HLA Bw46 and DR9 associations in Graves' disease of Chinese patients are age- and sex-related

The HLA-A, -B antigens in 159 Chinese patients with Graves' disease were compared with those of 330 controls. The HLA-DR antigens of the patients were also studied in 100 normals. Analysis of the increased prevalence of Bw46, according to the sex and age of onset of disease of the patients, showed that the strong association of Bw46 resided with male patients (n = 58), Pc = 0.0000052, RR = 4.2. Although the frequency of Bw46 was also increased in female patients (n = 101), it was statistically not significant. For the DR9 antigens, the strong association with male patients was also observed, viz. Pc = 0.019, RR = 3.2. Males also had higher risks of Graves' disease if they had homozygous Bw46 at presentation. Further analysis by age of onset of disease revealed the segregation of significant association with Bw46 for the males at 1-19 yr, Pc = 0.0011, RR = 17.5 HLA associations (Bw46 and DR9) with Graves' disease in Chinese are observed primarily in males, especially those whose known ages of onset of the disease are between 1-19 yr (Bw46).     

The effects of HLA class II genes on the susceptibility to autoimmune thyroid diseases

Immunogenetic factors such as HLA, C4, T cell receptor and immunoglobulin allotypes were investigated in 115 Japanese patients with Graves' disease. The patients showed strong positive association with HLA-A2 (R.R. = 3.45, chi 2 = 14.93, Pc less than 0.002), Bw46 (R.R. = 6.47, chi 2 = 16.25, Pc less than 0.002), Cw11 (R.R. = 4.47, chi 2 = 9.19, Pc less than 0.04) and DRw8 (R.R. = 2.22, chi 2 = 5.62, P less than 0.03, Pc: n.s.) which form one of the typical HLA haplotypes in Japanese population due to the strong linkage disequilibria. On the other hand, the patients showed negative association with HLA-B7 (R.R. = 0.15, chi 2 = 7.15), Bw52 (R.R. = 0.24, chi 2 = 7.86), DR1 (R.R. = 0.07, chi 2 = 9.71) and DQw1 (R.R. = 0.45, chi 2 = 5.62), which form HLA-B7-DR1-DQw1 and Bw52-DR2-DQw1 haplotypes. Because HLA-A2 -Bw46-Cw11-DR9 haplotype was reported to be associated with Chinese Graves' patients, and because Bw46 showed the strongest association with the Japanese patients, it was suggested that HLA class 1 antigen, Bw46, might be the primary immunogenetic factor involved in the pathogenesis of Graves' disease. Since HLA-DQw6 was reported to be associated negatively with Hashimoto's thyroiditis as same as the current observation in Graves' disease, it was suggested that HLA-DQw6 may determine the resistance to autoimmune thyroiditis. The effect of HLA-DQw6 gene, therefore, on the experimental autoimmune murine thyroiditis (EAMT) was examined, using DQw6-transgenic mouse. F1 with C3H mouse, and backcross progeny between the F1 and C3H mouse which is a susceptible strain to EAMT. The measurement of anti-thyroglobulin antibody indicated that C3H mouse, (C3H x DQ-B6) F1 and backcross progeny between the F1 and C3H were high responders to the thyroglobulin, but that B6 mouse and DQ-B6 mouse were low responders. The histological examination of the thyroid gland of these mice failed to demonstrate the significant difference in susceptibility to EAMT among these mice. These results suggested that the immune response to the thyroglobulin was controlled by H-2k haplotype and that the effect of HLA-DQw6 gene on the immune response to thyroglobulin and on the autoimmune thyroiditis was marginal.     

Association of HLA-DRw9 with myasthenia gravis in Chinese

HLA phenotypes were studied in 59 Chinese myasthenia gravis (MG) patients. Unfractionated peripheral blood mononuclear cells were used for typing of HLA-A, B and C, and B-enriched lymphocytes for HLA-DR. Seventy-nine healthy subjects were included as controls. When compared with healthy controls, the patients showed significant increases in HLA-Bw46 (47.5% versus 14%, chi 2 = 18.7, P less than 0.001), HLA-DRw9 (59.3% versus 11%, chi 2 = 35.7, P less than 0.001), while HLA-DR3 was decreased (3.4% versus 32.9%, chi 2 = 18.2, P less than 0.001). Further analysis showed that the primary association was with DRw9 and the increase in Bw46 was secondary to it. Both HLA-Bw46 and -DRw9 were increased in all subgroups except where the age of onset was greater than 40 years. Finally, the HLA-A2-Bw46-DRw9 combination was also significantly increased in patients (25.4% versus 5.1%, chi 2 = 11.5, P less than 0.001), especially in the subgroups of MG with age of onset of less than 10 and males with age of onset of less than 40 years.     

The first example of an HLA-Bw45 antiserum produced in a HLA-Bw44 positive woman

An HLA-Bw45 serum (Mu46), which was produced by pregnancy in a Bw44 positive woman, is described. The serum was unable to be absorbed by Bw44 positive cells. Blocking tests employing broad B12 (Bw44 + Bw45) antisera, stimulated by either Bw44 or Bw45, showed that only F(ab)'2 from Bw45-stimulated B12 sera would completely block the cytotoxicity of this serum. It was concluded that Bw44 and Bw45 are distinct specificities which share common determinants. These findings are briefly discussed in relation to a recent report on the HLA-B antigen and supertypic Bw4, Bw6 antigen relationship.     

Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population

KIR and HLA loci are both highly polymorphic, and some HLA class 1 products bind and trigger cell-surface receptors specified by KIR genes. We examined whether KIR genes act in concert with HLA-B locus to control HIV-1 infection in a sample of Zambian patients. DNA samples from 88 Zambian patients with HIV-1 were examined. Patients were classified as either slow progressors (SP; n = 54) or rapid progressors (RP; n = 34) to AIDS. All were typed for HLA-B and KIR genes. Our results reveal an association between B*57 supertype (B*57s, which includes B*57 and B*58 alleles) and delayed progression to AIDS (p = 0.0007 by pc = 0.015; OR = 5.25). We also observed an increase incidence of Bw4-I80 in patients with slow progression (p = 0.001 by pc = 0.003, OR = 5). This increase was found to be secondary to B*57s. The presence of both KIR3DL1 and B*57S has a significant effect on progression to AIDS (p = 0.0008; OR = 5.61). B*57s genotypes with another HLA-B allele different from those in the trans position, which also had a specificity different to Bw4-I80 (Bw4-T80 or Bw6), was also greater in the SP than in the RP group (p = 0.00003; OR = 10.11). The presence of the inhibitory allele KIR3DL1 in combination with the HLA-B*57s alleles that contain the Bw4-I80 epitope, has a highly protective effect against progression to AIDS in Zambian patients.     

Immunogenetics of human American cutaneous leishmaniasis. Study of HLA haplotypes in 24 families from Venezuela

Twenty-four families with one or multiple cases of localized cutaneous leishmaniasis (LCL) from an endemic region with the highest incidence of LCL in Venezuela were typed from HLA-ABC, DR, DQ antigens and complement factors. The parental HLA haplotypes segregated at random among healthy and affected siblings but in backcross families significantly higher frequencies of HLA-A28 (p = 0.0018), -Bw22 (p = 0.0122), or -DQw8 (p = 0.0364) were present in affected compared to healthy siblings. HLA-B15 showed a higher frequency (p = 0.0062) among the latter group. Haplotypes Bw22CF31 (p = 0.0076) and Bw22DRw11DQw7 (p = 0.0163) were also significantly more frequent in affected compared to healthy siblings and A2Cw- (p = 0.0445) among the latter. No HLA genetic linkage with a putative LCL susceptibility gene(s) could be demonstrated in this study. A case/control comparison of 26 unrelated LCL patients (one proband from each family) and healthy individuals of the same ethnic origin confirmed the association of HLA-Bw22 (pc = 0.048) and -DQw3 (pc = 0.036) with LCL. The relative risk reached 12.5 for Bw22 and 4.25 for DQw3 with ethiologic factors of 0.17 and 0.64, respectively. HLA-DQw3 apparently makes the major contribution as a genetic risk factor for LCL at the population level.     

HLA-A and DPB1 loci confer susceptibility to Graves' disease.

To investigate HLA-linked genetic factors involved in the pathogenesis of Graves' disease, 76 patients and 317 healthy controls in the Japanese population were examined for HLA-A, B, C, DR, and DQ specificities by serologic typing and for HLA-DPB1 alleles by DNA typing by using the PCR-SSOP method. The frequencies of HLA-A2, B46, Cw11, and DPB1*0501 were increased and those of HLA-A24, B7, Bw52, and DR1 were decreased in the patients. The increased frequencies of HLA-A2 and DPB1*0501 in the patients were statistically significant when the corrected p value (pc) was applied (pc < 0.02 and pc < 0.002, respectively). ORs for a risk to develop the disease were calculated among individuals positive for DPB1*0501 and/or HLA-A2, and the highest OR (10.5) was observed in individuals possessed both DPB1*0501 and HLA-A2. This observation suggests a synergic involvement of a HLA class II allele (DPB1*0501) and an HLA class I allele (HLA-A2) in the pathogenesis of Graves' disease.     

HLA-A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin-dependent diabetes mellitus (IDDM)

The Basques were previously shown to present a high frequency of HLA—B18 and Bf Fl. which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA- A1, Bw57, Bf S, C4 FIS, DR7 and HLA- Aw30, Cw5, B18, Bf Fl, C4 Fs°, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA— DR3 : a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1. P < 10⁻¹¹). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%). and HLA—DR2 was not found. The silent allele C4 s ° was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P < 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.     

Inhibition of responder cell activity in mixed leukocyte culture reactions

An HLA-B7 antiserum showed cross-reactivity with HLA-B8, Bw41, a split of B40 (Bw60) and possibly Bw22 and B27, thus detecting one or more determinants on these antigens similar to an antigenic site on HLA-B7 usually not detected by other B7-antisera. The cross-reactions were demonstrable by adsorption of antibodies on lymphocytes followed by release at 37 degrees C, which enabled the detection of weak and otherwise hardly detectable reactivity. Released antibody molecules were detected in two different assays: (1) Antibody-dependent cellular cytotoxicity (ADCC) with HLA-B7 positive target cells (fluorochromasia micro ADCC). (2) Inhibition of MLC reactions with B7 positive stimulator cells. The B7-antibody, as detected in both assays, was released in decreasing activity from Bw41 greater than B8 greater than Bw60 much greater than B7 greater than (B27 = Bw22) positive cells. The order of sensitivity in which the various antigens were detected in ADCC assays in which the antiserum activity was measured directly on various target cells was different, viz. HLA-B7 greater than Bw60 = B27 greater than Bw41 greater than B8. Bw22 was not detected. Absorption studies demonstrated that HLA-B7 positive cells bound more B7 antibody activity than B8 positive cells. However, antibody molecules bound to B7 positive cells were mainly released as immune complexes, which could be dissociated by treatment with acid. In contrast, B7 antibody molecules bound to B8 positive cells were released as free antibody molecules. This marked difference in shedding properties further explained the previously described B7 specific unresponsiveness in MLC of HLA-B8 (and also Bw41) positive responder cells after sensitization with the B7 antiserum (de Rooij et al. 1980).     

HLA–DRw4 in Pemphigus Vulgaris Patients in Israel

Pemphigus vulgaris (PV) is relatively common in Jews. Three HLA antigens were significantly more frequent in 39 Israeli Jewish PV patients than in controls: A26 – 59% vs 20%; Bw38 – 61% vs 20%; and DRw4 – 90% vs 38%. The joint occurrence of A26–Bw38–DRw4 was observed in 46% of PV patients and in 10% of controls. Similar results were recently reported for Jews in the Los Angeles area. Yet, when our patient sample was grouped into Ashkenazi and non-Ashkenazi Jews, it was evident that each of the three antigens had a higher frequency both in Ashkenazi patients and controls as compared to non-Ashkenazim. The relative risk for DRw4 in Ashkenazim was 33.8 as compared to 14.4 in the total sample of Israeli PV patients. The phenotype A26–Bw38–DRw4 was present in 57% of Ashkenazi patients and in 13% of controls. Ashkenazi Jews have the highest prevalence of PV, and HLA associations were strongest with Ashkenazi PV patients. These associations were with three antigens, all of high frequency in that group.     

HLA Antigens of Platelets. IV. Influence of "Private" HLA-B Locus Specificities on the Expression of Bw4 and Bw6 on Human Platelets

Quantities of the HLA-B antigens B5, B7, B8, B13, B27, and Bw44 were determined on platelets of subjects heterozygous for those markers using an assay based on inhibition of antibody-mediated ⁵¹Cr release from lymphocytes. In confirmation of previous studies, Bw44 was found to vary about 35-fold and B8 about 8-fold. In contrast, B5, B7, B27, and B13 varied only 2–3-fold. Expression of each of the six antigens was proportional to that of its associated broad specificity, Bw4 or Bw6. The antigens Bw4 and Bw6, when measured directly on platelets of 62 normal heterozygous subjects, were found to vary 32-fold and 20-fold, respectively. Bw4 was strongly expressed on platelets carrying B5 or B27 (P > 0.001), was weakly expressed in the presence of B13 (P > 0.001) and was variable, possibly bimodal, in the presence of Bw44. Bw6 was strongly expressed on platelets carrying B7, Bw15.1, or Bw35 (P > 0.01) but was weak on platelets carrying B8 or B14 (P > 0.01). Little or no variation in Bw4 or Bw6 was observed on lymphocytes of the same donor population. These findings are consistent with the possibility that private HLA-B locus specificities influence the expression of part or all of the HLA-B molecule on the platelet surface through an undetermined mechanism. The atypical behavior of Bw44/Bw4 on platelets suggests the possibility that Bw44 consists of two subspecificities not yet detectable with available serologic reagents. Variability of HLA markers in tissues other than platelets could have important immunobiologic implications which seem deserving of further investigation.     

The HLA-B12 and -B40 cross-reactive groups and their serological relationships

The serological analysis of 82 broad HLA-B antisera, produced by pregnancy alone, containing reactivity against HLA-B 12 and/or B40 positive cells and up to nine additional specificities was performed, using highly selected lymphocyte panels. The HLA typing of 76 of the antiserum donors and 75 of their husbands showed that the antisera were stimulated in response to one of 10 different HLA-B antigens. It also showed the influence of serum donor HLA-B antigens on the reaction range of the antiserum produced, as well as significant HLA-B antigen frequency disturbances within varous groups of the antiserum donors. Fifteen HLA-B specificities were found to comprise the B12 cross-reactive group and its related cross-reactions, with bidirectional cross-reactivity occurring between Bw44, Bw45, Bw49 and Bw50 (unidirectional between Bw44 and Bw50). Seventeen specificities were observed in the B40 cross-reactive group and its related crossreactions, with bidirectional cross-reactivity occurring between Bw41, Bw50, Bw60 and Bw61. Antisera were studied that showed: (1) cross-reactivity between Bw44, Bw45 and Bw60 stimulated antisera and both subdivisions of the B12 and B40 antigens; (2) cross-reactivity between B13, Bw44, Bw49, Bw60 and Bw61 stimulated antisera and Bw47; and (3) cross-reactivity between Bw44, Bw49, Bw60 and Bw61 stimulated antisera and B13, with bidirectional cross-reactivity occurring between B13, Bw60 and Bw61 and between B13 and Bw44. Bidirectional crossreactivity was also observed between B37 and Bw44 and between B7 and Bw60. HLA-Bw48 was shown to be included within the reaction range of both B7 and Bw60 stimulated antisera. Preferential cross-reactivity with one of two antigen subdivisions was extensively observed and occurred exclusively between antigens of the same Bw4/Bw6 association as the antiserum stimulating specificity. The results are discussed within the framework of the existence of multiple shared antigenic determinants.     

在中国人中检出HLA-B15的一个新分解物SH7

使用第 9届国际组织相容性专题讨论会血清,在中国人中发现 B15的一个新反应格局,我们暂称为 SH7。在18个家庭中,有4个家庭带有 SH7并在孩子中表现出分离。来自中国人群的血清 460以及第 9届会议血清 9w179、9w180、9w277、9w278 含有 Bw62和 SH7。SH7似乎是介于Bw35和B15之间的中间抗原,它能够与Bw62、Bw35以及Bw53区别,并在它们存在时被检出。结果证明了B15是一个远比现在分解为Bw62和Bw63更为复杂的复合体。     

Identification of a novel allele HLA-B*7805 in a Japanese female

A new HLA-B*78 allele, B*7805, was identified in a healthy Japanese female. The results of her serological HLA class I typing showed an unusual Bw4/Bw6 pattern with strongly positive reactivity to anti-Bw6, i.e. A24, -, B52, -, Bw4, Bw6. In DNA typing, she was typed as A*24, -, B*52, B*78-like, Cw1202, -, (Bw4, Bw6). Cloning and sequencing of exon 2 and exon 3 of her B locus genes revealed a new allele B*7805. The cloned B*7805 differed from B*78021 by three nucleotide substitutions in exon 2 at position 259 (A to G), 261 (C to G) and 272 (A to C), and contained sequences defining Bw6 motif in the region of codon 77 to 83.     

HLA-DR4 associated Dw types in rheumatoid arthritis

Frequencies of HLA-DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n = 57) compared to 31.2% in normal controls (n = 96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p less than 0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p less than 0.001) in the index cases. A non-significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p less than 0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA-B antigens and DR4/Dw types to be made. HLA-Dw4 was predominantly found with B44 and Bw62 with nearly all DR4/Bw62 haplotypes being Dw4 positive. HLA-Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data. Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and "complotype". However, there was a suggestion of C4A3. BQO being associated with Dw4 (34.2% vs 16.1% X2 = 2.9 p = ns) and C4A3, B1 with Dw14 (45.5% vs 27.6% X2 = 2.1 p = ns).(ABSTRACT TRUNCATED AT 250 WORDS)     

Human leucocyte antigen‐Bw4 and Gag‐specific T cell responses are associated with slow disease progression in HIV‐1B‐infected anti‐retroviral therapy‐naive Chinese

In China, the majority of human immunodeficiency virus (HIV) infections are predominately subtype B. It is important to characterize the HIV‐1 subtype B‐specific and its T cell response within the Chinese population, with the aim of identifying protective correlates of immunity to control HIV‐1 infections. In this study, we performed a comprehensive analysis looking into the magnitude/strength of T cell responses directed at the Gag protein of the HIV‐1 subtype B, one of the most conserved HIV‐1 proteins. The study group consisted of anti‐retroviral native and chronic HIV‐1 subtype B‐infected individuals. We used enzyme‐linked immunospot (ELISPOT) assay to quantify the total T cell responses to HIV‐1 Gag at the single peptide level. Twenty‐eight (38%) peptides were recognized in 24 (82·8%) individuals. The p24 was identified as the most frequently recognized subunit protein with the greatest T cell response in the test, which correlated positively with CD4⁺ T cell count and inversely with viral load (VL). At the level of the human leucocyte antigen (HLA) supertypes, we detected the highest levels and a significant correlation with both the CD4⁺ T cell count and the VL with Gag T cell responses in Bw4/Bw4. These findings demonstrate that (i) the HIV‐1B Gag p24‐specific immune responses play an important role in controlling viral replication and slowing clinical progression; and (ii) HLA‐Bw4/Bw4 allele has stronger T cell responses, which is associated with slow clinical progression in Chinese HIV patients.     

HLA Bw57 and DR7 association with psoriasis vulgaris in south India

Eighty-three south Indian patients with psoriasis vulgaris were studied for HLA antigen frequencies and compared with 77 controls studied simultaneously. HLA Bw57, a split of B17 was found elevated in the patients. The two sexes differed in their age-at-onset curves: females had a preponderance to early onset of the disease, while the males had late onset. Among these patients, major group 3, a Western Brachycephal Armenoid group, revealed the highest risk for B17 & Bw57 but not major group 2, a Mediterranean one.     

A F(ab'')2 fragment blocking study of the HLA-B14 antigen

The HLA-B14 antigen exists in two serologically distinct forms termed Bw64 and Bw65. These two B14 subgroups were studied using the ability of F(ab')2 fragments from HLA-B14 and Bw6 antisera to block the binding of cytotoxic HLA antibodies directed towards the same or an adjacent antigenic site. The findings suggest that the B14 antigen consists of several antigenic determinants some of which are spatially distinct and others which are closely associated. A "common" determinant possessed by both B14 subtypes is proposed which is separate from a Bw64 (or Bw65) site. Additional determinants that B14 shares with B8, B18 and B38/B39 appear to be distinct from the Bw64/Bw65 site, variably associated with the B14 "common" determinant but closely adjoining the Bw6 antigen.     

Genetic profile of KIR and HLA in southern Chinese Han population

KIR and their HLA ligands are encoded by two of the most diverse gene families in the human genome. The function of KIR on the NK cell is highly dependent on the normal expression of class I HLA on the target cell. Previous population studies in southern Chinese have been focused on the KIR framework genes and genotypes but little is known about the compound profiles of KIR/HLA. The present study examined 503 unrelated individuals from southern Chinese Han population for the polymorphism of KIR and class I HLA genes. All 16 KIR genes were detected in the study population and the four framework genes KIR3DL2, 3DL3, 3DP1, and 2DL4 were present in all individuals. Thirty unique KIR gene profiles were found reflecting a rather limited number of KIR haplotypes in this population. KIRAA1 was the most common profile observed in 54.7% of the samples. Among the AA1 individuals, 15.6% were homozygous for the deleted KIR2DS4. Haplotype A (74.8%) was more common than haplotype B (25.2%). HLA-C1 was a much more common ligand for 2D KIRs than C2. Bw4-80I, Bw4-80T, and the Bw4-bearing HLA-A alleles were detected at similar frequencies. The matched KIR+HLA pairs 2DL2/3+C1 (98.1%), 3DL1+Bw4 (73.3%), 3DL2+A3/11 (60.0%) were the most common ones whereas 3DS1+Bw4-80I was the least common (9.4%). A total of 193 unique compound profiles of KIR–HLA were identified in 480 informative individuals, 130 of the profiles being detected only once. The study provided a comprehensive analysis of the KIR/HLA profiles in southern Chinese in regards of the presence/absence of KIR genes, HLA ligands, matched KIR+HLA pairs, and KIR/HLA compound profiles. The results could help to better understand the role played by KIR/HLA interaction in associated diseases and clinical transplantation in southern Chinese.     

Unexpected Bw4 and Bw6 reactivity patterns in new alleles

The Bw4 and Bw6 epitopes were the first HLA-B differences to be recognized by serological methods. Since then 44 serological groups have been identified and more than 250 alleles assigned by molecular typing methods. In general each serological HLA-B group is associated with the presence of either the Bw4 or the Bw6 epitope. There are several exceptions to this rule. Four alleles, B*4601, *7301, *5503 and *1806, show no serological reactivity with either Bw4 or Bw6. Although the Bw6 motif at residues 77-83 is present in these alleles the Bw6 epitope is modified by a valine at residue 76. One or more alleles from the B8, B40 and B62 groups are identified as Bw4 positive, whereas all others are Bw6 positive. In the groups B27, B44 and B47 several alleles are found to be Bw6 positive, while the majority is Bw4 positive. Histocompatibility testing of dialysis patients and their families revealed the serological presence of an unexpected Bw4 epitope associated with B18 in one patient and B56 in another. Allele-specific amplification and sequencing of exons 2 and 3 of these HLA-B alleles revealed the presence of the Bw4 sequence motif for both. The new alleles were assigned B*1809 and B*5607, respectively. In 2 other patients the presence of a new B*07 allele was determined by sequence based typing. Although the new allele, B*0715, showed the Bw6 sequence motif at positions 77 to 83, a substitution of amino acid 76 from glutamic acid to valine was identified. This change resulted in an aberrant Bw6 serological reaction pattern.