The influence of HLA matching in cardiac allograft recipients in a single center.
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Cyclosporins↗
Biomedical subjects
M Busson
Publications and source records attributed to M Busson.
Can the profile of preformed HLA antibodies in highly sensitized recipients influence the outcome of their kidney transplants?
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Graft Survival↗
[HLA markers and complotypes: risk factors in systemic lupus erythematosus?].
Sixteen simplex and two multiplex families of subjects presenting with systemic lupus erythematosus (SLE) were studied and compared with 108 controls. The frequency of A1, B8 and DR3 alleles reported in the literature was not confirmed. Only the DR3 (chi 2 = 5.45, p less than 0.02, RR = 2.53) and CW4 (chi 2 = 6.72, p less than 0.01) alleles, not yet described by other authors, were noted as being associated with SLE. The DR3 C21 BFS C4 AQ0B1 B8 A1 haplotype was not found with statistically significant frequency (chi 2 = 2.55, p = NS). The distribution of haplotypes within the multiplex families confirmed the absence of link between the major histocompatibility complex and systemic lupus erythematosus. Finally, the association of a null allele of complement was confirmed (chi 2 = 5.08, p less than 0.05), but only the C4 BQ0 allele was associated with SLE (chi 2 = 12.27, p less than 0.001, RR = 3.78) instead of the C4 AQ0 allele reported in the literature as being associated with SLE. Some of the CMH alleles are thought to constitute a risk factor of SLE. The presence of silent alleles of complement (C2 Q0, C4 AQ0 and C4 BQ0) seems to play a decisive role in the occurrence and expression of this disease.
Adult↗
[4 varieties of islet cell antibodies in 74 insulin-dependent diabetics and their families as a function of the HLA genotype].
The sera of 74 diabetic patients and of their first degree relatives were studied for 4 different types of islet cell antibodies (ICA, CFICA, ICSA, ICACT) and the results were compared according to the HLA genotype. Seventy two percent of the patients' sera were positive for at least one type of auto-antibody. Two types of auto-antibodies were observed: anticytoplasmic antibodies (ICA and CFICA), and surface antibodies (ICSA and ICACT). The different types of antibodies were not associated with any HLA-DR. These antibodies were also present in 15% of the healthy relatives. The fact that they were detected in the sera of siblings sharing no haplotype with the proband, some of them bearing neither DR3 nor DR4 antigens, suggests that non HLA linked genes and/or environmental factors partly control their secretion.
Autoantibodies↗
Update on ibuprofen: review article.
Non-steroidal anti-inflammatory drugs (NSAIDs) have become the principal mode of therapy for rheumatic diseases and their use has continued to increase despite concern expressed recently regarding potential hazards (Figure 1). Prior to 1969, a limited number of NSAID drugs were available. Aspirin and indomethacin became the mainstay of treatment but tolerability, particularly gastric irritation, at doses necessary to control rheumatic symptoms limited the usefulness of these valuable agents. The pyrazolone, phenylbutazone, showed slightly better gastro-intestinal (GIT) tolerability but has since been associated with an increased risk of blood dyscrasiae and is now only available for restricted use in most countries. Ibuprofen was the first of a new breed of NSAIDs originally introduced into the United Kingdom in 1969. Chemically quite distinct from its forerunners it was the first of the propionic acid derivatives to be used in rheumatic practice. The propionics have since become the largest, single and most important group of NSAIDs accounting for 50% of NSAID prescriptions in the United Kingdom. It is estimated that over 100 million patients worldwide have received ibuprofen which is now available in over 100 countries throughout the world including all the major markets. Ibuprofen was developed directly as a result of the problems associated with the use of corticosteroids in the treatment of rheumatoid arthritis and also because of the gastro-intestinal irritation and general intolerability of the established NSAIDs, at that time. Ibuprofen was readily accepted because, unlike the previous drugs, its therapeutic efficacy was easily seen to outweigh the severity of its side-effects. Ibuprofen was the first new drug with the potency of aspirin but without its major disadvantages.
Analgesia↗
A long-term study of flurbiprofen in rheumatological disorders: I. Rheumatoid arthritis.
Eight hundred and forty-two patients undergoing treatment for rheumatoid arthritis in hospital centres in the United Kingdom were evaluated as part of a long-term, variable dose study of the efficacy and safety of flurbiprofen in 1,396 patients with a variety of rheumatological disorders. Highly significant (p less than 0.001) improvements were evident in morning stiffness, grip strength, joint size, articular index and functional capacity at the end of the 18-month observation period reported here, as was a decrease in pain severity in all sub-groups, including those patients entering the study because of lack of effect of their previous therapy. Global assessments by doctor and patient showed highly significant improvements over this time period for both young and older patients, in whom objective improvements were less striking. Sixty-four per cent of side-effects reported were gastro-intestinal, CNS side-effects (headache, giddiness) accounting for 14%. The incidence varied according to whether or not concomitant therapy was being prescribed. Side-effects in the elderly were similar in nature to those in younger patients.
Adult↗
A long-term study of flurbiprofen in rheumatological disorders: III. Other articular conditions.
A total of 336 patients with ankylosing spondylitis, psoriatic arthropathy or miscellaneous articular disorders were evaluated over 12 months as part of an open, out-patient, multicentre study in the United Kingdom of the efficacy and safety of the non-steroidal anti-inflammatory drug (NSAID) flurbiprofen (Froben) in a total of 1,396 patients with a variety of rheumatological disorders. Significant improvements in pain were found for patients in all groups from the second week onwards, for up to 6 months in those with ankylosing spondylitis, and for up to 12 months of treatment for those with psoriatic arthropathy or other articular conditions. Global assessments of progress in patients taking flurbiprofen in the therapeutic range of 150-400 mg daily for a minimum of 6 months were recorded by doctor and patient. Improvement of patients in all groups reached statistical significance after 1 month's treatment and remained significant at 12 months. The incidence of side-effect reporting over-all was 17.2%, being higher in men than in women in the group receiving no concomitant therapy and doubling in patients receiving NSAIDs in addition to flurbiprofen. Side-effects were similar in nature to those of other drugs in this group.
Adolescent↗
A long-term study of flurbiprofen in rheumatological disorders: II. Osteoarthrosis.
Two hundred and twenty-one patients with osteoarthrosis were evaluated over 18 months in the course of an open, multicentre study in the United Kingdom of the efficacy and safety of the non-steroidal anti-inflammatory drug (NSAID) flurbiprofen (Froben), in which a total of 1,396 patients with a variety of rheumatological disorders took part. Highly significant (p less than 0.001) improvements in pain sources were reported during the first 6 months of treatment, remaining significant for the rest of the 18 months of the study, and a global evaluation of progress made by doctor and patient recorded highly significant improvements by both. Improvement was particularly marked in those who had failed to respond to a previously administered drug, and in the elderly. Side-effects occurred in 21% of those not receiving other NSAIDs concomitantly, and were higher in women than in men who took other drugs at the same time. Side-effects were similar in nature to those of other drugs in this group and no correlation in their frequency or severity with the dosage of flurbiprofen was found.
Adult↗
[Usual statistical methods for studying HLA-disease associations and linkages].
Statistical methods used for the study of correlation and/or linkage between HLA and diseases susceptibility will be different according to the aim of the study. In case of a search of an association between disease character and HLA markers in unrelated populations, the methodology used will be based upon chi square and Relative Risk. In case of linkage study: multiplex families with 2 or more patients bring the most informative data. In all cases, a particular attention must be paid to criteria used for selection of patients and controls, and for studies of linkage to the hypothesis concerning mode of inheritance and penetrance required by the model chosen.
Alleles↗
[Familial studies of systemic lupus erythematosus. HLA markers and complotypes].
Particular susceptibility to systemic lupus erythematosis (SLE) could be due to a certain alleles of class I, II or III of the major histocompatibility complex (MHC). The existence of total hereditary deficiencies of factor 2 or 4 of the complement in this syndrome suggests the presence of silent alleles which could conceivably play a determining role in the appearance of SLE. In this study, the HLA haplotypes and complotypes (C2, C4, Bf) were determined in 20 individuals suffering from SLE, and compared with 108 healthy, genotyped individuals. The results obtained showed a significant increase in the frequency of C4 BQ0 in patients compared with that found in controls (chi 2 = 12.27, p less than 0.001, Relative Risk = 3.78), and confirm the HLA association, DR3/SLE (chi 2 = 5.45, p less than 0.02, RR = 2.53).
Adult↗
[Organ transplantation in France in 1984 (activity report of France-Transplant)].
Nine hundred and seventy four renal transplantations were performed in 1984, thus attaining a total 7927 grafts made in France at the end of 1984. The numbers of heart transplantations (77), to which 100 prospects in 1985 can be added, as well as liver grafts (13) plus 50 prospects in 1985, are showing a spectacular increase. Although the considerable improvement of heart graft and liver graft results can be attributed, essentially to the use of Cyclosporine, this trend can be dependent in the case of kidney transplantations also on transfusions before and on a better HLA-B DR compatibility which can in optimal situations represent a respective gain of 10% and 15% of graft survival.
Adult↗
Effects of HLA genotype, age and birth order on empirical risk estimates for insulin-dependent diabetes in siblings of diabetic children. An actuarial evaluation.
The incidence of insulin-dependent diabetes (IDDM) was evaluated as a function of time of follow-up among the 371 siblings of 193 diabetic children using actuarial methods and comparisons were carried out according to HLA genotype, sex, age and birth order. The following parameters appeared to be relevant for empirical discrimination in terms of the risk of recurrence of the disease among siblings: The number of HLA-haplotypes shared with the first affected sibling considered as the proband. Cumulative proportions 15 yr after onset of IDD in the proband were 35%, 20% and 3% in the case of 2, 1 and 0 haplotypes in common, respectively (p less than 0.02). The birth order. Cumulative risk estimates were 26% for sibs born after the proband and 11% for sibs born before the proband (p less than 0.001). The age. Risk estimates were 24% for sibs who were aged less than 10 yr at the time of the proband's onset and 5% in sibs aged greater than 10 yr (p less than 0.001). The joint analysis of birth order or age with HLA genotypes showed significantly higher risks for both identical and haplo-identical sibs with later birth order and/or younger age. Even though these results do not reflect true incidence rates because of retrospective recruitment of part of the material, the comparison of the risk figures points out the important role of some age-related effect, probably environmental, in addition to the genetic susceptibility borne by MHC genes.
Birth Order↗
[Hope of HLA-compatible renal transplantation for hyperimmunized patients].
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HLA Antigens↗
A systematic study of HLA class II-beta DNA restriction fragments in insulin-dependent diabetes mellitus.
DNA restriction fragments of the genes encoding HLA class II-beta antigens were compared in 34 patients with insulin-dependent diabetes mellitus and 34 HLA-DR-matched healthy individuals. Ninety-three fragments, determined by six restriction enzymes (EcoRI, EcoRV, HindIII, BamHI, Pvu II, and Taq I), were analyzed: (i) A DR Taq I 12.7-kilobase-pair fragment might be a marker for the extended haplotype HLA-B8, DR3. (ii) In controls, DR4 haplotypes are associated with two distinct clusters of DQ restriction fragments (DQR4 and DQR5). Almost all (94%) DR4 patients belong to the DQR4 and not to the DQR5 cluster. This suggests that, among HLA-DR4 haplotypes, only DQR4 haplotypes are involved in susceptibility to insulin-dependent diabetes mellitus. (iii) A DR Taq I 14.5-kilobase-pair fragment was found to be strongly associated with DQR4, mainly in DR3/DR4 heterozygous patients (P = 5 X 10(-4). However, these results must be interpreted with caution, taking into account the high number of statistical tests performed.
DNA Restriction Enzymes↗
HLA antigens and toxic reactions to sodium aurothiopropanol sulphonate and D-penicillamine in patients with rheumatoid arthritis.
One hundred and forty-one patients with rheumatoid arthritis treated with aurothiopropanol sulphonate or D-penicillamine, or both were examined for HLA antigens to investigate the genetic influence on the occurrence of different adverse reactions during therapy. All 13 patients possessing HLA-DR3 had toxic reactions. The relative risk for DR3 positives of developing skin eruptions or proteinuria was calculated to be 10.5 times and seven times respectively that of DR3 negatives. The incidence of DR7 antigen in 94 patients with toxic reactions was significantly decreased (11% compared with 28% in controls) suggesting a protective role for this antigen.
Adult↗
[Results of 310 cadaver kidney transplants in children and adolescents].
This study reports the results of 310 cadaver kidney transplantations in 295 children and adolescents performed from 1973 to 1983. The actuarial survival of patients was 97% at one year and 92% at 5 years; that of grafts was 79% at 1 year and 65% at 5 years, these rates having improved during the last years. Results were similar and even better for the 18 second transplantations. Among the causes of failure, rejection comes first (65%), then thromboses of renal artery (13%) and relapses of oxalosis or steroid resistant nephrosis (12%). Patients with cytotoxic antibodies have a less good survival of grafts, especially after 5 years. HLA A and B compatibility is a factor of success. Among complications hypertension is frequent, 53% of patients receiving antihypertensive treatment after 1 year. It is sometimes severe and was responsible for death in 5 cases. Growth was variable after transplantation: 25% of children before puberty had a catch-up curve, 25% had an unchanged growth and 50% an increased retardation. The average standard deviation was near zero but it was -0.49 SD/year in patients with creatinine level greater than or equal to 150 mumol and +0.24 SD in children under alternate day steroid therapy. Rehabilitation was excellent, less than 3% of patients not being engaged in any activity 1 year after transplantation.
Adolescent↗
Segregation of HLA-DR2 among affected and non-affected offspring of 66 families with type 1 (insulin-dependent) diabetes.
Segregation of HLA-DR2 among affected and unaffected offspring was studied in 66 HLA-genotypes families with Type 1 diabetes in whom at least one parent carried DR2. The frequency of DR2-positive parents (21%) was not different from that of control families (29%). Among the diabetic probands, the gene frequency of DR2 was significantly decreased compared with control subjects (0.05 versus 0.17, p less than 0.001) as were DR5 (0.07 versus 0.17, p less than 0.01) and DR7 (0.06 versus 0.13, p less than 0.003). Twenty probands carried DR2, in 11 or whom (55%) it was found in combination with either DR3 or DR4. The nine cases who carried another DR allele included one who was DR2 homozygous. Transmission of DR2 was reduced in affected offspring, and random in unaffected siblings, compared with the expected ratio. However, when the DR2 transmission was analysed separately for parents bearing DR2 with DR3, DR4 or another DR allele, it appeared that DR2 transmission to affected offspring was random when the parents carried neither DR3 or DR4, the transmission deficit being due to over-transmission of DR3 and DR4. The haplotype analysis showed that the haplotype A3, Cw7, B7, GfS, DR2, found in 19% of "non-diabetic" DR2 haplotypes was practically absent among "diabetic" DR2-haplotypes (4%). In conclusion, population and segregation analysis could not demonstrate a specific protective effect of DR2.
Diabetes Mellitus, Type 1↗
Influence of HLA-A, B, and DR matching on the outcome of kidney transplant survival in preimmunized patients.
The outcome of 893 prospectively typed (HLA-A, B, and DR) and matched cadaveric kidney transplants--all first grafts, with patients being transfused before transplantation--was studied using actuarial survival methods. The effect of HLA-A, B and DR matching was only found to be significantly beneficial to graft survival in the group of 289 presensitized recipients: 70% and 43% graft survival at two years in the case of best-matched (4-6 HLA-A, B, and DR) identities versus mismatched (0 and 1 HLA-A, B, and DR) identities, respectively (P = 0.05). Although a cumulative effect of matching for antigens belonging to the 3 HLA-A, B, and DR series was observed among the group of preimmunized recipients, a trend arose in favor of the prominent role of the HLA-B alleles. No significant difference related to HLA matching was observed in the group of nonsensitized recipients. These results confirm previous observations and support efforts to give priority for matched kidneys to preimmunized patients.
Actuarial Analysis↗