Association between mycophenolic acid treatment and infection with specific strains of Pneumocystis jirovecii in solid organ transplant recipients in France and Switzerland: a multicentre, retrospective, cross-sectional study
- Type de publi. : Article dans une revue
- Date de publi. : 01/09/2025
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Auteurs :
Claire V HoffmannYannick Le MeurMarie-Christine MoalAnne Grall-JézéquelNathan Le NanNicolas PaponGilles NevezSolène Le GalAnne TotetHakim MazouzJean-Philippe BoucharaVirginie BessonEmeline SchererDidier DuclouxKonrad MühlethalerPierre L BonnetJulie BonhommeThierry LobbedezValérie ChateletCéline NourrissonCyril GarrousteFrançoise BotterelMarie MatignonFrederic DalleClaire TinelDanièle Maubonjohan nobleBoualem SendidJordan LeroyFrançois ProvotMarie-Fleur DurieuxClément DanthuJean MenottiFrançois BaillyChristophe RavelMoglie Le QuintrecAnne DebourgogneMarc LadriereFlorent MorioMagali GiralLilia HasseineLaetitia AlbanoNicolas ArgyRichard DorentArnaud FekkarValérie PourcherEstelle CateauAntoine ThierryAntoine HugueninAlain WynckelFlorence Robert-GangneuxElsa VabretDamien CostaBertrand DominiquePierre FloriEmmanuelle TavernierJulie BrunetLaura BraunXavier IriartArnaud del BelloGuillaume DesoubeauxMatthias BuchlerNatalja KulaginaVincent Courdavault
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Organismes :
Hôpital de la Cavale Blanche - CHRU Brest
Centre Hospitalier Régional Universitaire de Brest
Infections Respiratoires Fongiques
CHRU Brest - Service de Nephrologie
Lymphocytes B, Autoimmunité et Immunothérapies
CHRU - Service de néphrologie, dialyse et transplantation rénale
CHRU Brest - Service de Nephrologie
Université de Brest
Infections Respiratoires Fongiques
SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques
SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques
Infections Respiratoires Fongiques
Infections Respiratoires Fongiques
Laboratoire de Parasitologie et Mycologiede [CHRU Brest]
Université de Brest
Université de Brest
Infections Respiratoires Fongiques
Laboratoire de Parasitologie et Mycologiede [CHRU Brest]
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294
CHU Amiens-Picardie
Unité de Transplantation Rénale et Pancréatique [CHU Sud, Amiens]
SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques
Infections Respiratoires Fongiques
Laboratoire de Parasitologie-Mycologie, CHU d'Angers, Angers,
Centre Hospitalier Universitaire d'Angers
Laboratoire Chrono-environnement (UMR 6249)
Service de parasitologie et mycologie [CHRU de Besançon]
Centre Hospitalier Régional Universitaire de Besançon
Service de Néphrologie [CHRU Besançon]
Université de Bordeaux
CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie
CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie
Centre Universitaire des Maladies Rénales [CHU Caen]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias
Service Néphrologie, Hémodialyses [CHU Clermont-Ferrand]
Dynamic Microbiology - EA 7380
Hôpital Henri Mondor
CHU Dijon
Institut Necker Enfants-Malades
Service Néphrologie et transplantation rénale Adultes [CHU Necker]
Centre Hospitalier Universitaire [CHU Grenoble]
Centre Hospitalier Universitaire [CHU Grenoble]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Centre Hospitalier Régional Universitaire [CHU Lille]
Service de Parasitologie-Mycologie [CHRU LIlle]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Centre Hospitalier Régional Universitaire [CHU Lille]
Université de Limoges
Service de Néphrologie, Dialyse, Transplantations [CHU Limoges]
Institut des Agents Infectieux [Lyon]
CHU Lyon
Centre Hospitalier Régional Universitaire [Montpellier]
Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
Department of Nephrology, Dialysis and Transplantation, Montpellier University Hospital
Centre Hospitalier Régional Universitaire de Nancy
Stress, Immunité, Pathogènes
Université Claude Bernard Lyon 1
Hospices Civils de Lyon
Cibles et Médicaments des Infections et de l'Immunité - UR 1155
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
Institut de Transplantation et de Recherche en Transplantation [CHU Nantes]
CHU Nice [Cimiez]
Département de Néphrologie - Hôpital Pasteur [Nice]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Agence de la biomédecine [Saint-Denis la Plaine]
CHU Pitié-Salpêtrière [AP-HP]
Institut Pierre Louis d'Epidémiologie et de Santé Publique
CHU Pitié-Salpêtrière [AP-HP]
Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
Ischémie reperfusion, métabolisme et inflammation stérile en transplantation [U 1313]
Université de Poitiers = University of Poitiers
Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
Service de néphrologie - hémodialyse et transplantation rénale [CHU Poitiers]
Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle
Hôpital universitaire Robert Debré [Reims]
Hôpital universitaire Robert Debré [Reims]
Institut de recherche en santé, environnement et travail
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Université de Rennes
École des Hautes Études en Santé Publique [EHESP]
Arènes: politique, santé publique, environnement, médias
Recherche sur les services et le management en santé
Université de Rouen Normandie
Département de Microbiologie [CHU Rouen]
UNIROUEN - UFR Santé
Service de Néphrologie [Rouen]
Service des Agents Infectieux et Hygiène [CHU Saint-Etienne]
Institut de Cancérologie de la Loire Lucien Neuwirth
Laboratoire de Parasitologie et de Mycologie Médicale [Strasbourg]
Pathogens Host Arthropod Vectors Interfaces
service de Néphrologie et Transplantation Rénale [CHU Strasbourg]
Centre Hospitalier Universitaire de Bordeaux
Institut Toulousain des Maladies Infectieuses et Inflammatoires
Centre Hospitalier Universitaire de Toulouse
Centre d’Etude des Pathologies Respiratoires [Tours]
Service de néphrologie et immunologie clinique [CHRU Tours]
Université de Tours
Biomolécules et Biotechnologies Végétales [Tours]
Biomolécules et Biotechnologies Végétales [Tours]
- Publié dans The Lancet Microbe le 11/12/2020
Résumé : Background: Pneumocystis pneumonia (PCP) case clusters involving solid organ transplant (SOT) recipients have been reported worldwide. Mycophenolic acid, an immunosuppressant used to prevent rejection in SOT recipients that targets the inosine 5 ′ -monophosphate dehydrogenase (IMPDH) protein, has been hypothesised to exert selective pressure on Pneumocystis jirovecii, with the missense mutation G1020A (Ala261Thr) in the impdh gene a possible marker of such selective pressure. The aim of this study was to test the hypothesis that SOT recipients harbour P jirovecii with mutations in the impdh gene and are infected with specific P jirovecii strains. Methods: In this retrospective, multicentre, cross-sectional study of nationally representative, individual-level data, we included SOT recipients, regardless of the organ transplanted, involved or not in a PCP case cluster, and non-SOT recipients (control group) without mycophenolic acid exposure, diagnosed with PCP from 26 French and one Swiss secondary health-care centres. We included patients aged 18 years or older for whom archival P jirovecii DNA extracts were available in sufficient quantity and quality. P jirovecii specimens were characterised using a multilocus sequence typing method including impdh gene analysis. The primary outcome of this study was the detection of the G1020A (Ala261Thr) mutation in the impdh gene. A multivariable logistic regression was done to assess the relation between this mutation and the following variables retrieved from medical records: age, mycophenolic acid exposure at the time of PCP diagnosis, involvement in a PCP case cluster, PCP prophylaxis, and clinical outcome. Findings: 58 SOT recipients (44 treated with mycophenolic acid) and 59 non-SOT recipients (control group; not treated with mycophenolic acid) diagnosed with PCP between Jan 1, 2001, and Dec 31, 2021, were enrolled. The G1020A (Ala261Thr) mutation was detected in P jirovecii specimens from 40 (68⋅9%) SOT recipients (37 treated with mycophenolic acid) and in none of the P jirovecii specimens from the patients in the control group. The multivariable analysis showed that the allele characterised by the G1020A mutation was associated with mycophenolic acid exposure at the time of PCP diagnosis (adjusted odds ratio 73⋅61 [95% CI 17⋅41-455⋅70]; p<0⋅0001) and involvement in a PCP case cluster (12⋅77 [1⋅58-171⋅90]; p=0⋅029), whereas it was not associated with age, PCP prophylaxis, and clinical deterioration. A second missense mutation, G1020T (Ala261Ser) was identified in P jirovecii specimens from three SOT recipients (two treated with mycophenolic acid). Two specific multilocus genotypes (MLG-31 and MLG-34) of P jirovecii associated with Ala261Thr and Ala261Ser substitutions in IMPDH, respectively, were detected only in SOT recipients (38 patients with MLG-31 and three patients with MLG-34). Interpretation SOT recipients in this study were primarily infected with specific P jirovecii strains with mutations in the impdh gene, which might confer a selective advantage as both the G1020A (Ala261Thr) and G1020T (Ala261Ser) are associated with mycophenolic acid resistance in other fungi. Mycophenolic acid selective pressure might explain the maintenance and circulation of these P jirovecii strains within this patient population, and consequently their potential involvement in PCP case clusters.
Fichiers liés :
Hoffmann et al. Lancet Microbe, 2025.pdf
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