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Dive into the research topics where Alain Le Quellec is active.

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Featured researches published by Alain Le Quellec.


Arthritis & Rheumatism | 2013

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort.

Cloé Comarmond; Christian Pagnoux; Mehdi Khellaf; Jean-François Cordier; Mohamed Hamidou; Jean-François Viallard; F. Maurier; Stéphane Jouneau; Boris Bienvenu; Xavier Puéchal; O. Aumaître; Guillaume Le Guenno; Alain Le Quellec; Ramiro Cevallos; Olivier Fain; Bertrand Godeau; R. Seror; Alfred Mahr; P. Guilpain; P. Cohen; Achille Aouba; Luc Mouthon; Loïc Guillevin

OBJECTIVE Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long-term outcomes. METHODS A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis. RESULTS We identified 383 patients diagnosed between 1957 and June 2009 (128 [33.4%] before 1997 or earlier) and followed up for a mean±SD of 66.8±62.5 months. At diagnosis, their mean±SD age was 50.3±15.7 years, and 91.1% had asthma (duration 9.3±10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA-positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA-negative patients. Vasculitis relapses occurred in 35.2% of the ANCA-positive versus 22.5% of the ANCA-negative patients (P=0.01), and 5.6% versus 12.5%, respectively, died (P<0.05). The 5-year relapse-free survival rate was 58.1% (95% confidence interval [95% CI] 45.6-68.6) for ANCA-positive and 67.8% (95% CI 59.8-74.5) for ANCA-negative patients (P=0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse. CONCLUSION The characteristics and long-term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.


Human Mutation | 2000

MEFV mutations in Behçet's disease.

Isabelle Touitou; Xavier Magne; Nicolas Molinari; André Navarro; Alain Le Quellec; Paolo Picco; Marco Seri; Seza Ozen; Aysin Bakkaloglu; Ayşen Karaduman; Jean-Marc Garnier; Jacques Demaille; Isabelle Koné-Paut

Familial Mediterranean fever (FMF) and Behçets disease (BD), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations. FMF is a Mendelian autosomic recessive disease linked to MEFV, a gene of unknown function. BD in contrast is a polyfactorial disease associated with the major histocompatibility complex. Because FMF and BD have epidemiological similarities, we asked whether the FMF gene was implicated in BD. We screened for the common MEFV mutations a cohort of 114 chromosomes from definite BD patients [meeting the criteria of the International study group] and probable cases [meeting at least two of these criteria]. We screened in parallel an ethnically matched cohort of FMF and control chromosomes. The M694V, V726A and E148Q mutations tended to be more frequent in definite BD (2.6%, 2.6%, and 5.2%, respectively) than in controls (0%, 0%, and 2.2%). The P706 polymorphism was found in 10.5% of the probable BD chromosomes, but in only 1.6% of the controls (p=0.01). Because some MEFV mutations were more frequent in BD than in controls, we suggest that they may act as additional susceptibility factors in BD. Hum Mutat 16:271–272, 2000.


Annals of Pharmacotherapy | 2003

Adverse Drug Events Associated with Hospital Admission

Hélène Peyrière; Stéphanie Cassan; Edith Floutard; S. Rivière; Jean-Pierre Blayac; Dominique Hillaire-Buys; Alain Le Quellec; Sylvie Hansel

OBJECTIVE To increase the knowledge base on the frequency, causality, and avoidability of adverse drug events (ADEs) as a cause for admission in internal medicine or when occurring during hospitalization. METHODS A prospective study was performed for 6 periods of 8 days each. Epidemiologic data (e.g., age, gender, medical history), drug utilization, and adverse drug reactions on patients hospitalized during these periods were collected by a pharmacy student. RESULTS A total of 156 patients (70 men and 86 women) were included in the study. The patients’ mean age ± SD was 66.5 ± 18.1 years and mean length of stay was 13.2 ± 9 days. Renal and hepatic insufficiency and previous history of drug intolerance were observed in 17.9%, 10.2%, and 2% of the hospitalized patients, respectively. Thirty-eight ADEs occurred in 32 patients; in 15 cases, ADEs were identified as the reason for admission, 10 cases occurred during hospitalization, and 13 cases were present at admission, but were not the cause of admission. The most frequent ADEs involved the neurologic (23.6%), renal (15.7%), and hematologic (13.1%) systems. Among these 38 ADEs, 22 were considered avoidable (57.9%); 20 of these were associated with therapeutic errors (inappropriate administration, drug–drug interactions, dosage error, drug not stopped despite the onset of ADEs). Patients with ADEs stayed longer in the hospital and took more drugs both before and during their hospital stay (p < 0.05). CONCLUSIONS Most of the ADEs observed in this study were avoidable. The risk/benefit ratio of administered drugs could be improved with better knowledge of the patients’ medical history and the risk factors of ADEs.


Arthritis & Rheumatism | 2015

The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

Marie Jachiet; B. Flageul; Alban Deroux; Alain Le Quellec; F. Maurier; Florence Cordoliani; Pascal Godmer; C. Abasq; Leonardo Astudillo; P. Belenotti; D. Bessis; Adrien Bigot; M.-S. Doutre; M. Ebbo; Isabelle Guichard; E. Hachulla; Emmanuel Héron; Géraldine Jeudy; N. Jourde-Chiche; D. Jullien; C. Lavigne; L. Machet; Marie‐Alice Macher; Clotilde Martel; Sara Melboucy-Belkhir; Cécile Morice; Antoine Petit; Bernard Simorre; Thierry Zenone; Laurence Bouillet

Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.


Journal of Autoimmunity | 2016

Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.

Alexandre T. J. Maria; Karine Toupet; Marie Maumus; Guillaume Fonteneau; Alain Le Quellec; Christian Jorgensen; P. Guilpain; Danièle Noël

OBJECTIVES Displaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC). METHODS HOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs. RESULTS Xenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues. CONCLUSIONS Using primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients.


Arthritis & Rheumatism | 2016

Antifibrotic, Antioxidant, and Immunomodulatory Effects of Mesenchymal Stem Cells in HOCl-Induced Systemic Sclerosis.

Alexandre T. J. Maria; Karine Toupet; Claire Bony; Nelly Pirot; Marie-Catherine Vozenin; Benoit Petit; Pascal Roger; Frédéric Batteux; Alain Le Quellec; Christian Jorgensen; Danièle Noël; P. Guilpain

Systemic sclerosis (SSc) is a rare intractable disease with unmet medical need and fibrosis‐related mortality. Absence of efficient treatments has prompted the development of novel therapeutic strategies, among which mesenchymal stem cells/stromal cells (MSCs) or progenitor stromal cells appear to be one of the most attractive options. The purpose of this study was to use the murine model of hypochlorite‐induced SSc to investigate the systemic effects of MSCs on the main features of the diffuse form of the disease: skin and lung fibrosis, autoimmunity, and oxidative status.


Arthritis & Rheumatism | 2015

Brief Report: Childhood-Onset Systemic Necrotizing Vasculitides: Long-Term Data From the French Vasculitis Study Group Registry.

Michele Iudici; Xavier Puéchal; Christian Pagnoux; Pierre Quartier; Christian Agard; Achille Aouba; Matthias Büchler; Ramiro Cevallos; P. Cohen; Claire de Moreuil; Philippe Guilpain; Alain Le Quellec; P. Roblot; Jacques Serratrice; Claude Bachmeyer; Eric Daugas; Benjamin Terrier; Luc Mouthon; Loïc Guillevin

To describe the initial features and long‐term outcomes of childhood‐onset small vessel and medium vessel systemic necrotizing vasculitides (SNVs), including antineutrophil cytoplasmic antibody–associated vasculitides (AAVs) and polyarteritis nodosa (PAN).


Haematologica | 2010

The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance

Patricia Aguilar-Martinez; Michael Bismuth; F. Blanc; Pierre Blanc; Séverine Cunat; Olivier Dereure; Pierre Dujols; Muriel Giansily-Blaizot; Christian Jorgensen; A. Konaté; Dominique Larrey; Alain Le Quellec; Thibault Mura; Isabelle Raingeard; Eric Renard; Florence Rousseau; Jean-François Schved; Marie-Christine Picot

Background Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting. Design and Methods A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period. Results A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined. Conclusions A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible.


Journal of Crohns & Colitis | 2013

Pulmonary cryptococcosis in a patient with Crohn's disease treated with prednisone, azathioprine and adalimumab: Exposure to chicken manure as a source of contamination

J.-B. Fraison; P. Guilpain; Aurélie Schiffmann; Michel Veyrac; Vincent Le Moing; Philippe Rispail; Alain Le Quellec

BACKGROUND Biotherapies targeting TNFα were proven to be effective in the most severe cases of Crohns Disease, a chronic granulomatous inflammatory bowel disease that can involve any portion of the digestive tract. The tolerance of anti-TNFα therapy is usually good, although several infectious complications have been reported with these drugs. METHODS We report a case of a Crohns disease patient who developed pulmonary cryptococcosis following chicken manure exposition while he received adalimumab and azathioprine. CASE A 54-year-old man, with history of severe Crohns disease and ankylosing spondylitis, was admitted for diarrhea and abdominal pain under azathioprine treatment. In December 2010, he was treated with oral prednisone (1 mg/kg/day), but Crohns disease relapsed when prednisone dose was lower than 30 mg/a day. The patient was then treated with adalimumab, but six weeks later he developed severe pulmonary cryptococcosis. The patient experienced a good outcome under antifungal therapy. We retrospectively found a high exposure to chicken manure in the last weeks. CONCLUSION Cryptococcosis is an opportunistic infection that can occur under anti-TNFα therapy. The environmental exposure to Cryptococcus spp. (in particular in chicken manure) is a source of contamination. Avoiding exposition to bird manure should be a recommendation for patients who are living in rural areas.


Clinical Reviews in Allergy & Immunology | 2017

Adipose-Derived Mesenchymal Stem Cells in Autoimmune Disorders: State of the Art and Perspectives for Systemic Sclerosis.

Alexandre T. J. Maria; Marie Maumus; Alain Le Quellec; Christian Jorgensen; Danièle Noël; Philippe Guilpain

Mesenchymal stromal/stem cells (MSC) are non-hematopoietic multipotent progenitor cells, first described in bone marrow in the middle of last century. Since then, MSC have been the objects of a myriad of publications, progressively increasing our knowledge on their potentialities and bringing high expectancies for their regenerative properties. During the same period, numerous tissues, such as adipose tissue, placenta, or umbilical cord, have been used as alternative sources of MSC in comparison with bone marrow. In particular, considering the accessibility and ease to harvest fat tissue, adipose-derived MSC have gained interest above bone marrow-derived MSC. More recently, the discovery of MSC immunomodulatory properties made MSC-based therapy progressively slip from the field of regenerative medicine to the one of autoimmunity. Indeed, in this group of disorders caused by aberrant activation of the immune system resulting in loss of self-tolerance and auto-reactivity, conventional immunosuppressant may be harmful. One advantage of MSC-based therapy would lie in their immune plasticity, resulting in space and time-limited immunosuppression. More specifically, among autoimmune disorders, systemic sclerosis appears as a peculiar multifaceted disease, in which autoimmune phenomena coexist with vascular abnormalities and multi-visceral fibrosis. Considering the pleiotropic effects of MSC, displaying immunomodulatory, angiogenic and antifibrotic capabilities, MSC-based therapy could counteract the three main pathogenic axes of systemic sclerosis and might thus represent a complete breakthrough in this intractable disease with unmet medical need. In this article, while reviewing most recent literature on MSC biology, we itemize their current applications in the field of autoimmunity and shed light onto the potential use of adipose-derived MSC as an innovative strategy to cure systemic sclerosis.

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P. Guilpain

University of Montpellier

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S. Rivière

University of Montpellier

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Loïc Guillevin

Paris Descartes University

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Xavier Puéchal

Paris Descartes University

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Benjamin Terrier

Paris Descartes University

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Danièle Noël

University of Montpellier

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