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A Saraux, J Jouquan,
P Le Goff,
P Youinou,
Y Levy,
J C Piette,
L Guillevin,
G Semana,
D Salmon,
J P Viard,
J F Bach,
Y Shoenfeld
Arthritis & Rheumatism 06/1999; 42(5):1062-4. · 7.87 Impact Factor
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ABSTRACT: As part of preparations for the first seminar in general practice, organized for medical students in their forth year at the Brest faculty of medicine, students were asked to fill in a questionnaire concerning their beliefs and knowledge concerning general-practice medicine. Fifty-two students, or 89.6% of the class, completed the questionnaires. The results showed that despite the lack of formal contacts with this type of practice during their studies, the students had a good idea of what general-practice medicine is and of the role of the general practitioner in our health-care system. However, this study has illustrated the difficulties students experience in defining their future professional direction, since they receive no information during their training on the different options in medical practice.
Santé Publique 07/1997; 9(2):207-20. · 0.24 Impact Factor
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ABSTRACT: Our objective was to study the interaction between major histocompatibility complex (MHC) class II and T-cell receptor (TCR) alleles in the recognition of extractable nuclear antigen-derived peptides in 32 patients with systemic lupus erythematosus and 173 of their family members. MHC genes were analyzed using sequence specific oligonucleotides, and TCR beta-chain gene polymorphism using restriction fragment-length polymorphism. One dominant peptide (as defined by enzyme-linked immunosorbent assay autoantibody reactivity) was identified in each antigen studied: peptide 1-20 in Sm-D, peptide 35-58 in U1-RNP-A, and peptide 304-324 in the Ro/SSA 60 Kd protein. None of the MHC class II and TCR beta haplotypes was directly associated with any of the autoantibodies. Twenty-six subjects had antibodies to the peptide Sm-D1-20; nine of them were DRB1*0101/DQB1*0501. Among subjects with this haplotype, the number of responders was higher (p < 0.028, p corrected, pc = 0.336) in those with the 2-25-9 TCR beta haplotype than in the remainder. Conversely, the number of DRB1*04/DQB1*0302 responders was lower (p < 0.030, pc = 0.360) among subjects with the 23-20-9 TCR beta haplotype than in those without. The odds ratios (OR) were 4.23 and 0.21, respectively. Of the 54 subjects positive for anti-U1-RNP-A 35-38, 13 were DRB1*0101/DQB1*0501 and eight DRB1*04/DQB1*0302. The percentage of responders was higher (p < 0.041, pc = 0.492, OR = 3.48) in the former group of subjects with the 2-25-9 TCR beta haplotype, and lower (p < 0.02, pc = 0.024, OR = 0.09) in the latter with the 23-20-9 TCR beta haplotype. Three of the 12 anti Ro/SSA 60Kd 304-324-positive subjects were DRB1*0101/DQB1*0501. All had the 2-25-9 TCR beta haplotype (p < 0.046, pc = 0.552, OR = 6.29) and none the 23-20-9 (p < 0.031, pc = 0.372, OR = 0.10). The same combinations of genes were associated with high/low response toward the three peptides. These data provide evidence for an interplay of the MHC class II and TCR beta alleles in the control of specific autoantibody response to well-defined nuclear Ag peptides.
Human Immunology 02/1997; 52(1):12-21. · 2.84 Impact Factor
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P Youinou,
D A Isenberg,
J K Kalsi,
J M Dugoujon,
C T Ravirajan,
S Muller,
F Blanco,
J C Piette,
L Guillevin, J Jouquan,
G Semana,
D Salmon,
Y Shoenfeld,
J F Bach
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ABSTRACT: Our aim was to investigate links between systemic lupus erythematosus (SLE)-associated autoantibodies, idiotypes (Id) and genetic predisposition to their development. We studied four public Ids (16/6, WRI 176 beta, RT72 and RT84), identified the Km and Gm phenotypes and sought six selected autoantibodies in 32 SLE patients, 174 of their relatives and 15 spouses. Though anti-double-stranded DNA antibody was uncommon in the relatives (9%), the range of antinuclear reactivities was as broad in the relatives as in the probands. Antibodies to the synthetic peptide U1-RNP-A 35-38 were found in 56% of the patients, 28% of their relatives and 20% of the spouses, whereas antibodies to the Golgi apparatus was present in 7% of the patients, 26% of their relatives and 33% of the spouses. However, most of these family members were unaffected. RT84 Id was positively associated with antibodies to Sm-D peptide 1-20 and to Ro/SSA 60 kD peptide 304-324, but negatively associated with anti-dsDNA activity. The median of age was significantly lower in the RT84 Id-positive than in the RT84 Id-negative individuals. These data suggest that genetic as well as environmental factors are involved in the aetiology of SLE. In addition, RT84-carrying immunoglobulins (Ab2) might be directed to one of many cross-reactive Ids of dsDNA-binding antibodies (Ab1), perhaps down-regulating their production.
Journal of Autoimmunity 01/1997; 9(6):767-75. · 7.37 Impact Factor
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Journal Français d Ophtalmologie 02/1995; 18(11):708-13, 715-30. · 0.51 Impact Factor
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La Revue de Médecine Interne 02/1995; 16(1):76-7. · 0.61 Impact Factor
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ABSTRACT: Sera from patients with giant cell arteritis and/or polymyalgia rheumatica were tested for the presence of IgG, IgM and IgA antibody to endothelial cells (AEC), cardiolipin (ACL) and phosphatidylethanolamine (APE) using enzyme-linked immunosorbent assays. There were strong correlations between ACL and APE, but also between AEC and ACL IgM (p < 0.02) and between AEC and APE IgA (p < 0.003). Inhibition of AEC binding was achieved by absorption onto EC, but ACL and APE binding was also significantly reduced. In contrast, the binding of AEC antibody could not be inhibited by incubation with CL. Our data suggest that AEC constitute a heterogeneous population of autoantibodies.
Autoimmunity 01/1995; 20(1):59-66. · 2.47 Impact Factor
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ABSTRACT: Its was our aim to appreciate the respective influence of age, sex, duration of disease, inflammatory status and treatment on protein markers in patients with rheumatoid arthritis (RA). Serum albumin (SA), thyroxin-binding prealbumin (TBPA), transferrin and retinol-binding protein (RBP) were determined in 155 RA patients. Since the cut off, levels of these proteins are highly dependent on sex and age, several groups of sex- and age-matched normal controls were evaluated. The levels of SA (p < 0.03) and RBP (p < 0.002) were reduced in the women under 45 years of age. SA and RBP reached a nadir following one year of evolution. There were inverse correlations between SA and Lee's index (p < 0.01) and TBPA and Lee's (p < 0.05) and Ritchie's index (p < 0.01). Sa correlated inversely with the inflammatory status. The complex challenge of nutritional evaluation in RA patients is thus impossible to adequately portray and results should be interpreted with caution.
Annales de medecine interne 01/1995; 146(6):409-12.
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ABSTRACT: We report the case of an elderly woman with severe dysautonomic orthostatic hypotension in whom a deficit in dopamine B hydroxylase has been established. In the literature, such a deficit has been described in six young adults with long standing symptoms of postural hypotension. This enzyme catalyses the conversion of dopamine to noradrenaline. In our elderly patient, noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was detectable. Treatment with the synthetic amino acid, DL-threo-dihydroxyphenylserine, which is converted to noradrenaline by dopa-decarboxylase, resulted in a significant increase in blood pressure. The mechanism of this acquired deficit is not elucidated.
Journal of the American Geriatrics Society 06/1993; 41(5):550-1. · 3.74 Impact Factor
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ABSTRACT: The study of 30 patients with systemic lupus and of 153 relatives failed to show any differences in HLA and TCR beta haplotype frequencies between patients and relatives. A significant interaction between TCR V beta and HLA-DR/DQ genes in the response to the peptide U1-RNP A 35-58 was demonstrated.
La Revue de Médecine Interne 02/1993; 14(10):979. · 0.61 Impact Factor
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ABSTRACT: Anti-neutrophil cytoplasm antibodies (ANCA) were detected at low titers by indirect immunofluorescence in 1 out of 13 patients with giant cell arteritis (GCA) alone, 7 out of 30 with polymyalgia rheumatica (PMR) alone and 4 out of 15 with GCA plus PMR (8, 23 and 27%, respectively). Anti-myeloperoxidase antibodies were also demonstrated by an enzyme-linked immunosorbent assay in 4 patients with GCA alone (31%), 13 with PRM alone (42%) and 5 with GCA plus PRM (33%). The C-reactive protein response was significantly higher (p < 0.05) in ANCA-positive than in ANCA-negative patients.
Annales de medecine interne 02/1992; 143(7):429-32.
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ABSTRACT: Fifty-six human immunodeficiency virus-1-positive asymptomatic carriers were tested for the presence of a variety of nonorgan-specific autoantibodies. Antinuclear antibodies were detected in 34 sera, of which 27 were directed to the mitotic spindle apparatus and all were of the IgG isotype. Anti-Golgi complex, anti-centriole, and anti-vimentin antibodies were also present in 20.4, and 4 sera, respectively. Ten patients had less than 500 CD4-carrying T lymphocytes per cubic millimeter. Nine of them had more than one autoantibody. No correlation could be demonstrated between the number of autoantibodies and the level of serum immunoglobulins.
Clinical Immunology and Immunopathology 07/1991; 59(3):487-94.
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La Presse Médicale 04/1991; 20(12):564-5. · 0.67 Impact Factor
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ABSTRACT: IgA-, IgM- and IgG-containing immune complexes (CIC) were detected in 48, 19 and 12% of 52 patients with primary Sjögren's syndrome (SS), in 36, 38 and 56% of 45 patients with rheumatoid arthritis, and in 8, 5 and 3% of 40 normal controls. A high proportion of primary SS patients also had considerable amounts of serum IgA and elevated levels of IgA with rheumatoid factor (RF) activity. IgA-CIC and IgA-RF were more frequent (P less than 0.03 and less than 0.001) in the 27 primary SS patients with, than in the 25 without extraglandular manifestations. IgA-CIC could play a role in mediating the tissue injury associated with primary SS.
Journal of Autoimmunity 03/1991; 4(1):177-84. · 7.37 Impact Factor
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ABSTRACT: Twenty-five patients with idiopathic Raynaud's phenomenon were followed prospectively for a mean period of 48 months. Clinical and laboratory assessments were performed on admission and on followup. The sera were analyzed for the presence of autoantibodies (antinuclear, antiskeleton and antiorganelle antibodies). Sixteen patients were antinuclear antibody positive and 2 anticentromere antibody positive. Eight patients produced antivimentin, 5 antimitochondrial, 4 anti-Golgi complex, and 3 anticentriol antibodies. Eleven patients produced antidesmosome antibodies. Only one patient (anti-RNP and antidesmosome antibody positive) developed a systemic disease (mixed connective tissue disease) during followup. The initial screening of sera may help to classify Raynaud's phenomenon as idiopathic more accurately.
The Journal of Rheumatology 10/1990; 17(9):1177-81. · 3.69 Impact Factor
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ABSTRACT: Forty-five consecutive primary Sjögren's syndrome (SS) patients were divided into two subgroups according to the presence (n = 30) of Raynaud's phenomenon (RP). Non-erosive arthritis was significantly more frequent in the patients with RP than in those without. RP was not associated with HLA-DR4 in primary SS patients.
British journal of rheumatology 07/1990; 29(3):205-7.
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ABSTRACT: The influence of genetic factors on the expression of CD5+ B lymphocytes and their relationship to a broad spectrum of autoantibodies was investigated in a study of 12 patients with rheumatoid arthritis (RA) and 52 of their healthy first-degree relatives. The proportion of CD5+ B cells was significantly higher in RA patients (mean +/- SEM 23.9 +/- 2.7%) compared with that in their relatives (18.3 +/- 1.1%, P less than 0.05) and compared with that in a group of healthy control subjects (16.1 +/- 1.8%; P less than 0.05). Much more striking, however, were the high levels of CD5+ B cells found in the patients and their relatives in 5 of the families studied. Increases in total immunoglobulin levels and autoantibody levels were frequently observed in RA patients (approximately 20-40%) and their relatives (approximately 10-20%). Furthermore, a statistically significant correlation (P less than 0.01) between IgM rheumatoid factor and the percentage of B lymphocytes expressing CD5 was observed.
Arthritis & Rheumatism 04/1990; 33(3):339-48. · 7.87 Impact Factor
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ABSTRACT: This study was designed to compare labial and sublingual salivary gland biopsies in the diagnosis of Sjögren's syndrome (SS). Fourteen labial and 29 sublingual specimens were considered positive. There was a better correlation between infiltration of the ductal structure and the focus score in the sublingual salivary gland biopsy than in the labial salivary gland biopsy. Use of sublingual salivary gland biopsy as an additional diagnostic tool in SS is therefore suggested.
Annals of the Rheumatic Diseases 02/1990; 49(1):37-9. · 8.73 Impact Factor
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ABSTRACT: Cord blood and fetal liver B cells were immortalized using Epstein-Barr virus, and IgM antibodies from the resulting lines and clones were examined for their binding to a variety of auto-antigens and micro-organisms by ELISA and fluorescence assays. Auto-antigens tested included Fc of IgG, ssDNA and dsDNA, cardiolipin, histones 1-4, collagens type I and II, thyroglobulin, cytoskeletal components, and a tissue section screen. Of 71 cell lines tested, all but 19 showed some autoreactivity. All 32 fetal liver lines reacted to some self-antigens. In cord blood clones, 16 out of 26 bound to auto-antigens. Many of the clones reacted with more than one auto-antigen and were 'polyreactive'. Some of the cord blood clones bound to extracts of micro-organisms, showing specificity for both endogenous and exogenous antigens. The high frequency of CD5+ B cells in the cord blood (greater than 50%) and fetal liver (greater than 70%) argues for many of these clones being derived from this subset. Therefore, our data support the concept that many 'early' B cells produce polyreactive IgM which can bind to a variety of different auto-antigens and micro-organisms. These IgM antibodies are similar to those described by others as 'natural antibodies'.
Scandinavian Journal of Immunology 02/1990; 31(1):33-43. · 2.23 Impact Factor
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ABSTRACT: A broad range of autoreactivity among a group of 12 French patients with rheumatoid arthritis (RA) and 58 of their healthy first degree relatives has been identified. Over 15% of the patients were found to have antibodies to ssDNA, histone H1, H2A, and H2bB. Among the relatives, IgG and IgM rheumatoid factor and antibodies to ssDNA, H2A, and H4 were present in more than 10%. Even more remarkable, a common anti-DNA antibody idiotype designated PR4, known to be present in 70% of patients with systemic lupus erythematosus (SLE), was found in approximately 30% of both patients with RA and their healthy relatives. This is quite different from its lack of increased expression in relatives of patients with SLE and suggests that in the family members of those with RA a particular combination of environmental influence on germline gene expression is responsible.
Annals of the Rheumatic Diseases 12/1989; 48(11):898-904. · 8.73 Impact Factor