RÉSUMÉ
BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma is a high accurate test for prenatal screening for Down syndrome. Although it has been reported to be cost effective as a contingent test, evidence about its budget impact is lacking. OBJECTIVE: To evaluate, using computer simulations, the budget impact of implementing NIPT as a contingent test in the Quebec Program of screening for Trisomy 21. METHODS: A semi-Markov analytic model built to simulate the budget impact of implementing NIPT into the current Quebec Trisomy 21 public Prenatal Screening, Serum Integrated prenatal screening (SIPS). Comparisons were made for a virtual population similar to that of expected Quebec pregnant women in 2015 in terms of size and age. Data input parameters were retrieved from a thorough literature search and in government databases, especially data from Quebec Program of screening for Trisomy 21. The 2015-2016 fiscal year budget impact was estimated from the Quebec healthcare system perspective and was expressed as the difference in the overall costs between the two alternatives (SIPS minus SPS + NIPT). RESULTS: Our study found that, at a baseline cost for NIPT of CAD$ 795, NIPT as a second-tier test offered to high-risk women identified by current screening program (SIPS + NIPT) may be affordable for Quebec health care system. Compared to the current screening program, it would be implemented at a neutral cost, considering a modest annual savings of $ 80,432 (95% CI $ 79, $ 874-$ 81,462). Results were sensitive to the NIPT costs and the uptake-rate of invasive diagnostic tests. CONCLUSION: Introducing NIPT as a contingent test in the Quebec Trisomy 21 screening program is an affordable strategy compared to the current practice. Further research is needed to confirm if our results can be reproduced in other healthcare jurisdictions.
RÉSUMÉ
Although noninvasive prenatal testing (NIPT) for aneuploidies using cell-free fetal DNA in maternal blood has been reported to have a high accuracy, only little evidence about its cost-effectiveness is available. We systematically reviewed and assessed quality of economic evaluation studies published between January 1, 2009 and January 1, 2016 where NIPT was compared to the current screening practices consisting of biochemical markers with or without nuchal translucency (NT) and/or maternal age. We included 16 studies and we found that, at current level of NIPT prices, contingent NIPT provide the best value for money, especially for publicly funded screening programs. NIPT as first-line test was found not cost-effective in the majority of studies. The NIPT unit cost, the risk cut-offs for current screening practice, the screening uptake rates (first- and second-line screening) as well as the costs and uptake rates of invasive diagnostic screening were the most common uncertain variables. The overall quality of included studies was fair. Considering a possible drop in prices and an ongoing NIPT expansion to include other chromosomes abnormalities other than T21, T18, T13 and sex chromosomes aneuploidies, future research are needed to examine the potential cost-effectiveness of implementing NIPT as first-line test.
Sujet(s)
Aneuploïdie , Acides nucléiques acellulaires , Maladies chromosomiques/diagnostic , Maladies chromosomiques/génétique , Diagnostic prénatal , Analyse coût-bénéfice , Femelle , Coûts des soins de santé , Humains , Grossesse , Diagnostic prénatal/économie , Diagnostic prénatal/méthodesRÉSUMÉ
BACKGROUND: Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. OBJECTIVE: To compare the cost effectiveness of various CF NBS options. METHODS: A Markov model was built to simulate the cost effectiveness of various CF-NBS options for a hypothetical CF-NBS program over a 5-year time horizon assuming its integration into an existing universal NBS program. NBS simulated options were based on a combination of tests between the two commonly used immunoreactive trypsinogen (IRT) cutoffs (96th percentile and 99.5th percentile) as first tier tests, and, as a second tier test, either a second IRT, pancreatic-associated protein (PAP) or CFTR mutation panels. CFTR mutation panels were also considered as an eventual third tier test. Data input parameters used were retrieved from a thorough literature search. Outcomes considered were the direct costs borne by the Quebec public health care system and the number of cases of CF detected through each strategy, including the absence of screening option. RESULTS: IRT-PAP with an IRT cutoff at the 96th percentile is the most favorable option with a ratio of CAD$28,432 per CF case detected. The next most favorable alternative is the IRT1-IRT2 option with an IRT1 cutoff at the 96th percentile. The no-screening option is dominated by all NBS screening protocols considered. Results were robust in sensitivity analyses. CONCLUSION: This study suggests that NBS for cystic fibrosis is a cost-effective strategy compared to the absence of NBS. The IRT-PAP newborn screening algorithm with an IRT cutoff at the 96th percentile is the most cost effective NBS approach for Quebec.
Sujet(s)
Simulation numérique , Protéine CFTR/génétique , Mucoviscidose/diagnostic , Mucoviscidose/économie , Dépistage néonatal/économie , Dépistage néonatal/méthodes , Algorithmes , Antigènes néoplasiques/métabolisme , Marqueurs biologiques/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Enfant d'âge préscolaire , Analyse coût-bénéfice , Mucoviscidose/métabolisme , Dépistage génétique/économie , Dépistage génétique/méthodes , Humains , Nourrisson , Nouveau-né , Lectines de type C/métabolisme , Chaines de Markov , Protéines associées à la pancréatite , Sensibilité et spécificité , Trypsinogène/métabolismeRÉSUMÉ
Screening for hereditary hemochromatosis, although largely discussed, is not yet implemented in clinical practice. We evaluated the cost-effectiveness of 165 hemochromatosis population-screening algorithms involving two or three of several screening tests by developing a computer program that simulates all possible screening scenarios. Input data comprised government estimates of health services data and costs and a virtual population with user-defined demographic characteristics (including variable HFE mutation frequencies and penetrance values). We show that when C282Y homozygote prevalence is set at 3:1000, population screening appears cost-effective when penetrance of the biochemical phenotype is >0.70. When only hepatocellular carcinoma and cirrhosis are considered as the cost-driving complications, population-based screening is not significantly more cost-efficient than no screening, but life expectancy of individuals identified with hereditary hemochromatosis and treated is still improved by 7 years. Among the 165 screening algorithms tested in 91 different virtual populations of one million individuals, biochemical tests usually perform better as the initial test than genetic testing. Indeed, the genetic testing is most cost-effective as the final confirmatory test. Finally, for most combinations of prevalence and penetrance of HFE, one screening algorithm--unbound iron-binding capacity + transferrin saturation--appeared robust enough to be always within the top 5 most cost-effective strategies.
Sujet(s)
Algorithmes , Prédisposition génétique à une maladie/génétique , Dépistage génétique/économie , Hémochromatose/épidémiologie , Hémochromatose/génétique , Mutation/génétique , Simulation numérique , Analyse coût-bénéfice , Dépistage génétique/méthodes , Humains , PrévalenceRÉSUMÉ
INTRODUCTION: The Verona Service Satisfaction Scale-French version (13) was translated and adapted from the Italian version of Verona Service Satisfaction Scale (27). The VSSS makes it possible to evaluate the satisfaction of people with serious mental illness with respect to the services. The original VSSS-54 contained 7 dimensions: 1) Overall satisfaction, 2) Professionals' skills and behaviour, 3) Information, 4) Access to services, 5) Services efficacy, 6) Relatives' involvement and 7) Types of interventions. According to factorial analyses carried out by Ruggeri et al., the dimensions Information and Access to services were aggregated. However, no factorial analysis was carried out in order to verify the six dimension-structure of the VSSS. From an international perspective, the study entitled "The European Psychiatric Services: Inputs linked to Outcome Domains and Needs (EPSILON)" achieved the standardisation of different questionnaires in several languages (2). A new version of the VSSS entitled "Verona Service Satisfaction Scale-European version" (VSSS-EU) was developed and is now available in the following languages: Italian, Danish, German, English and Spanish. In order to compare in different countries the satisfaction of people with serious mental illness with respect to services, we undertook from 1998 to ascertain the psychometrical properties of the French version of the VSSS. (13). Confirmatory Factorial Analysis (CFA) was carried out on the six dimension-structure of the VSSS-54F: 1) Overall satisfaction, 2) Professionals' skills and behaviour, 3) Information and Access to services, 4) Services efficacy, 5) Relatives involvement and 6) Types of interventions. For each dimension, consistency analysis (Cronbach's alpha) was computed in order to bring forth additional psychometrical properties of the VSSS-54F. PARTICIPANTS: 150 clients involved in an intensive case management program and supported by 30 mental health workers, filled out the VSSS-54F questionnaire. These clients were comprised of 110 women and 40 men, their ages ranging from 22 to 90 years (M = 51.7, SD = 14.7). Among them, 65 (43.3%) had a diagnosis of schizophrenia or another form of psychosis, 56 (37.3%) had an affective disorder, 17 (11.3%) had anxious disorders and 7 (7.7%) other. DATA ANALYSES: Using the EQS Software (3), Confirmatory Factor Analyses (CFA) were carried out in this study. Thus, 'the evaluation of the models' fit with the empirical data was carried out by taking into account various statistical indices. In addition to the Chi square/df ratio, the indices of adjustment such as the "NonNormed Fit Index" (NNFI), the Comparative Fit Index (CFI), robust CFI (calculated starting from the Satorra-Bentler Chi Square) as well as the RMSEA (Root Mean Standard Error of Approximation) were used to measure the fit of the models. Moreover, the estimation method "Maximum Likelihood-Robust" was carried out in order to evaluate the models. RESULTS: The original model with 6 dimensions (M1) does not present satisfactory fit indices. Indeed, the Chi Square/df ratio is above 2, the NNFI, CFI and CFI robust indices are lower than. 90 and the RMSEA is higher than. 08. Most items from Types of intervention dimension presented saturation lower than.30, and consequently indicate that these items are not correlated significantly with their dimension. We notice also some correlations between error terms of the three items of Overall Satisfaction scale and other items of the VSSS questionnaire. Considering these last results and the direction taken in VSSS-EU by breaking down by profession items of Professionals' skills and behaviour scale, we obtained a new model (M2). The five dimensions of this model are as follow: 1) Psychiatrists/Psychologists' skills and behaviour (7 items), 2) Nursing staff/social workers' skills and behaviour (7 items), 3) Information and access to services (3 items), 4) Services efficacy (5 items), 5) Relatives' involvement (3 items). When we test this model, the fit indices are satisfactory: the Chi Square/df is 1.36, the NNFI, CFI and robust CFI indices are near or higher than 0.90, respectively 0.88, 0.89 and 0.94. Finally, the RMSEA index is 0.08. In addition, the correlations between five dimensions are significant and vary from 0.58 to 0.87 (p < 0.05). The internal consistency coefficients for each new scale are all satisfactory, and vary from .83 to .91, except for the Information and access to services scales. But this latter finding shall be evaluated knowing that acceptable alpha can be close to .60 when scales count less than four items (16). CONCLUSION: This study confirms with some adjustments the factorial structure of the VSSS. The results indicate five dimensions (25 items): Psychiatrists/Psychologists' skills and behaviour, Nursing staff/social workers' skills and behaviour, Information and access to services, Services efficacy, Relatives' involvement. Even if the Type of interventions dimension was not retained in the model, we suggest preserving it for eventual clinical evaluation based on each item. We also suggest, for future studies, the adaptation of the VSSS-54F to the European version, VSSS-EU. Indeed, the results of our study sustain the European version because the VSSS-EU is more focused since it separates the skills and behaviour of psychiatrists, psychologists, nurses and social workers (e.g. items 3a and 3b or items 22a and 22b). The next step in the validation process would be to measure Inter-rater and test-retest reliability as well as concurrent, convergent and discriminant validity of the VSSS-EU. Furthermore, a multicultural comparison of the VSSS-EU would be required if the instrument is used for interesting comparisons of survey.
Sujet(s)
Langage , Services de santé mentale/normes , Satisfaction des patients , Enquêtes et questionnaires , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Canada , Femelle , Humains , Mâle , Adulte d'âge moyen , Reproductibilité des résultatsRÉSUMÉ
BACKGROUND: Although pharmacoeconomic studies constitute a valuable tool for better managing drug consumption, the conditions under which such studies would be performed in Latin American countries have not been explored. OBJECTIVES: The aim of this paper is to evaluate the potential advantages of and pitfalls in doing pharmacoeconomic research in Latin America and to propose avenues to facilitate the development of this field in the region. METHODS: The Canadian guidelines for the economic evaluation of pharmaceuticals served as a structured framework to assess, both prospectively and retrospectively, the conditions under which the pharmacoeconomic component of a clinical trial held in Mexico and Brazil would be and actually was conducted. RESULTS: The conditions under which pharmacoeconomic evaluations are conducted must be improved if studies are to contribute to the better management of scarce resources across the entire health care system. CONCLUSIONS: The creation of a public funding agency, the reappraisal of administrative data as a management tool in both the public and the private sectors, and the establishment of national guidelines should be considered within the framework of reforms aimed at allowing healthcare systems to meet their objectives of efficiency and equity.
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Essais cliniques comme sujet/économie , Évaluation de médicament/économie , Pharmacoéconomie , Brésil , Analyse coût-bénéfice , Coûts des médicaments , Recommandations comme sujet , Humains , Amérique latine , Mexique , Études multicentriques comme sujetRÉSUMÉ
BACKGROUND: With the psychiatric deinstitutionalization movement in its fourth decade, questions are being raised concerning its relevance for long-stay inpatients with severe disabilities and the risk that those discharged into the community may be abandoned. METHODS: A random sample taken in 1989 of long-stay inpatients at Louis-H Lafontaine Hospital made it possible to examine 96 pairs of patients. Each pair included 1 patient discharged between 1989 and 1998 and 1 patient hospitalized. Pairs were matched for sex, age, length of stay, and level of psychiatric care in 1989. Patients and staff were interviewed using standardized questionnaires, and case notes were reviewed to assess symptoms, daily living skills, residential status, quality of residential setting, and clinical and social problems and needs. RESULTS: The investigation revealed that discharged patients moved to highly supervised settings, which included professionally supervised group homes, supervised hostels, and foster families. About 20% went to nursing homes owing to loss of autonomy from physical disorders. Only 4 discharged patients were lost to follow-up, of whom 2 were probable vagrants. Both those discharged and those remaining as inpatients presented with major clinical problems and daily living skill deficits. The care needs of discharged patients were generally met, and placement in the community was considered appropriate. Of those who had remained hospitalized, over one-half could be moved to supervised settings immediately, or after 1 to 2 years' preparation in a discharge unit, while 13% could be moved to nursing homes. Over 25% required intensive, individualized rehabilitation treatment targeting engagement, psychotic symptoms, withdrawal, and dangerous and socially embarrassing behaviours. CONCLUSION: Deinstitutionalization in the largest Canadian psychiatric hospital did not lead to patient abandonment in the community.
Sujet(s)
Désinstitutionnalisation , Taille d'établissement de santé , Besoins et demandes de services de santé , Hôpitaux psychiatriques , Soins de longue durée , Troubles psychotiques/rééducation et réadaptation , Activités de la vie quotidienne/psychologie , Adolescent , Adulte , Sujet âgé , Services communautaires en santé mentale , Femelle , Humains , Mâle , Adulte d'âge moyen , Sortie du patient , Échelles d'évaluation en psychiatrie , Troubles psychotiques/diagnostic , Troubles psychotiques/psychologie , QuébecRÉSUMÉ
BACKGROUND: The cost-effectiveness of the eventual deinstitutionalization of patients with severe and persistent mental disorders who are currently hospitalized in long-term care remains a controversial matter. METHODS: A retrospective cohort of 96 pairs of psychiatric hospital patients with 1 member deinstitutionalized between 1989 and 1998 was followed up for nearly 10 years. All use of medical and social services was documented. Patients were evaluated at the start and end of the study on various clinical and social dimensions, as well as on quality of life. RESULTS: On several dimensions, deinstitutionalized patients scored more positively than did those patients still hospitalized. The lower daily cost of living accommodations for deinstitutionalized patients easily offsets the cost of services required for treatment in the community. CONCLUSION: Deinstitutionalization, as implemented in the hospital studied, remains for many patients a less costly option than continued hospitalization and is likely to improve their mental state and well-being.
Sujet(s)
Désinstitutionnalisation/économie , Soins de longue durée/économie , Troubles psychotiques/économie , Adulte , Sujet âgé , Études de cohortes , Services communautaires en santé mentale/économie , Analyse coût-bénéfice , Femelle , Hôpitaux psychiatriques/économie , Humains , Mâle , Adulte d'âge moyen , Troubles psychotiques/rééducation et réadaptation , Québec , Études rétrospectivesRÉSUMÉ
BACKGROUND: Few studies have been conducted of the organizational aspects that impact on the course of psychiatric deinstitutionalization. METHOD: A case study was undertaken of 10 years of deinstitutionalization in a Montreal psychiatric hospital. RESULTS: Deinstitutionalization has forged ahead in the hospital over the past few years, although the course it has taken is not the one initially plotted by its promoters. Care management of deinstitutionalized patients remains under the control of the psychiatric hospital and its physicians. However, the patients' well-being has remained a focus of concern and does not seem to have been detrimentally affected by this development. CONCLUSION: Deinstitutionalization is both a solution to the criticisms levelled at the hospital-psychiatric approach of managing persons with severe and persistent mental disorders and an extremely useful tool in the power struggle among the various stakeholders in mental health services reform. Deinstitutionalization has become unavoidable.
Sujet(s)
Désinstitutionnalisation/organisation et administration , Troubles psychotiques/rééducation et réadaptation , Prise en charge personnalisée du patient/organisation et administration , Maladie chronique , Hôpitaux psychiatriques , Humains , Évaluation des résultats et des processus en soins de santé , Assurance de la qualité des soins de santé/économie , QuébecRÉSUMÉ
Meconium staining of the amniotic fluid in labor is a frequent problem that is associated with an increase in the risk of neonatal and maternal morbidity. Amnioinfusion is a simple technique that is designed to prevent neonatal and maternal morbidity associated with meconium. Preliminary studies indicate that amnioinfusion is a promising approach to the prevention of such complications of labor. However, further research is required. The primary objective of this multi-centre randomized controlled study is to determine if amnioinfusion for thick meconium stained amniotic fluid results in a reduction in perinatal death or moderate to severe meconium aspiration syndrome. We will also assess the effects of amnioinfusion on other indicators of neonatal morbidity and on cesarean section. The study includes an evaluation of womens views on their childbirth experience and an economic evaluation of a policy of amnioinfusion The study will be achieved with the collaboration of approximately 50 obstetrical centres from across Canada, US, Europe, South America and South Africa. This multicentre trial will provide urgently needed information on the efficacy and effectiveness of amniofusion for the indication of meconium stained amniotic fluid.
Sujet(s)
Liquide amniotique/physiologie , Maladies néonatales/prévention et contrôle , Méconium , Études multicentriques comme sujet , Essais contrôlés randomisés comme sujet , Humains , Nouveau-né , Syndrome d'aspiration méconiale/prévention et contrôle , Sélection de patientsRÉSUMÉ
This study compared the cost-effectiveness of midwife services provided in birth centres operating as pilot projects with current hospital-based medical services in the province of Quebec. One thousand midwives' clients were matched with 1,000 physicians' clients on the basis of socio-demographic characteristics and obstetrical risk. Direct costs for the prenatal, intrapartum and postpartum periods were estimated. Effectiveness was assessed on the basis of three clinical indicators and four indices related to the individualization of care as assessed by women. Results show that the costs of midwife services were barely lower than or equal to those of physician services, but cost-effectiveness ratios were to the advantage of the midwife group, except for one clinical indicator (neonatal ventilation). Overall, this study provides rational support for the process of legalizing midwifery in the province.
Sujet(s)
Centres de naissance/économie , Coûts directs des services/statistiques et données numériques , Coûts hospitaliers/statistiques et données numériques , Infirmières sages-femmes/économie , Obstétrique/économie , Centres de naissance/normes , Analyse coût-bénéfice , Femelle , Humains , Infirmières sages-femmes/normes , Recherche en évaluation des soins infirmiers , Obstétrique/normes , Projets pilotes , Grossesse , Issue de la grossesse , Indicateurs qualité santé , QuébecRÉSUMÉ
This project established by an outreach team from the CLSC des Faubourgs in autumn 1998, studies how the members of this team perceive the impact of their clinical intervention with homeless people suffering of severe mental illness. A convenience sample (n=52) was selected within the team's clientele. The clientele's needs were evaluated with the Camberwell Assessment of Needs (CAN-F, Phelan et al., 1995). Quality of life was measured twice with the Wisconsin Quality of Life Questionnaire (Becker et al., 1993). The project shows that clinical intervention is associated with an improvement in quality of life of severely mentally ill homeless people and this despite the existence of numerous other needs that are not met. The study suggests the work done by the outreach team touches the clinical aspects and is associated with the improvement of social problems of severely mentally ill homeless people.
RÉSUMÉ
Epilepsy is a common disorder, the prevalence of which is estimated at between 0.1 and 1% of the population. Although there are a number of medications available for treating the disorder, 20 to 35% of affected individuals are resistant to standard treatments. Many of these patients could benefit from a new anti-epileptic, vigabatrin. Because the current indication for vigabatrin is as an adjunct in a specific subgroup of epileptic patients, which implies an increased cost of drug therapy, an ex ante economic appraisal of the expected consequences of its introduction in the treatment of epilepsy is valuable. This would provide decision makers with information to complement standard clinical data. Using administrative records of healthcare services utilisation by epileptic patients, we performed a simulation of the expected economic repercussions of vigabatrin use on direct costs related to disease management. The results show that whether or not the introduction of vigabatrin results in an increase or a reduction in costs to the healthcare system depends largely on 3 factors: (i) the administered dosage of vigabatrin; (ii) the effect that vigabatrin has on hospital admissions; and (iii) the proportion of epileptic patients who take the drug. Moreover, this study underlines the usefulness of administrative data in forecasting the economic impact of new health technologies.
Sujet(s)
Anticonvulsivants/économie , Épilepsie/traitement médicamenteux , Épilepsie/économie , Acide gamma-amino-butyrique/analogues et dérivés , Anticonvulsivants/usage thérapeutique , Coûts des soins de santé , Humains , Modèles économiques , Québec , Vigabatrine , Acide gamma-amino-butyrique/économie , Acide gamma-amino-butyrique/usage thérapeutiqueRÉSUMÉ
Polychemotherapy is the therapeutic option recommended for nonresectable, non-small cell lung cancer (NSCLC). However, the modest gains in survival, and the frequent and often serious adverse effects, associated with chemotherapy should also be considered when deciding on therapy. We therefore performed a cost-utility analysis of chemotherapy and best supportive care in NSCLC. Effectiveness and costs were analysed on 70 patients who were randomised to receive one of 3 treatments: VP (vindesine and cisplatin), CAP (cyclophosphamide, doxorubicin and cisplatin), or best supportive care. Subsequently, an assessment of the value of polychemotherapy and best supportive care was performed by oncology personnel using the time trade-off technique. Polychemotherapy was found to be more effective than best supportive care, but was also more costly and had a lower value score. Because of its cost utility and its higher value, best supportive care should not be discarded as an alternative for the treatment of NSCLC.
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Protocoles de polychimiothérapie antinéoplasique/économie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/économie , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/économie , Antibiotiques antinéoplasiques/économie , Antibiotiques antinéoplasiques/usage thérapeutique , Antinéoplasiques/économie , Antinéoplasiques/usage thérapeutique , Antinéoplasiques d'origine végétale/économie , Antinéoplasiques d'origine végétale/usage thérapeutique , Canada , Cisplatine/économie , Cisplatine/usage thérapeutique , Analyse coût-bénéfice , Coûts et analyse des coûts , Cyclophosphamide/économie , Cyclophosphamide/usage thérapeutique , Doxorubicine/économie , Doxorubicine/usage thérapeutique , Humains , Études rétrospectives , Analyse de survie , Vindésine/économie , Vindésine/usage thérapeutiqueRÉSUMÉ
Polymorphic MHC class II molecules determine immune responsiveness towards pathogens and also contribute to susceptibility or resistance to a number of different autoimmune diseases, including systemic lupus erythematosus (SLE). The HLA-DR and -DQ alleles of 52 patients with SLE were analyzed by serology and, for 42 patients, HLA-DRB1, -B3 and DQB1 allelic polymorphism was determined by oligotyping on PCR-amplified DNA. While we confirm the increase of DR3 (44.2% versus 16% in controls; p less than 0.001) reported by others, we observed a complete absence of DRw15(2)/DR3 and DRw15(2)/DR7 heterozygotes among Caucasian patients. Moreover HLA-DQB1 oligotyping revealed the absence of DQB1*0602/0201 heterozygotes in our panel of Caucasoid SLE patients. Since both DR3 and DR7 haplotypes share the same DQB1*0201-encoded DQ beta chain, and since DRw15 is known to be in linkage disequilibrium with DQA1*0102, it can be predicted that DQA1*0102/DQB1*0201 combinations are absent in Caucasian patients. We therefore propose that a DQA1*0201/DQB1*0201-encoded HLA-DQ trans-dimer formed in these heterozygotes might function as a suppressor-inducer molecule that confers resistance against SLE.
Sujet(s)
Antigènes HLA-DR/génétique , Hétérozygote , Lupus érythémateux disséminé/génétique , /génétique , Technique de Southern , Amplification de gène , Antigènes HLA-DQ/génétique , Antigènes HLA-DQ/immunologie , Sous-types sérologiques HLA-DR , Humains , Lupus érythémateux disséminé/immunologie , Réaction de polymérisation en chaîne , Polymorphisme génétique/génétiqueRÉSUMÉ
The specificity recognized on normal allogeneic cells by a given alloreactive (1-anti-A) natural killer clone is controlled by a gene locus termed EC1. Because the EC1 locus was previously shown to be located on chromosome 6, families characterized by a recombinant major histocompatibility complex haplotype were analyzed to map this locus more precisely. The breakpoint of recombination was studied by standard HLA typing, complement typing, and restriction fragment length polymorphism analysis of a series of genes located between the complement cluster genes and HLA-B within the major histocompatibility complex region. Three of 10 families analyzed were informative. From the data obtained, the EC1 locus maps between BF and HLA-B and presumably is one of the normal genes recently described in this region.