摘要:

Mapping the MHC‐associated susceptibility and resistance factors for insulin‐dependent diabetes mellitus (IDDM) has been difficult due to the strong linkage disequilibrium within the HLA‐DR‐DQ region. Previous analyses have suggested that the study of IDDM‐associated haplotypes in different races might be useful for identifying the responsible genes. We have performed complete HLA class II genotyping to study susceptibility and resistance to IDDM in 34 randomly selected African‐American IDDM patients and 69 ethnically‐matched controls. IDDM patients showed highly significant increases of DRB1*0301, DRB1*0401, DRB1*0405, DQA1*0301, DQA1*0302, DQB1*0201 and DQB1*0302. Analysis of DQA1‐DQB1 associations showed that DQA1*03 combined with both DQB1*0201 and DQB1*0302 gave the highest odds ratio, suggesting a synergistic effect due to formation of heterodimers encoded both in cis and in trans. Among the subsets of DR4, only DRB1*0401 and DRB1*0405 were increased in diabetic patients. Interestingly, DQB1*0602 and DQB1*0301, which have previously been thought to encode resistance factors in Caucasians, were not significantly decreased and, after removal of known susceptibility haplotypes, were found to have essentially identical frequencies in patien

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01980.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

A series of 10 normal cervix epithelia, 38 condylomas, 17 CIN (cervical intraepithelial neoplasm) I/II (low‐grade CIN), 10 CIN III (high‐grade CIN), 27 squamous cell carcinomas and 7 adenocarcinomas of the cervix were studied in paraffin‐embedded sections for the expression of MHC class I antigens, using antibodies against HLA antigens and the immunoperoxidase technique. A PCR technique was also used to evaluate the presence of HPV‐16 DNA. All samples from normal tissue, benign, premalignant and CIN III lesions expressed HLA class I antigens. However, 15% of the invasive carcinomas completely lacked HLA‐B and HLA‐C antigen expression, 20% presented a heterogeneous pattern and 2 cases lacked HLA‐B and HLA‐C heavy chain but retained β,‐microglobulin. MHC class I antigen expression on tumors was compared with clinicalpathological parameters. The absence of expression of HLA class I molecules was significantly associated with the Glanz histoprognostic index of malignancy. HPV‐16 sequences were detected in 60% of the condylomas, 88% of the CIN I/II, 80% of the CIN III and 82% of the cervical carcinomas. Eight‐six per cent of the tumors expressing HLA class I antigen presented HPV‐16, whereas only 40% of the nonexpressing tumors did. Our results lead us to the following conclusions: a) HLA class I losses occurred when the tumor became invasive, and in tumors of a more aggressive histological type; b) The presence of HPV‐16 was associated with tumors expre

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01981.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The HLA‐A10 crossreacting group consists of the A25, A26, A34, A43 and A66 antigens. Here, we report allelic sequences for A43 and for 2 subtypes of both A26 and A34. Combining these results with previously determined sequences for A25, A26 and A66 enables molecular comparison of all the serologically defined A10 antigens. They form a closely related and well‐defined group of alleles which may have originated with A*2601. Patterns of serological crossreactivity are correlated with sequence and a public epitope shared by A33 and members of the A10 family is localized to residues R62 and N63. The A*2501, A*4301 and A*6601 alleles appear to have derived from A*2601 by single gene conversion events with other HLA‐A alleles. In the case of A*4301, the donor allele was probably an A29 allele as A*4301 has a small element of sequence in the α1helix (residues L62 and Q63) uniquely shared with A29. The chimaeric structure of A43 explains the reactivity of A43 molecules with both A10 and A29 alloantisera. The rare Oriental variant of A26 (A26v*) is encoded by an allele (A*2602) that differs from A*2601 by a unique nucleotide substitution which changes aspartate to asparagine at position 116 in the floor of the peptide binding groove. Thus A*2602 is a functionally distinct allele that originated by a point mutation. Alleles encoding A34 and A66 antigens are found to have very similar structures, explaining the difficulty in their serological definition. Further illustration of serological difficulties in discriminating the antigens of the A10 group is the finding that the A26.2 electrophoretic variant of A26 is identical in structure to

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01982.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

TrJ1 is a cytotoxic human hybridoma mAb (IgMλ). Its reaction pattern with a panel of 42 HLA‐defined lymphoblastoid B‐cell lines correlated precisely with expression of DQ2. By flow cytometry it was shown that the binding of TrJ1 to DQ2 was efficiently blocked by the murine anti‐DQ2 mAb 358.4, indicating that the TrJ1 and 358.4 epitopes overlap. TrJ1 reacted much better with EBV‐transformed B cells than with B cells freshly isolated from blood. TrJ1 seemed suitable for typing freshly isolated B cells provided the incubation with complement lasted for 115 min in Terasaki plates. One or more of the DQ2‐specific polymorphic amino acids E46, F52, L52, L55, K74or A74, situated on the α‐helix of the DQ2 β chain, are probably critical for th

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01983.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

A double‐blind study was carried out to evaluate the relative performance and reliability of the PCR/SSOP assay compared to conventional serological typing in identifying HLA‐DR alleles. A total of 268 consecutive samples were entered into the study. In 14 (5.2%) of the cases, HLA‐DR serology could not be performed due to poor cell viability, while in seven (2.6%) of the cases, PCR/SSOP typing could not be performed due to poor amplification or to contamination with exogenous DNA. Among samples that were successfully typed by both methods, serologic typing correctly identified 455/465 (97.9%) DR antigens, while PCR/SSOP correctly identified 464/465 (99.8%) DR alleles (p = 0.0117, McNemar's test). The majority of discrepancies in serologic typing resulted from a lack of discriminative alloantisera to identify DR6 or DR103. For the overall sample set (N = 268), serology provided accurate results in 244 (91.0%) cases, while PCR/SSOP provided accurate results in 260 (97.0%) cases (p = 0.0037). The results of this study demonstrate that PCR/SSOP typing for HLA‐DRB1 alleles provides results that are equal to or surpass serological typing for HLA‐DR antigens. In addition, the PCR/SSOP approach offers the advantages of better reagent availability, lower cost, more rapid turn‐around time, and greater accuracy, all of which would warrant its use as an HLA typing metho

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01984.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01985.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01986.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01987.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01988.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1993.tb01989.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY