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M Abbal

Publications and source records attributed to M Abbal.

At least 19 recordsLinked to original sources

Microsatellite typing of the human leucocyte antigen region: analytical approach and contribution to rheumatoid arthritis immunogenetic studies.

Within the major histocompatibility complex (MHC), the human leucocyte antigen (HLA)-DRB1 locus is clearly associated with rheumatoid arthritis (RA). Using a microsatellite (MSat) typing approach, we aimed to identify other loci associated with RA susceptibility and/or severity within the MHC. A panel of nine MSat HLA loci [D6S291, D6S2876 (G51152), D6S1666 (DQCAR II), D6S273, D6S2789 (TNFd), D6S2810 (MIB), D6S265, D6S2222, D6S2239], and HLA-A, -B and -DRB1 genes were typed in 170 RA cases and 282 controls. For susceptibility analysis, MSat and HLA allele distribution were compared between cases and controls, before and after stratification on HLA-DRB1*04. Haplotype frequencies were estimated using an expectation-maximization algorithm in a permutation test procedure. For severity analysis, we compared the distribution of structural damage score at onset and after 4 years of follow-up in RA cases carrying susceptibility alleles. Two MSat polymorphisms were positively associated with RA susceptibility: allele*136 of D6S265 [odds ratio, OR (confidence interval, CI) = 1.55 (1.11-2.17), P= 0.007], allele*116 of D6S2239 [OR = 1.34 (1-1.79), P= 0.03] and HLA-A2 [OR = 1.46 (1.08-1.98), P= 0.01]. Two MSat polymorphisms were negatively associated with RA susceptibility: allele*133 of D6S273 [OR = 0.3 (0.1-0.75), P= 0.005] and allele*177 of D6S291 [OR = 0.72 (0.53-0.96), P= 0.02]. The association between allele*136 of D6S265 and RA susceptibility remained unchanged after stratification on HLA-DRB1*04. The haplotypic analysis showed an overrepresentation of D6S265*136/HLA-A*02 haplotype, which suggests an effect independent of HLA-DRB1 locus in RA susceptibility. While HLA-A2 and HLA-DR4 were associated with RA severity, no MSat polymorphism was associated with structural damage score.

Arthritis, Rheumatoid↗

Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort.

OBJECTIVE: To determine whether systemic markers of bone, cartilage, and synovium can predict structural progression of osteoarthritis (OA). METHODS: Patients with painful hip OA were treated with diacerein or placebo in a multicentre, prospective, double blind, 3 year follow up trial. The following information was collected at entry: demographics, characteristics of hip OA, and 10 markers: N-propeptides of collagen types I and III, cartilage oligomeric matrix protein, YKL-40, hyaluronan (sHA), matrix metalloproteinases-1 and -3, C reactive protein, C-terminal crosslinking telopeptides of collagen types I and II (uCTX-II). Radiographs were obtained at entry and every year. Structural progression was defined as a joint space decrease > or =0.5 mm or requirement for total hip replacement. Grouped survival analysis was performed with time to structural progression as dependent variable, and clinical data, radiographic findings, treatment groups (diacerein versus placebo), and markers as explanatory measures. RESULTS: In the 333 patients in whom all markers were measured, high functional impairment, a joint space width <2 mm, and lateral migration of the femoral head at baseline increased the risk of progression, but diacerein had a protective effect (relative risk = 0.75; 95% confidence interval (CI) 0.54 to 0.96). In addition, patients in whom uCTX-II and sHA were in the upper tertile had a relative risk of progression of 3.73 (95% CI 2.48 to 5.61) compared with patients with markers in the two lower tertiles. CONCLUSION: In this large cohort, combined measurements of uCTX-II and sHA were a new predictor of the structural progression of hip OA.

Aged↗

Long-term evolution of lymphocytes subsets after induction therapy based on continuous versus discontinuous administration of anti-thymocyte globulins in renal-transplant patients.

UNLABELLED: The aim of our retrospective study was to assess the long-term evolution of lymphocyte subsets after two modes of administration of anti-thymocyte globulin (ATG) after renal transplantation. METHODS: Before 1993, patients (group I, n = 93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days. Thereafter, RATG was either continued at the same dose for 15 days, in cases of delayed graft function, or was infused every other day at the same dose until the serum creatinine level became <150 micromol/L. After 1993, patients (group II, n = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and, thereafter, doses were adapted to target a CD2 T-cell count <50/mm3. RATG cumulative dose was significantly higher among group I than group II (9.7 +/- 4.5 versus 7.4 +/- 3.2 mg/kg, P = .0002). RESULTS: In both groups, total lymphocyte and T lymphocyte subset (CD4, CD8, CD2, CD3) counts decreased significantly during the first month after transplantation, increasing slowly between the first month and the third year posttransplantation. Thereafter it rose rapidly, which was greater in group II. At last follow up, total lymphocyte, T lymphocyte subsets and NK cell counts were similar to those observed before transplantation. At all monitoring times, T lymphocyte, B lymphocyte, and NK cell counts were similar in both group, except for the total lymphocyte count at 6 months and CD4 T lymphocyte count at 1 year, which were significantly higher in group II compared to group I. CONCLUSION: Induction therapy based on continuous or discontinuous administration of ATG is associated with profound depletion of T, B, and NK cells during the first 3 years, followed by a progressive reconstitution of the lymphocyte pool after 5 years.

Antigens, CD↗

A third renal transplantation: is it relevant and is it worth it?

INTRODUCTION: The aim of this retrospective study was to determine the outcome of third cadaveric renal transplantations performed between 1989 and 2004 among a cohort of 35 patients whose immunosuppression included induction therapy and calcineurin inhibitors. Most patients were highly sensitized with 1 (0-4) HLA (classes I + II) incompatibility between donor and recipient. RESULTS: The median follow-up time was 57 months (range, 1-190). Fourteen patients experienced delayed graft function that required posttransplantation hemodialysis. The current patient and graft survival rates were 91.4% and 82.8%, respectively. At last follow-up, 6 grafts had been lost: 1 due to primary nonfunction; 1 due to an urinary leak (day 45); 2 deaths with functioning grafts; and 2 chronic allograft nephropathies (CAN) at 85 and 60 months posttransplantation, respectively. Among the 10 patients who experienced acute rejection episodes, half were steroid-sensitive, whereas the others required OKT3 therapy. Overall, when excluding the 2 patients who presented with early loss of their grafts, 13 of 33 patients (39.4%) developed CAN, which led to the graft loss in only 2 cases. The mean creatinine clearance was 57 +/- 23 mL/min at year 5. Of the 35 recipients, 12 (34.3%) developed graft/perigraft complications, among whom 10 (83.3%) required treatment. The most frequent complication was lymphocele (M = 4; 11.4%) or infections that led to rehospitalization (n = 17). CONCLUSION: Results from third transplantations were encouraging. Thus, despite the organ shortage, a third graft was worth it!

Adult↗

[Association between the A2 allele of the HLA system and age at onset of Alzheimer's disease].

OBJECTIVE: Alzheimer is a multifactor disease occurring in a sensitive genetic territory. The e4 allele of the apolipoprotein E (APO E) is a recognised factor of risk. Some studies have suggested an association between the A2 allele of the HLA system and an earlier onset of the disease notably when it appears before the age of 64 or after the age of 75. The aim of our study was to explore this hypothesis in an independent sample of patients. METHODS: We compared the influence of the A2 allele of the HLA system on the age at onset of the disease in two groups of Caucasian patients presenting with Alzheimer's disease: early onset if the disease appeared before the age of 60 (n= 31) and late onset if it had appeared after the age of 75 (n= 44). The influence of the e4 allele of APO E was also taken into account. RESULTS: The comparison of the patients depending on the presence or not of at least one HLA-A2 allele revealed no significant difference, whatever the group of patients studied, in the age at onset of the disease. CONCLUSION: The age at onset of Alzheimer's disease was not influenced in our study by the presence of the HLA-A2 allele.

Age Factors↗

Use of prick-tests in the screening of immediate allergy to protein: 16 cases.

BACKGROUND: Allergy to protein hydrolysates seem to be on the rise but screening is difficult because of the wide range of symptoms. The goal of our study was to improve the screening process by skin prick testing infants with an anaphylactic form of allergy to cow's milk. METHODS: We studied 92 infants who were allergic to cow's milk. The diagnosis was based on the results of skin prick tests, specific IgE assays, and oral food challenges. The skin prick tests were performed using a number of protein hydrolysate formulae and a synthetic amino acid-based formula available in France. RESULTS: We detected sensitisation to the hydrolysates in 16 infants (17.3%), 15 by positive skin prick tests and one due to persistent symptoms on protein hydrolysate formulae (gastrointestinal manifestations, atopic dermatitis, and multiple food allergies), which completely receded when the synthetic amino acid formula was used as a substitute. Two infants had a positive hydrolysate oral food challenge test. There were no statistically significant differences in terms of age, sex, breastfeeding, clinical manifestations, family history, skin reaction size, or associated allergies. The infants who were sensitised to the hydrolysates had significantly higher specific IgE levels (whole milk,(_)-lactalbumin, and casein; median = 25.6 kU/L for cow's milk, p = 0.03) than those who were allergic to cow's milk but not sensitised to the hydrolysates. CONCLUSIONS: Skin prick tests can be used to screen for sensitisation to hydrolysates in infants with IgE-mediated cow's milk allergy. They can also be used to determine the most suitable hydrolysate formula for individual infants.

Administration, Oral↗

Interferon gamma gene polymorphism and susceptibility to, and severity of, rheumatoid arthritis.

A strong association between an interferon gamma (IFN-gamma) gene polymorphism and rheumatoid arthritis susceptibility and severity has been reported in a case-control study. We investigated this polymorphism in 103 patients with early rheumatoid arthritis and 130 controls. Severity of rheumatoid arthritis was measured after 4-year follow-up with a validated radiographic score. The median radiographic score in patients increased from 1 (IQR 0-4) to 11.5 (2-35) over the 4-year follow up. The distribution of IFN-gamma alleles did not differ between patients and controls, and the distribution of radiographic scores did not differ among patients carrying the different IFN-gamma alleles. We have failed to confirm the association between the IFN-gamma gene polymorphism and rheumatoid arthritis susceptibility or severity.

Alleles↗

[Kidney transplantation. Results and indications].

Results of renal transplantation are better than those of dialysis. The indications of transplantation are constantly increasing and comprise more and more populations at risk, notably older patients and diabetics. Specific evaluation of such potential recipients can lead to indication for transplantation and registry on the waiting list. The insufficient number of available cadaver kidneys leads to harvesting borderline organs particularly from the elderly or patients with vascular disease. Before definite decision for transplantation is made, case-by-case evaluation has to be made of the potential risks of donor-recipient matching regarding the risk/benefit for the recipient. Only a significant increase in the number of available organs will relieve the constraints of the problem.

Adult↗

Value of investigation in the diagnosis of allergic fungal rhinosinusitis: results of a prospective study.

The authors report a prospective study in which the aim was to analyse the usefulness of different criteria in optimizing the diagnosis of allergic fungal rhinosinusitis. From 1995 to 1998, 165 patients were operated on for chronic rhinosinusitis. Investigations used in this study for the diagnosis of allergic Aspergillus rhinosinusitis consisted of an analysis of clinical, radiological, immuno-allergic criteria. Fourteen patients presented with allergic Aspergillus rhinosinusitis. One hundred and fifty-one patients did not present any of the necessary criteria for the diagnosis of allergic Aspergillus rhinosinusitis. The results show that the characteristic macroscopic appearance, the maxillary sinus localization, and the presence of positive specific IgE to Aspergillus fumigatus are arguments that reinforce the diagnostic certitude of allergic fungal sinusitis. No specific clinical or radiological criteria orients a diagnosis of chronic rhinosinusitis toward that of allergic fungal rhinosinusitis. The other immuno-allergic tests do not contribute to the diagnosis of allergic fungal rhinosinusitis. pathological, mycological, and

Adolescent↗

Head-down tilt bed rest and immune responses.

Head-down tilt bed rest (HDT) is used as a model for studying the physiological changes occurring in weightlessness during spaceflight. In the present study, eight volunteers were subjected to a strict HDT of -6 degrees for 42 days. Blood samples were obtained 37 and 13 days before, at days 13, 34, and 41 during, and 12, 33, and 47 days after HDT. FACScan analysis was used to determine cell subpopulations. Plasma was used to quantify various circulating hormone levels. Whole blood and reconstituted blood were stimulated with various activators such as phytohaemagglutinin-P (PHA), PHA combined with phorbol-12-myristate 13-acetate (PMA), anti-CD2, anti-CD3, and lipopolysaccharide. Supernatants were collected and analysed for the interleukins IL-1beta, IL-2, IL-6, and IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). The total number of T lymphocytes and monocytes did not change significantly, whereas the number of polymorphonuclear cells increased during HDT. The percentage of CD2+ and CD3+ cells was increased at day 35 of HDT. The percentage and total number of natural killer cells (CD2+/CD3-/CD56+) was increased 12 days before and 14 days after HDT. TNF-alpha secretion did not change significantly during HDT. IL-2, IL-10 and IFN-gamma were increased at day 34 of HDT. IL-1beta levels were increased before and during HDT compared to post-HDT measurements. No significant changes were observed in plasma immunoglobulin, complement factors and other factors of the inflammatory system. Prolactin levels increased slightly but significantly at day 35 of HDT, thyreotropin and growth hormone levels remained virtually unchanged. Cortisol decreased slightly but significantly over the entire duration of the study. The changes observed during HDT do not indicate that the immune system is blunted, and these changes do not seem to correlate with the duration of HDT. Taken together these results show that a HDT does not reproduce the changes in immune responses observed after spaceflight.

Bed Rest↗

Relationship between the fatty acid composition of rat lymphocytes and immune functions.

The effects of dietary lipids on the fatty acid composition, activation and proliferation of lymphocytes were investigated. Weanling male Wistar rats were fed for 8 weeks on one of two low-fat diets which contained 50 g lipid/kg, or one of two high-fat diets containing 200 g lipid/kg, from either coconut oil or soyabean oil. The fatty acid composition of phospholipids from splenocyte membranes was affected by dietary lipid manipulation, and these differences influenced lymphocyte functions. Increased levels of linoleic acid in spleen lymphocytes correlated negatively with interleukin-2 receptor alpha-chain expression determined either by measuring the mean fluorescence or by the proportion of cells staining positive for CD25, and with the cell proliferation index. However, we found a positive correlation between interleukin-2 receptor alpha-chain expression determined by measuring the mean fluorescence and the cell proliferation index with the oleic acid concentration of spleen lymphocytes. Since phospholipid hydrolysis occurs early in lymphocyte activation, immunosuppressive effects induced by polyunsaturated fatty acids, described in the literature, could be due to an increase of linoleic acid or a decrease of oleic acid affecting many components of plasma-membrane-associated events involved in lymphocyte activation.

Animals↗

Mustard allergy in children.

BACKGROUND: Mustard allergy is not well known. This study aimed to assess its clinical features and other associated allergies, and to define skin prick tests (SPT), specific IgE, and dose response by oral food challenge. METHODS: Our study investigated 36 children with positive mustard SPT. The diagnosis of mustard allergy was based on open or single-blind, placebo-controlled food challenge (SBPCFC). We compared the subjects to 22 controls. RESULTS: The initial clinical features were atopic dermatitis (51.8%), and urticaria and/or angioedema (37%). Fifteen children were allergic (positive SBPCFC) and 21 children were nonallergic (negative SBPCFC). Symptoms after mustard ingestion started under 3 years of age in 53.3% of the subjects. There was no significant difference in the food allergies and associated inhalant allergen sensitizations between the two groups. In the allergic group, the mean wheal diameter for mustard SPT was 8.8 mm and the median concentration of mustard serum (s) IgE 14.8 kU/l. The mean cumulative reactive dose were 153 mg. CONCLUSIONS: Allergic reactions to mustard started early in life. Clinical symptoms were not severe in children. Mustard should be included in screening tests of food allergy in children.

Adolescent↗

Study of host- and virus-related factors associated with spontaneous hepatitis C virus clearance.

Epidemiologic parameters, virologic characteristics and frequency of HLA class II DR and DQ antigens were compared between 63 subjects with spontaneous hepatitis C virus clearance (group 1) and 282 patients with chronic active hepatitis C virus infection (group 2). DRB1*1101 and moreover DQB1*0301 alleles were more frequent in group 1 than in group 2 (33.8% vs. 14.7% and 64.4% vs. 28.6%; P=0.012 and P=0.003, respectively). The frequency of DQB1*02 was lower in group 1 than in group 2 (25.4% vs. 49%; P=0.04). No difference was observed in viral genotype distribution between group 1 and group 2. Univariate analysis showed that female sex and contamination by intravenous drug use were associated with self limited infection. However, by multivariate analysis, the only independent factor associated with hepatitis C virus RNA clearance was female sex (P=0.004). In conclusion, spontaneous hepatitis C virus RNA clearance is determined by class II antigens (mainly DQB1*0301) and female sex, while viral genotype plays no role.

Adult↗

Kinetics of intracytoplasmic Th1 and Th2 cytokine production assessed by flow cytometry following in vitro activation of peripheral blood mononuclear cells.

BACKGROUND: Standard cytokine detection methods are unable to determine which cells are the producing cells. We report on the extent and under which conditions the multilabeling capability of flow cytometry (FCM) can bring new advances into the field. METHODS: Five different cytokines, interleukin-2 (IL-2), -4, -5, -10 and interferon-gamma (IFN-gamma), were assessed simultaneously under five ex vivo stimulation conditions in peripheral blood mononuclear cells from five healthy volunteers in a 5-day kinetic study. A second group of 35 volunteers was assessed for IFN-gamma and IL-2 production. RESULTS: This study showed that (a) intracytoplasmic cytokines were almost undetectable within unstimulated cells, (b) intracytoplasmic cytokines were detected only in CD69(+) T lymphocytes, and (c) intracytoplasmic IL-2 and IFN-gamma were dramatically upregulated after stimulation with phorbol myristate acetate (PMA)-ionomycin in a biphasic response or with PMA-phytohemagglutinin (one major peak only at 18 h) but to a lesser extent with other stimuli such as monoclonal antibodies. Th2 cytokines were detected at a later time point and at lower levels. PMA/ionomycin stimulation after 4 h and 18 h of culture in 35 other volunteers individualized several subgroups according to the frequency of IFN-gamma- or IL-2-producing cells--IFN-gamma delayed producers (n = 10/35), IFN-gamma low producers (n = 8/35), and IL-2 delayed producers (n = 16/35)--as opposed to IFN-gamma or IL-2 normal producers. CONCLUSIONS: FCM appears to be a good tool to examine cell cytokine status in pathology (allergy, autoimmune disease, etc.) provided that optimal stimulation conditions and multiple time-point cultures are used. It also seems to be a relevant method to define new Th subsets further.

Antigens, CD↗

Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis.

OBJECTIVE: To test if interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in rheumatoid arthritis (RA). METHODS: The study included 108 patients with early RA followed up for 2 years and 128 healthy controls. From genomic DNA, 6 polymorphisms in genes for IL-1beta, IL-1Ra, IL-10, and IL-4 were typed. Allelic frequencies and carriage rates were compared between RA patients and controls, between patients with erosive and nonerosive RA, and between patients with or without sustained remission. RESULTS: The RP1 allele of the IL-4 gene was found with a significantly higher frequency in RA patients compared with controls. The combination of an RA-related HLA-DR allele expressing shared epitope and the presence of allele E2 in IL-1beta exon 5 was found to expose patients to an increased risk of erosive disease, with an odds ratio of 8.20 (95% confidence interval 2.59-25.84, P < 0.0001). No significant association was observed between polymorphisms and the occurrence of sustained remission. CONCLUSION: This report, for the first time, indicates an association between RA and a polymorphic IL-4 gene sequence located in 5q31-33. In addition, the results show the prognostic value of a polymorphism in IL-1beta exon 5, which allowed prediction of erosive disease with a specificity of 91.8% in 42.1% of patients. Although these observations are very interesting, they have to be considered preliminary and will need to be confirmed.

Arthritis, Rheumatoid↗