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

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Morgand, Marjolaine | Buffet, Marc | Busson, Marc | Loiseau, Pascale | Malot, Sandrine | Amokrane, Kahina | Fortier, Catherine | London, Jonathan | Bonmarchand, Guy | Wynckel, Alain | Provôt, François | Poullin, Pascale | Vanhille, Philippe | Presne, Claire | Bordessoule, Dominique | Girault, Stéphane | Delmas, Yahsou | Hamidou, Mohamed | Mousson, Christiane | Vigneau, Cécile | Lautrette, Alexandre | Pourrat, Jacques | Galicier, Lionel | Azoulay, Elie | Pène, Frédéric | Mira, Jean-Paul | Rondeau, Eric | Ojeda-Uribe, Mario | Charron, Dominique | Maury, Eric | Guidet, Bertrand | Veyradier, Agnès | Tamouza, Ryad | Coppo, Paul | Center, Thrombotic Microangiopathies Reference

Edité par CCSD ; Wiley -

National audience. 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. STUDY DESIGN AND 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 \textless 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. CONCLUSION: 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.

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