened after the southern and northern groups were considered separately. Principal coordinate analysis showed that populations speaking the same languages were not codistributed. Compared with other genetic markers, the distribution of DRB1 seems less affected by geographic distance and ethnic origin. Local factors such as gene flow with neighbouring populations, geographic isolation or natural selection are important forces shaping the DRB1 gene pool of local populations.

HLA-A -B and -DRB1 distribution in Kami: A caste population of Gorkha community from the sub-Himalayan region of West Bengal, India

The present investigation is the first of its kind to understand the HLA profile of Kami population from the Indian Gorkha community of sub-Himalayan West Bengal, India. A total of 158 individuals from Kami population were genotyped at first field resolution by HLA ABDRB1 PCR SSP typing kit. The genotype assignment to the individuals was performed by Ready Gene V.1.0.0.0′ software. The data were analysed by PopWin32-0.7.0 software. All the loci typed were in Hardy-Weinberg equilibrium. The genotype data is accessible at Allele Frequencies Net Database with the name India, sub-Himalayan West Bengal, Kami number 3720.

Comprehensive assessment of association between HLA polymorphisms and acute leukemia in Iranian population

Immune system has a prominent role in both prevention and treatment of leukemia. Based on the role of human leukocyte antigen (HLA) in determination of response to therapeutic options and risk of development of leukemia, several studies have addressed association between HLA alleles and this disorder. Here, we conducted a single-center analysis of HLA-A/-B/-DRB1 distribution in Iranian patients with acute leukemia. The study enrolled 92 patients with acute lymphoblastic leukemia (ALL), 76 patients with acute myeloid leukemia (AML) and 90 healthy controls. HLA-A/-B/-DRB1 alleles were identified using PCR method with sequence specific primers. There was no significant difference in distribution of HLA-A/-B/-DRB1 alleles between three study subgroups. However, distribution of HLA-A-B-DRB1 haplotypes was significantly different between AML and ALL patients and between both groups of patients and controls (P<0.0001). The results of the current study should be verified in future studies with larger sample sizes.

Association of human leukocyte antigen-DRB haplotype in multiple sclerosis population of Khuzestan, Iran

Background: One of the demyelinating and inflammatory diseases of the central nervous system (CNS) is multiple sclerosis (MS). Though pathogenesis of MS is still unknown, both genetic and environmental factors are involved. The human leukocyte antigen (HLA) class-II alleles including HLA-DRB5*01, DQB1*0602, DRB1*1501, and DQA1*0102 may have remarkable effect in MS risk although it is controversial in studies. As there is no data with respect to the HLA-DRB1*1501-DRB5*01 correlation with MS in Khuzestan Province, Iran, the goal of the survey was to investigate the association of this haplotype with MS in this population. Methods: The study focused on DRB5*01-DRB1*1501 haplotype association with MS in 200 patients and 200 healthy individuals. Typing of HLA was carried out by polymerase chain reaction (PCR) amplification with sequence-specific primers (SSP) method. SPSS software was used for the statistical analyses. Results: No association between DRB5*01+-DRB1*1501+ and MS was found (P = 0.156). Distribution of DRB1*1501+-DRB5*01- (carrying DRB1*1501+ but not DRB5*01-) and DRB1*1501--DRB5*01- haplotypes was statistically different between patients and controls (29.73% vs. 11.81%, P < 0.001) and (42.16% vs. 68.50%, P < 0.001), respectively. However, DRB1*1501--DRB5*01+ revealed no association with MS (15.13% vs. 11.81%, P = 0.403). HLA-DRB1*1501--DRB5*01+ was significantly more frequent among female patients with MS (16.19% vs. 6.12%, P = 0.019) and Persian group (17.11% vs. 5.79%, P = 0.027). Positive correlation of HLA-DRB1*1501+-DRB5*01- haplotype with the expanded disability status scale (EDSS) steps from 5 to 10 was observed (62.50% vs. 25.76%, P = 0.026). Moreover, no meaningful association was shown among the haplotypes with EDSS, course of MS, ethnicity, and gender. Conclusion: Our findings suggest that DRB1*1501+-DRB5*01- and DRB1*1501--DRB5*01- haplotypes may have positive association with MS risk. Also, this survey indicates that HLA-DRB1*1501--DRB5*01+ is involved in susceptibility of the disease among women and Persians. DRB1*1501+-DRB5*01- genotype frequency may have a key role in MS developing.

Human leukocyte antigen-A*33:03-B*58:01-DRB1*15:140, a deduced probable human leukocyte antigen haplotype in association with a human leukocyte antigen low-incidence allele DRB1*15:140 in Taiwanese individuals: A case analysis.

Objective:Human leukocyte antigen (HLA)-DRB1*15:140 is a low-frequency allele in the HLA-DRB1 locus. The aim of this study is to confirm the ethnicity of DRB1*15:140 and to deduce a probable HLA-DRB1*15:140-associated HLA haplotype in Taiwanese individuals.Materials and Methods:A total of 1815 healthy unrelated Taiwanese individuals and 14,562 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exons 1 and 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols.Results:The DNA sequence of HLA-DRB1*15:140 is identical to DRB1*15:02:01:01 in exons 1 and 2, except at residue 91 of DRB1*15:02:01:01 where a G in DRB1*15:02:01:01 is replaced by an A in DRB1*15:140 (codon 2; GAC->AAC). The nucleotide substitution in exon 1 introduces a one amino acid substitution at residue 2 where an aspartic acid (D) in DRB1*15:02:01:01 is replaced by an asparagine (N) in DRB1*15:140. We deduced the probable HLA haplotype associated with DRB1*15:140 in Taiwanese to be HLA-A*33:03-B*58:01-DRB1*15:140.Conclusion:Information on the ethnicity and distribution of DRB1*15:140 and its deduced probable HLA haplotype in association with the low-incidence allele is of value for HLA-testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Analysis of HLA-DRB1*1501 in Multiple Sclerosis Patients in Khuzestan Province, Iran

Background: Multiple sclerosis (MS) is a demyelinating, autoimmune and neurodegenerative disease of the central nervous system (CNS). The pathogenesis of this disease is still unknown, although there are evidences of environmental factors affecting subjects with genetic predisposition factors. The contribution of HLA-DRB1*1501 to MS risk has been replicated and confirmed in most population-based studies. Since there are no data with respect to the association of HLA-DRB1*1501 and MS in Khuzestan province. Objectives: The aim of this study was to investigate the correlation of this allele with MS in Khuzestan province. Methods: In this case-control study, DRB1*1501 allele was analyzed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 200 MS patients and 200 unrelated healthy individuals, without any autoimmune disease from the same geographical region. The frequencies of the mentioned allele were compared between the patients and control group using SPSS 16 statistical software and the chi square test. Results: The results demonstrated that distribution of DRB1*1501 allele was statistically different between patient and control (41.5% vs. 22.81%, P < 0.001); significant correlation was observed among these allele with both Arab (28.84% vs. 50.84%, P = 0.005) and Persian (15.87% vs. 35.55%, P = 0.018) ethnicities; although no association was revealed between mentioned allele and disease clinical course (relapsing-remitting, secondary-progressive, progressive-relapsing and primary-progressive), expanded disability scale score (EDSS) and gender. Conclusions: The study presents association of susceptibility to multiple sclerosis in southwest of Iran with HLA-DRB1*1501 allele in both Arab and Persian ethnic; although DRB1*1501 may be is not involved in the pathogenesis of different MS disease subtypes. The results are consistent with most of the other studies in Iran; and also most studies in European populations.

HLA class II alleles and risk for peripheral neuropathy in type 2 diabetes patients.

The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.

HLA Distribution in COPD Patients

Background: Auto-immunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), particularly to the presence of emphysema. Auto-immune diseases are characterized by an abnormal distribution of HLA class II alleles (DR and DQ). The distribution of DRB1 and DQB1 alleles has not been investigated in COPD. Methods: To this end, HLA medium-low resolution typing was performed following standardized protocols in 320 clinically stable COPD patients included in the PAC-COPD study. Results were compared with controls of the same geographical and ethnic origin, and potential relationships with the severity of airflow limitation and lung diffusing capacity impairment were explored in patients with COPD. Results: The distribution of DRB1 and DQB1 alleles in COPD was similar to that of controls except for a significantly higher prevalence of DRB1*14 in patients with severe airflow limitation and low diffusing capacity. Conclusions: By and large, HLA distribution was similar in COPD patients and controls, but the HLA class II allele DRB1*14 may contribute to the pathogenesis of severe COPD with emphysema.

Relative Immunogenicity of Fya and K Antigens Based on HLA Class II Restriction Analysis.

Background: The relative immunogenicity of protein red blood cell antigens is a longstanding observation. The immunogenicity of a specific antigen has been evaluated first by comparing the observed frequency of alloantibodies with the calculated frequency of the opportunity for immunization. For example in the Caucasian population, it can be deduced that K antigen is 9 times more immunogenic than Fya antigen. The aim of this work was to elucidate the underlying mechanisms of the protein red blood cell relative immunogenicity.Study Design: We chose the model of K and Fya antigens since both result from of a single nucleotide polymorphism and present different levels of immunogenicity. 29 individuals producing anti-Fya and 30 producing anti-K alloantibodies were analyzed. Each individual was selected according to the presence of only one antibody: Fya or K specificity. FY* and KEL* genotyping was performed using the real time fluorescence PCR method. All individuals were Caucasian. DRB1* polymorphisms were determined at the generic level by reverse dot-blot hybridization. DRB1*04 was determined at the allelic level by PCR-SSP. The observed DRB1* frequencies were compared to those of a previously published control population of 350 Caucasian individuals. The TEPITOPE algorithm was applied to predict DRB1*-binding peptide sequences containing the specific K and Fya polymorphisms.Results: Within the anti-Fya group, the DRB1*04 was the unique restriction molecule as the DRB1*04 phenotypic frequency was 100%. In the control population, the DRB1*04 phenotypic frequency was 19.01%. The frequency of DRB1*04 was significantly higher as compared to the control population (P<0.0001). The distribution of DRB1*04 alleles was scattered. Conversely, within the anti-K group, a high degree of histocompatibility promiscuity was observed as numerous DRB1* molecules corresponding to the predominant molecules in the Caucasian population were identified.The DRB1* peptide binding motif prediction algorithm TEPITOPE confirmed these findings and evidenced a higher DRB1* affinity for K-derived peptides as compared to Fya-derived peptides.Conclusion: These results show that DRB1*04 is the major restriction molecule for Fya-derived peptides and suggest that when stimulated, only 19.01% of Caucasians are capable of binding the Fya-derived peptides and producing anti-Fya antibodies. Conversely, all or nearly all individuals in the general population are capable of binding the K-derived peptides and therefore could produce, when stimulated anti-K antibodies.These results suggest that within a particular ethnic group, the intrinsic immunogenicity of a given red blood cell antigen is related both to the nature of the antigen (number and affinity of potential derived peptides) and to the distribution within the population of DRB1* molecules capable of presenting the derived peptide to the T lymphocyte. Although this first immunological signal is crucial for initiating the immunologic response, future studies regarding T lymphocyte recognition will be necessary in order to fully understand red blood cell immunogenicity.

Relative AHLA-DRB1*04 allele frequencies in five United States populations found in a hematopoietic stem cell volunteer donor registry and seven new DRB1*04 alleles

The frequencies of 29 HLA-DRB1*04 alleles were determined for five major U.S. populations found within a hematopoietic stem cell volunteer donor registry. One hundred sixty-one DRB1*04 positive individuals from each of the self-described groups, Caucasians, African-Americans, Asian/Pacific Islanders, Hispanics, and Native Americans, were randomly chosen from a database of 82,979 unrelated persons. Subjected to polymerase chain reaction–sequence-specific oligonucleotide probe (PCR-SSOP) typing, these 805 individuals carried a total of ten different DRB1*04 alleles, ranging from DRB1*0401 to DRB1*0411 with DRB1*0409 conspicuously absent from all five groups. The distribution of DRB1*04 alleles varied among the groups, with DRB1*0401 being predominant in Caucasians, African-Americans, and Native Americans. DRB1*0404 and DRB1*0407 were the two most commonly observed alleles in Hispanics, whereas DRB1*0405 and DRB1*04031 were most common in Asian/Pacific Islanders. The remaining 18 DRB1*04 alleles known at the time of the study were not observed. Although not observed in the frequency study, seven previously unreported DRB1*04 alleles are also described.

Distribution of DRB1 and DQB1 HLA class II alleles in occupational asthma due to western red cedar.

Occupational asthma caused by western red cedar is a common problem in sawmill industries. The objective of this study was to examine a possible association of human leukocyte antigen (HLA) class II genetic markers with susceptibility or resistance to western red cedar induced asthma. The distribution of DRB1 and DQB1 HLA class II alleles and DRB1-DQB1 haplotypes was studied in 56 Caucasian patients with proven red cedar asthma and 63 healthy Caucasian control subjects exposed to red cedar dust. DRB1 and DQB1 high resolution typing was performed by the polymerase chain reaction-based method. Patients with red cedar asthma had a higher frequency of HLA DQB1*0603 and DQB1*0302 alleles compared to a group of healthy exposed control subjects and a reduced frequency of DQB1*0501 allele. The frequency of the DRB1*0401-DQB1* 0302 haplotype was increased and the DRB1*0101-DQB1*0501 haplotype was reduced. These findings suggest that genetic factors such as human leukocyte antigen class II antigens may be associated with susceptibility or resistance to development of red cedar asthma.

Worldwide differences in the incidence of insulin autoimmune syndrome (Hirata disease) with respect to the evolution of HLA-DR4 alleles

The relationship between the geographic distribution of susceptibility genes to insulin autoimmune syndrome (IAS) and the incidence of insulin autoimmune syndrome was investigated in order to examine the distribution of the genetic background to susceptibility to certain diseases. The HLA-DR4 allele, DRB1∗0406, is associated with increased susceptibility to IAS among Japanese, while the DRB1∗0403 and DRB1∗0407 alleles are not (the odds ratio of which are 1.6 and1.1, respectively). The worldwide geographic distribution of the three DR∗04 alleles showed that the distribution of DRB1∗0403 encompassed that of DRB1∗0406 and DRB1∗0407. Taken together with the findings that Glu at position 74 in the DRB1 molecule is shared by the three DRB1∗04 alleles, there are only a few differences between the DRB1 molecule-nucleotide sequences of DRB1∗0403, DRB1∗0406 and DRB1∗0407, and that all the three DRB1∗04 alleles are carried by the same class II haplotype, DQA1∗0301/DQB1∗0302, it may be considered that DRB1∗0403 is the ancestral allele of DRB1∗0406 and DRB1∗0407. Therefore, populations with a higher prevalence of DRB1∗0406 have a higher risk of developing IAS. The extremely low prevalence of IAS among Caucasians can be explained by the low prevalence of DRB1∗0406 in this population. This is a good example of the association between the predisposition to risk of development of certain diseases and the evolution of susceptibility genes.

MHC class II gene associations with autoantibodies to U1A and SmD1 proteins.

Autoantibodies against U small nuclear ribonucleoproteins (snRNP) are frequently present in the serum of patients with systemic rheumatic diseases, and have been reported to be associated with HLA-DR and -DQ genes. To better define the role of HLA genes in the production of such antibodies, we studied immunogenetic associations with autoantibodies reacting with U1 RNP, U1A and SmD1 proteins, and synthetic peptides containing immunodominant linear epitopes of these proteins. Only two out of the 15 overlapping peptides of U1A (i.e. peptides 35-58 and 257-282) and three of 11 peptides of SmD1 (i.e. peptides 1-20, 44-67 and 97-119) were significantly recognized by patients' sera selected on the basis of their antibody positivity with RNP in immunodiffusion. The distribution of DRB1, DQB1 and DPB1 alleles among the anti-RNP antibody-positive patients (n = 28) and healthy control subjects was similar. Antibodies against U1A (tested in Western immunoblotting with HeLa cell extracts) were positively associated to DRB1*06 allele; antibodies reacting with SmD1 peptide 44-67 were negatively associated to DRB1*02 and DQB1*0602 alleles. No association was found between DPB1 alleles and antibodies reacting with U1A and SmD1 antigens. This first study reporting an association between autoantibodies reacting with U1A and SmD1 proteins (and peptides of these proteins), and immunogenetic markers suggest that the production of antibody subsets directed against different components (or regions of these proteins) bound to the same snRNP particle is associated with distinct MHC class II alleles.

Contribution of DRB1*04 variants to predisposition to or protection from insulin dependent diabetes mellitus is independent of dq.

Certain DQ alpha/beta dimeric molecules have been shown to play a major role in determining susceptibility or resistance to IDDM. Whether or not predisposition associated with DR4 haplotypes is exclusively due to linkage to DQB1*0302 and DQA1*0301 alleles is still a controversial issue. A modifying effect of certain DRB1*04 subtypes on the susceptibility encoded by DQ alleles is possible, since not all DRB1*04-DQB1*0302 haplotypes are associated with the disease. The distribution of DRB1*04 subtypes was analysed in 240 DR4-positive Caucasian IDDM patients and 110 DR4-positive healthy controls using allele-specific hybridization after genomic amplification. Although an important contribution to IDDM predisposition was encoded by the DQB1*0302 allele which was found in the majority of patients (94.2% vs 64.7% in controls, Odd's ratio OR = 8.8, P < 0.0001), differences between DRB1*04 variants persisted after the effect of the DQB1 locus was removed by matching patients and controls for DQB1*0302. Thus, the DRB1*0402 allele conferred a strong IDDM-predisposing effect (OR = 3.1, P < 0.02) which was highly significant in the absence of DR3 on the second haplotype (OR = 5.6, P < 0.0001) but was not visible among DR3/4 heterozygote individuals. Conversely, the DRB1*0404 allele conferred a strong protective effect (OR = 0.26, P < 0.0001) which was dominant even in the presence of the associated high risk DR3 haplotype (OR = 0.21, P < 0.03). These data indicate that DQ molecules are not the sole contributors to the DR4-associated IDDM predisposition, and that peculiar DR4 subtypes play a significant role in susceptibility to or protection from the disease. DRB1*0402 differs from DRB1*0404 by only two acidic residues at positions 70 and 71 within the peptide binding groove, instead of amide and basic amino acids. This might induce changes of peptide binding specificity that correlate with the genetic linkage of IDDM predisposition.

Multiple basal cell carcinomas: no association withHLA-DRB, HLA-DQAIorHLA-DQBIin Swedish patients

Many diseases with autoimmune features are associated with alleles of the human leucocyte antigen (HLA). However, few if any malignant disorders have reproducibly been shown to be HLA-associated. In three independent studies, using serological tissue typing techniques, an increase of the HLA class II specificity DR1 has been found in patients with multiple basal cell carcinomas. These observations prompted us to determine the frequencies of DRB1, DQA1, and DQB1 alleles by high-resolution genomic tissue-typing methods, including subdivision of the serological DR1 specificity in the four sequence-defined alleles, DRB1*0101 to DRB1*0104, in 50 unrelated Swedish patients with a history of four or more basal cell carcinomas and 250 healthy controls. The frequency of DR1 was the same in patients and controls (18%). All DR1-positive patients and controls carried the DQA1*0101 and DQB1*0501 alleles. Six of the nine DR1-positive patients and controls carried the DQA1*0101 and DQB1*0501 allels. Six of the nine DR1-positive patients were DRB1*0101-positive, one DRB1*0102 and two carried the DRB1*0103 allele. This distribution of DRB1*01 alleles did not differ from the one found in the controls. We conclude that genetic factors associated with the HLA class II region do not contribute significantly to the aetiology of multiple basal cell carcinomas.

HLA-DRB1*0401 is associated with susceptibility to insulin-dependent diabetes mellitus independently of the DQB1 locus.

The distribution of DRB1*04 alleles and DRB1/DQB1 haplotypes was analysed in 57 DR4+ caucasoid subjects with insulin-dependent diabetes mellitus (IDDM) and 96 DR4+ healthy controls selected on the basis of DR serology, and the findings were analysed in relation to age at diagnosis of IDDM. DNA samples were amplified using specific DR and DQ primers and hybridized with sequence-specific oligonucleotide probes. A significantly increased combined frequency of DRB1*0401 and 0402 was observed in IDDM subjects aged < or = 12 years at diagnosis (allele frequency 88.4% compared with 62.0% in controls, P < 0.025). There was a non-significant increase in DRB1*0401 and 0402 in IDDM subjects < or = 12 years when compared with IDDM subjects > 12 years (P < 0.1). DRB1*0404 was decreased in the total IDDM subject group compared with controls (4.8% vs. 19.0%, P < 0.025) but did not reach statistical significance in the individual age at diagnosis groups. In contrast, the frequency of DQB1*0302 was increased uniformly across both ages at diagnosis groups. In controls DRB1*0401 occurred in haplotype association with DQB1*0301 in a significantly greater frequency than with DQB1*0302. However, 95.0% of DRB1*0401 IDDM subjects were DQB1*0302. DRB1*0404, which was decreased in frequency in IDDM subjects, occurred in association significantly more frequently with DQB1*0302 in controls. These results imply that DRB1 and DQB1 have independent roles as HLA susceptibility genes in IDDM. DQB1 may have a permissive role whereas DRB1 could influence the rate at which underlying disease progresses to clinical IDDM.

Distribution of MHC class II alleles in primary systemic vasculitis

Previous studies have shown a number of different associations between major histocompatibility complex (MHC) alleles and primary systemic vasculitis. Disease heterogeneity and the lack of specificity of certain MHC typing techniques may have contributed to the lack of consistency in those studies. We therefore studied a relatively homogeneous group of 94 patients with Wegener's granulomatosis, microscopic polyangiitis, or renal-limited vasculitis using molecular techniques that allow more precise assignment of MHC genotype. DNA was prepared from peripheral blood and DRB1 genotype determined by Taq restriction fragment length polymorphism. DQB1 and DPB1 genotype were assigned by polymerase chain reaction amplification followed by probing with allele-specific oligonucleotides. Specificity of associated anti-neutrophil cytoplasm antibodies (ANCA) was determined where possible by solid phase immunoassays using purified proteinase 3 (PR3) and myeloperoxidase (MPO). After correction for multiple comparisons there were no significant differences in the distribution of DRB1, DQB1 and DPB1 alleles between a local control group (N = 90 for DRB1, N = 50 for DQB1 and DPB1) and the patient group as a whole (N = 94) or two a priori defined subgroups (anti-PR3 positive, N = 35; anti-MPO positive, N = 22). We have therefore found no significant association between primary systemic vasculitis and any MHC class II allele. This, together with the fact that previous smaller studies have shown no consistent association, suggests that any such association is very weak, if it exists at all.

Distribution of HLA class II alleles among Norwegian caucasians

We report genomic HLA class II typing of 181 randomly selected Norwegian controls. Seventeen DRB1, 7 DQA1, 10 DQB1, 2 DPA1, and 16 DPB1 alleles were found in the tested population. HLA class II antigen and allele frequencies are given, as well as the distribution of DRB1, DQA1, DQB1 haplotypes. Linkage disequilibrium between some DPB1 alleles and DRB1 and/or DQB1 alleles are also reported.