A strong association between HLA-B*5101 and Behçet's disease in Greek patients

Behçet's disease is known to be associated with HLA-B51, one of the split antigens of HLA-B5, among many different ethnic groups. In a Greek population, an increased incidence of HLA-B5 in the patient group also been reported. Because the B51 antigen has been recently identified to comprise seven alleles, B*5101-B*5107, we performed HLA-B51 allele genotyping by the PCR-SSP method as well as serological HLA-A and -B typing among 31 Greek patients with Behçet's disease to investigate whether there is any correlation between one particular B51-associated allele and Behçet's disease. The frequency of B51 was remarkably high (80.6%) in the patient group as compared to the ethnically matched control group (26.7%). In addition, HLA-A26 was also increased in the patients (29.0%) as compared with the healthy controls (3.3%). B51 allele genotyping revealed that all these B51-positive patients carried B*5101. This study revealed a strong association of Behçet's disease in Greeks with one of B51 subantigens, providing insight into the molecular mechanism underlying an HLA association with Behçet's disease.     

Characterization of a novel HLA-Cw*02 variant, Cw*0208, in a Caucasian individual

We describe an additional HLA-Cw*02 variant, HLA-Cw*0208, which has been identified in a renal transplant recipient of Caucasian origin (Italy). After performing preliminary serological typing, we analyzed exons 2 and 3 of the HLA-C locus polymorphism by cloning the amplified DNA and using a sequence-based typing method. The new allele differs from Cw*020202 by one nucleotide substitution at nucleotide 61 (G-->A) of exon 2, which translates to a difference of one amino acid at residue 21 (His-->Arg) of the HLA-C heavy chain. We propose that Cw*0208 was generated by a random point mutation in codon 21 from the Cw*020202 allele, or through gene conversion of Cw*020202 with another allele, probably the Cw*1205 and Cw*1602 alleles.     

Identification of an HLA-C variant allele, Cw*0805, by sequencing based typing

Abstract: We have identified a. variant HLA-C allele, Cw*0805, in DNA isolated from a blood sample used in the UK National External Quality Assessment Scheme for Histocompatibility and Immunogenetics. The DNA was initially typed by PCR-SSP and PCR-SBT as Cw*0802, 1602 with a single mismatch in exon 2 of one of the alleles. The two HLA-C alleles were separated by locus- and allele-speciflc PCRs and sequencing analysis showed that the Cw*0802 allele was variant in this sample, with a single mismatch in exon 2 at position 289.     

HLA and tumour necrosis factor (TNF) polymorphisms in ocular Behçet's disease

The role of HLA-B*51 and other major histocompatibility complex (MHC) genes in Beh?et's disease (BD) remains unknown. We have performed HLA and tumour necrosis factor (TNF) polymorphism analysis in BD and evaluated their contribution to ocular disease. In this study, 102 patients and 115 controls of Middle Eastern descent were investigated by HLA and B*51 subtyping using novel primers, and by LT alpha NCo 1 and TNF 308 promoter polymorphism analysis. The frequency of the HLA-B*51 family of alleles was raised in patients compared to controls (66% vs. 15%, Pc=2.5x10(-12), OR=10.9). The odds ratio (OR) of this group of alleles for subgroups of patients was as follows: non-ocular patients 7.8, all ocular patients 12.6, blind patients >22. HLA-B*51 subtyping detected B*5101, 07, 08 and 09 alleles, with a similar frequency among patients and controls. HLA-Cw*1602 was associated with B*5108, but was not an independent risk factor for disease. The LT alpha (TNFB*2) allele was associated with HLA-B*51 among patients and the frequency of this allele was significantly higher among completely blind patients compared to both non-ocular patients (P=0.048, OR >3.6) and to healthy controls (P=0.022, OR >4.3). The rare TNF-2 polymorphism at the TNF -308 promoter position was associated with HLA-B*50 (not B*51), and was not associated with BD. Thus, in this population the HLA*B51 family of alleles is a strong risk factor for BD, and in particular the development of ocular disease. HLA-B*51 subtyping did not define new markers for BD. A primary role for TNF gne polymorphisms in BD was not identified, but co-expression of the TNFB*2 allele with HLA-B*51 may contribute to severity of ocular disease.     

Behçet's disease: the first Mongolian case in literature showing HLA B51, MICA gene type *5/*6

Beh?et's disease is a chronic multi-systemic disease of unknown origin that includes mucocutaneous, ocular, cardiac, vascular, renal, gastrointestinal, neurologic and cutaneous involvement. The disease is spread throughout the world, but it is most prevalent in the eastern Mediterranean region-along the Silk Road-, and in Japan, China, and Korea. Recently, we treated a Mongolian patient who had complete-type Beh?et's disease. As far as we know, this case is the first report of a Mongolian with Beh?et's disease in the English literature. HLA typing in this patient revealed A2, A24;B51, B35; Cw4, Cw7; DR9, DR11. Study of the MICA genetype showed *5, *6 positive. Our data provided adequate evidence, from an epidemiological aspect, to support the belief that Beh?et's disease is most prevalent along the old Silk Road.     

HLA-B*51 allele analysis by the PCR-SBT method and a strong association of HLA-B*5101 with Japanese patients with Behçet's disease

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

Association of HLA-B 51 subtypes and Behcet's disease in Spain

Abstract: We have studied the distribution of the different HLA-B51* al-leles among patients with Behçet's disease (BD) and ethnically matched healthy controls in a Spanish population. The serological B51 specificity was increased in BD patients (37.5% versus 15.5% in controls). Among the B51-assodated alleles, the frequencies of B*5101 (32%) and 5108 (5.5%) were increased in BD patients with respect to the control frequencies (13% and 1.2% respectively). The fact that different HLA-B51 subtypes are associated with BD could suggest that common motifs shared by HLA-B51-related alleles are involved in the susceptibility to BD or, in the light of recent studies, that a mutation causing the susceptibility to BD occurred in the B*5101 haplotype, close to HLA-B gene, before the divergence of B*5108 from the B*5101 allele.     

Four-digit allele genotyping of the HLA-A and HLA-B genes in Japanese patients with Behcet's disease by a PCR-SSOP-Luminex method

The present study represents the first four-digit allele genotyping of HLA-A and -B in Japanese Behcet's disease (BD) patients and controls using a new genotyping method (named the PCR-SSOP-Luminex method) to determine the association of certain HLA-A or -B alleles with BD. Peripheral blood lymphocytes were collected from 180 Japanese BD patients and 170 healthy controls. The genotype frequency of HLA-B*5101 was significantly increased in the patients (61.7%) as compared with the controls (15.9%) (Pc = 1 x 10(-16), OR = 8.5). When we recalculated the phenotype frequencies after excluding the HLA-B*51-positive patients and controls to account for the effects of the linkage disequilibrium and the abundance of the HLA-B*51 allele, the frequencies of HLA-A*2602 and HLA-B*3901 had a weak association in the patient group without HLA-B*51 as compared with the control group without HLA-B*51 (A*2602; Pc = 0.130, OR = 4.3, B*3901; Pc = 0.099, OR = 3.5). This study confirmed on the basis of using a new and more accurate genotyping method that Japanese BD patients have a strong primary association with HLA-B*5101. The significant increase of HLA-A*2602 and B*3901 in the patient group without HLA-B*51 suggests that these two alleles might also have some secondary influence on the onset of BD.     

Significant associations of HLA-B*5101 and B*5108, and lack of association of class II alleles with Behçet's disease in Italian patients

Beh?et's disease has been known to be strongly associated with human leukocyte antigen (HLA) B51, one of the split antigens of HLA-B5. An increased incidence of HLA-B51 in the patient group has also been reported in an Italian population. Since the B51 antigen has been recently identified to comprise nine alleles, B*5101-B*5109, we performed HLA-B51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method as well as serological HLA-A and -B typing among 21 Italian patients with Beh?et's disease in order to investigate whether there is any correlation of one particular B51-associated allele with Behcet's disease. In addition, HLA class II genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. As a result, only the phenotype frequency of the B51 antigen was found to be significantly increased in the patient group as compared to the ethnically matched control group by the corrected P-value analysis (71.4% in patients vs. 17.9% in controls; chi2 = 14.26, Pc = 0.0042, R.R. = 11.5). In the B51 allele genotyping, 11 out of 15 B51-positive patients were B*5101 and the remaining four were B*5108, whereas all of 5 normal controls were B*5101, showing significant association of each allele with Beh?et's disease. No significant difference was observed between the patient and control groups in the HLA class II allelic distribution. This study revealed a strong association of Beh?et's disease in Italian with B*5108 as well as B*5101, providing important insight into the molecular mechanism underlying an HLA association with Beh?et's disease.     

A new pair of HLA-C alleles, Cw* 12042 and Cw*1203, differing at the KIR-related dimorphism of codons 77–80

Abstract: A previously unknown HLA-C variant of the Cw*12 group was identified by PCR-SSP from genomic DNA of cell NDS-JD. Molecular cloning and nucleotide sequence analysis permitted the characterization of the complete coding region of this new allele, Cw*12042. The new variant differs from the recently reported Cw*12041 by two silent changes at exons 2 and 3, and from Cw*1203 by coding changes at codons 77 and 80. Cw*1203 (Ser-Asn) and Cw*12042 (Asn-Lys) constitute the second known example of HLA-C alleles only differing at the KIR-related dimorphism of residues 77–80. The new allele is associated in cell NDS-JD with the haplotype HLA-A*2403, Cw*12042, B*51, DRB1*1502, DRB5*0102, DQB1*0601, possibly related from the evolutionary aspect to the ancestral haplotype A*2402, Cw*1202, B*5201, DRB1*1502, DRB5*0102, DQBl*0601.     

Neuronal Hyaline Inclusions Observed in an Autopsy Case of Behçet's Disease

An autopsy case of Behçet's disease is reported. The patient, a 59 year old Japanese woman, died of intestinal bleeding after a 34 year clinical course of Behçet's disease. She also suffered from recurrent oral aphthous ulcers, erythema nodosum like cutaneous lesions and genital ulcerated lesions. Autopsy revealed marked atherosclerosis of the aorta and multiple deep ulcerations in the terminal ileum with no significant vascular lesions. Lewy bodies and globular hyaline inclusions in the neurons of the central nervous system were noted, although there were no clinical symptoms of Parkinson's disease throughout the clinical course. These findings appear to suggest that the patient was probably in the preclinical or early stage of Parkinson's disease. However, the presence of Lewy bodies in the 6th decade without any accompanying symptoms is very rare. This case seems to draw attention to the presence of these neuronal inclusions in Behçet's disease.     

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.     

HLA-C typing of eleven Papua New Guineans: identification of an HLA-Cw4/Cw2 hybrid allele

HLA-C polymorphism of 11 individuals from Papua New Guinea was studied by serology and DNA typing (SSP ARMS-PCR). To resolve certain discrepancies HLA-C alleles were cloned and sequenced. Five alleles were identified by sequencing, four of which; Cw*0304, Cw*0401, Cw*12022 and Cw*1502 have been identified previously in other populations. The fifth allele, which was found in four individuals is a novel HLA-C allele. The new allele, called HLA-Cw*0403 is most similar to HLA-Cw*0401, differing by 10 nucleotides, 9 of which are located in the region from nucleotide 98 to 218. This region of Cw*0403 is identical to both HLA-Cw*0201 and Cw*02022. The 9 nucleotide differences between Cw*0401 and Cw*0403 result in 6 amino acid differences in the α1 domain. These amino acids in Cw*0403 may contribute to the serological typing of some, but not all Cw*0403 expressing cells. The Final difference between Cw*0401 and Cw*0403 is a coding substitution at nucleotide 979 in exon 5. The guanine found in Cw*0403 is identical to all HLA-C alleles except HLA-Cw*0401, which has an adenine. The Cw*0403 allele was most likely formed by a gene conversion event between Cw*02 and Cw*04, involving a minimum of 121 to a maximum of 215 nucleotides.     

HLA-A*020115 and HLA-Cw*030203 show new synonymous mutations in exon 4

Two novel human leukocyte antigen (HLA) class I alleles, A*020115 and Cw*030203, were completely characterized by sequencing-based typing. Both present synonymous new HLA polymorphisms at exon 4. A*020115 shows a single nucleotide change regarding A*02010101 at codon 245 GCG > GCC). In contrast, Cw*030203 differs from Cw*030202 in a point mutation at codon 271 (ACC > ACT).     

Six new HLA class I alleles detected by PCR-SSO genotyping

This paper describes six new alleles; A*0240, A*2614, B*3924, B*4425, Cw*0807 and Cw*12023, which were discovered during routine genotyping with sequence specific oligonucleotides (SSO's). Five of the new alleles have changes in residues which belong to the antigen binding site of the HLA protein. These new variants may have altered antigen binding properties and may cause differential immunological responses that could affect transplantation outcome1.     

HLA-B*27 allele associated to Behçet's disease and to anterior uveitis in Moroccan patients

Human leukocyte antigen HLA-B51 is the most strongly associated gene with Beh?et disease (BD) in different ethnic populations. We analyze the influence of HLA-B alleles in BD predisposition in Moroccan population and its association with clinical manifestations. The HLA-B phenotype frequencies were analyzed by serologic HLA class I typing and by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) reverse dot blot hybridization in 120 unrelated Moroccan patients: all of whom fulfilled the international study group criteria for Beh?et's disease, and in 112 ethnically matched healthy controls. Besides HLA-B*51 allele (20%), a significant increased frequency of the HLA-B*27 allele was found in Moroccans patients with Beh?et's disease when compared to controls (13.3% of patients versus 2.7% of controls, chi square =?8.75, OR =?5.59, 95% IC [1.58-19.75] and particularly in the patients who presented an anterior uveitis (25% vs. 5.5%, p 相似文献   

Sequencing based typing for HLA-C. Identification of three new alleles: Cw*0307, Cw*0502 and Cw*0504

HLA-C has been described as a transplantation locus in the unrelated bone marrow transplantation setting, and noticeably the number of mismatches between HLA-A,-B,-DRB1 compatible pairs is considerably high. Sequencing based typing (SBT) is an accurate and efficient methodology utilised in the HLA class I and II allele level of resolution. SBT for HLA-C locus was applied on a sample of 40 HLA-A,B,DRB1,DRB3/4/5,DQB1-compatible bone marrow recipient-donor pairs, and 3 new HLA-C alleles have been found. Cw*0307, well defined by serology as Cw3, showed two amino acid changes at the NK motif 77-80 regarding all described Cw*03 alleles, N77K80 instead of S77N80. Two new Cw*05 alleles were described, Cw*0502 properly typed by serology, and Cw*0504 that behaves as a short antigen. Cw*0502 differed from Cw*0501 by only one nucleotide at exon 3, that generated an amino acid replacement at codon 177, K to E. Cw*0504 differs from Cw*0501 by two clustered amino acid positions (114 and 116) placed at the peptide binding site. The rate of new HLA-C alleles found in this small series evidences a high grade of hidden HLA-C diversity in the Spanish population, particularly in the well-defined serologic specificities.     

The association between HLA class II haplotype with Graves' disease in Thai population

The distribution of HLA-DRB1, -DQA1 and -DQB1 alleles were analysed in 124 Graves' disease (GD) patients compared to 124 normal controls in order to identify the alleles/haplotypes associated with GD in Thai population. The DRB1*1602-DQA1*0102-DQB1*0502 haplotype was significantly increased in GD patients (P = 0.0209, OR = 2.55). DRB1*07-DQA1*0201-DQB1*0201 haplotype (P = 0.039, OR = 0.32) and HLA-DRB1*12-DQA1*0601-DQB1*0301 haplotype (P = 0.0025, OR = 0.28) were significantly decreased in GD patients. Interestingly, a protective DRB1*07 allele in Thai population lacks an arginine at position 74 similar to DRB1*0311 (a protective allele in Caucasians). A significant association of DRB1*1602-DQA1*0102-DQB1*0502 and HLA-DRB1*12-DQA1*0601-DQB1*0301 alleles and haplotypes with GD was recently reported in Korean but not in any Caucasian studies. Thus, DRB1*1602 allele and closely linked haplotype, DRB1*1602-DQA1*0102-DQB1*0502, might serve as a marker for genetic susceptibility to GD in Asian population.     

Sequence-based typing characterization of the novel HLA-Cw*1609 allele in the Moroccan Chaouya group

The novel human leukocyte antigen (HLA)-Cw*1609 allele was identified by sequence-based typing in a Moroccan Chaouya donor. It differs from the closest Cw*1602 by only one nucleotide (C --> G) at position 244 in exon 2 (Glu to Gln at codon 58 in alpha1 domain).     

Characterization of a novel HLA-Cw*04 variant in a Laotian family: HLA-Cw*0406

The sequence of a new HLA-Cw*04 allele has been identified in a Laotian family. This allele, designated Cw*0406, differs from Cw*0403 by a single nucleotide substitution at codon 156 (CGG-->CTG) in the alpha2 domain, leading to an amino acid change from Arginine to Leucine. Further screening by specific amplification of two ethnically different populations, i.e. French (n=150) and Lebanese (n=100), provided no case of Cw*406, suggesting that the distribution of this allele may be restricted.