title: High prevalence of infectious events in thrombotic thrombocytopenic purpura and genetic relationship with toll-like receptor 9 polymorphisms: experience of the French Thrombotic Microangiopathies Reference Center.
abstract: BACKGROUND
  Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP.
  
  
  METHODS
  We recruited randomly and prospectively a cohort of 280 consecutive TTP patients during a 9-year period. Features of infection were systematically recorded.
  
  
  RESULTS
  Features consistent with an infectious event were observed in 114 patients (41%) at time of TTP diagnosis. Infectious agents were documented in 34 cases and were mainly Gram-negative bacilli. At time of diagnosis infected patients more frequently had fever (p < 0.001). Infections at diagnosis did not impact prognosis and outcome. Thirty-six percent of patients experienced an infectious event during hospitalization, which resulted in more exacerbation of TTP (p = 0.02). Infections were not overrepresented during treatment in patients who received steroids and/or rituximab. Further genetic analysis of toll-like receptor (TLR)-9 functionally relevant polymorphisms revealed that TLR-9 +2848 G and TLR-9 +1174 A genotypes were more frequent in TTP patients than in controls (p = 0.04 and p = 0.026, respectively) and more particularly in patients negative for the Class II human leukocyte antigen system susceptibility allele DRB1*11 (p = 0.001 and p = 0.002, respectively). Haplotypes estimation showed that 1174A-2848G haplotype was significantly more frequent in TTP (p = 0.004), suggesting a primary role for this haplotype variation in conferring a predisposition for acquired TTP.
  
  
  CONCLUSIONS
  Infections should be considered as an aggravating factor during the course of TTP. Particular polymorphisms in TLR-9 gene may represent risk factors for TTP.
authors.affiliation: Service d'Hématologie, Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris, France; Service de Réanimation Polyvalente, Hôpitaux Universitaires de l'Est Parisien, AP-HP et UPMC Univ Paris 06, Paris, France; Inserm U1009, Institut Gustave Roussy, Villejuif, France; Laboratoire Jean Dausset d'Immunologie et d'Histocompatibilité & INSERM, AP-HP, UMRS 940, Paris, France; Service d'Immunopathologie, Service de Réanimation, Hôpital Saint-Louis, Université Paris 7 Denis Diderot, Paris, France; Service de Réanimation Médicale, Hôpital Charles Nicolle, Rouen, France; Service de Néphrologie, Hôpital Maison Blanche, Reims, France; Service de Néphrologie, Centre Hospitalier Universitaire, Lille, France; Service d'Hémaphérèse, Service de Médecine Interne, Hôpital de la Conception, Marseille, France; Service de Néphrologie, Centre Hospitalier de Valenciennes, Valenciennes, France; Service de Néphrologie- Médecine Interne, Hôpital Sud, Amiens, France; Service d'Hématologie Clinique et de Thérapie Cellulaire, CHU Dupuytren, Limoges, France; Service de Néphrologie, Hôpital Pellegrin, Bordeaux, France; Service Médecine Interne A, Hôpital Hôtel-Dieu, Nantes, France; Service de Néphrologie, Dijon, France; Service de Néphrologie, Hôpital Pontchaillou, Rennes, France; Service de Réanimation Médicale (7HO), Hôpital Gabriel Montpied, Clermont-Ferrand, France; Service de Néphrologie et Immunologie Clinique, CHU Rangueil, Toulouse, France; Service de Réanimation Polyvalente, AP-HP, Hôpital Cochin, Université Paris 5, Paris, France; Service de Réanimation Néphrologique, Hôpital Tenon, UPMC Université Paris 06, Paris, France; Service d'Hématologie, Hôpital Emile Muller, Mulhouse, France; Service d'Hématologie Biologique, Hôpital Antoine Béclère, AP-HP, Clamart et Université Paris-Sud 11, Le Kremlin-Bicêtre, France.
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Morgand
authors.forename: Marc
authors.initials: M
authors.lastname: Buffet
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Pascale
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authors.lastname: Loiseau
authors.forename: Sandrine
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authors.lastname: Malot
authors.forename: Kahina
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authors.lastname: Amokrane
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortier
authors.forename: Jonathan
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authors.lastname: London
authors.forename: Guy
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authors.lastname: Bonmarchand
authors.forename: Alain
authors.initials: A
authors.lastname: Wynckel
authors.forename: François
authors.initials: F
authors.lastname: Provôt
authors.forename: Pascale
authors.initials: P
authors.lastname: Poullin
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhille
authors.forename: Claire
authors.initials: C
authors.lastname: Presne
authors.forename: Dominique
authors.initials: D
authors.lastname: Bordessoule
authors.forename: Stéphane
authors.initials: S
authors.lastname: Girault
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.forename: Christiane
authors.initials: C
authors.lastname: Mousson
authors.forename: Cécile
authors.initials: C
authors.lastname: Vigneau
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lautrette
authors.forename: Jacques
authors.initials: J
authors.lastname: Pourrat
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pène
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.forename: Mario
authors.initials: M
authors.lastname: Ojeda-Uribe
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Eric
authors.initials: E
authors.lastname: Maury
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
mesh_terms: D000328:Adult; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007239:Infections / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology / Q000235:genetics*; D012042:Registries; D012307:Risk Factors; D057049:Thrombotic Microangiopathies / Q000453:epidemiology / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9