ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01670.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The effect ofin vitroadministration of Cyclosporin A (CsA) during mitogen, antigen and alloantigen activation of human T‐lymphocytes on high affinity interleukin‐2 (IL‐2) receptor expression and ‐turnover and IL‐2 production was investigated. The presence of CsA reduced3H‐thymidine incorporation and binding of radiolabeled human recombinant (ala125) IL‐2 to high‐affinity receptors in a dose‐dependent fashion, although a pronounced inter‐ and intra‐individual variation in sensitivity to CsA mediated immunosuppression was observed. Maximum inhibition was obtained when antigen and CsA were added to culture medium simultaneously. Preincubation with CsA did not influence the response. Although the number of IL‐2 receptors was reduced, the turnover of the remaining high affinity IL‐2 receptors on CsA treated cells was unaffected. Thus, binding, internalization and degradation were qualitatively unaltered by CsA administration. Finally, T cell activation in the presence of CsA reduced radioimmuno detectable IL‐2 in cell culture supematants to about 20%. CsA, added during antigen activation, reduced the number of Tac antigen presenting cells, but anti‐Tac was unable to detect variations in the expression of high affinity IL‐2 receptors. The present data indicate that CsA mediates immunosuppression by affecting early events during T‐cell activation, and that variations in high affinity IL‐2 receptor expression and IL‐2 produ

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01671.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Inheritance of parental HLA haplotypes was examined in the offspring of 95 multicase rheumatoid arthritis (RA) families. Overall, in these families there was no evidence of preferential transmission of one parental haplotype, although this might have been expected given the loading of these families with RA cases. However, there was a difference in inheritance when the affected and non‐affected offspring were compared. A co‐segregation analysis showed that the inheritance of parental HLA haplotypes was different between the affected and the unaffected offspring. Unlike a previous report, no difference was demonstrated in this study between the offspring of affected and non‐affected parents. Similarly, the affected offspring of HLA DR4 heterozygote parents were more likely to inherit HLA DR4 than the non‐affected offspring. It is concluded first that linkage studies of RA using the affected sib‐pair method are not invalidated, which would have been the case in the presence of preferential transmission of HLA to all offspring. Secondly, HLA and specifically HLA‐DR4 does co‐segregate with RA, and, finally, parental RA status, independent of DR4, has little influence in explaining the genetic suscept

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01672.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

We have compared haplotypes bearing HLA‐A, ‐B, ‐DR; Bf and C4 genes in 54 rheumatoid arthritis (RA) and 24 control families. There were no statistically significant differences in C4A or C4B gene frequencies between RA and control groups, although there were trends for C4B*Q0 to be reduced and C4B2 to be increased in DR4 positive RA compared with DR4 positive controls. The lack of any strong association between C4 variants and RA overall makes it unlikely that the association between RA and genes within the MHS represents a direct effect of variants within the C4A or C4B loci themselves. On comparison of DR4‐bearing haplotypes, the haplotype B15‐BfS‐DR4 was increased fourfold and the B44‐BfS‐DR4 haplotype was less frequent in the RA group. When C4 variants were also considered, the haplotype B44‐C4B*Q0‐C4A3‐BfS‐DR4 was nine times less frequent in RA patients than in controls. The observation that different DR4 bearing haplotypes may confer either increased or decreased susceptibility to RA suggests either that it is unlikely that DR4 itself is involved in the disease process or that specific haplotypic combinations are important. Thirty‐two RA patients were HLA‐DR4 negative. No single DR4 negative haplotype was found to confer significantly inc

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01673.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

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<0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p<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<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). By using a DQ‐beta probe and a range of restriction enzymes, the DNA of Dw typed DR4 positive RA patients and controls was classified into either the omega or phi restriction fragment length polymorphism (RFLP) patterns. No obvious inclination towards one of these patterns was observed with Dw4 or Dw14. However, when haplotypes were considered, the majority of the B44‐DR4‐Dw4 haplotypes were the phi pattern, whereas the Bw62‐DR4‐Dw4 and the Bw60‐DR4‐Dw14 haplotypes were omega. There was an indication that Dw10 is associated w

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01674.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01675.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The HLA antigen Aw43 has been observed only in Southern African populations. In order to confirm its identity and clarify its definition, ten cells with this specificity were shipped to laboratories in England, the United States of America and Australia to be tested with the sera from the 10th International Histocompatibility Workshop. The results of tests on nine of these cells which were sufficiently viable indicated that HLA‐Aw43 is a distinct serological specificity which could be distinguished from both the A10 cross‐reacting group (A25, A26 and Aw34) and A29. The Aw43 specificity segregated in two South African Negro families, and occurred commonly in association with Bw70. The occurrence of HLA‐Aw43 in South African Caucasoids, in contrast to its absence in other Caucasoid groups, is probably due to genetic admixture with indigenous South African popula

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01676.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

No HLA‐A, B, C, DR, DQ association was found in 80 Chinese IgA nephropathy patients. In addition, no prognostic genetic marker was discovered. The subgroup of those with gross hematuria was immunogenetically distinct from the subgroup of those without gross hematuri

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1989.tb01677.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY