Journal of thrombosis and haemostasis : JTH · 2026
Natural history of antiplatelet antibody formation in patients with Glanzmann thrombasthenia: a French multicenter prospective study.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Desprez Dominique, d'Oiron Roseline, Voisin Sophie, Falaise Céline, Alessi Marie-Christine, Saultier Paul, Lavigne Géraldine, Essaydi Arnaud, Apithy Marie-Joelle, Dupuis Arnaud, Goin Valérie, Huguenin Yoann, Fiore Mathieu
Аннотация
BACKGROUND: Glanzmann thrombasthenia (GT) is a rare inherited platelet function disorder caused by defects in the ITGA2B or ITGB3 genes encoding the αIIbβ3 integrin. Repeated transfusions often lead to immunization against αIIbβ3 and/or HLA antigens, compromising transfusion efficacy.
OBJECTIVES: This study aimed to prospectively characterize the development and evolution of anti-αIIbβ3 and anti-HLA antibodies in a large cohort of French patients with GT and to assess their potential functional effects on platelet activity.
METHODS: This multicenter prospective study included 55 patients with GT who were followed up between 2018 and 2025. Anti-αIIbβ3 antibodies were detected using monoclonal antibody-specific immobilization of platelet antigen assays, and anti-HLA antibodies were screened using the Luminex-based technology. Functional analyses included fibrinogen binding, CD62P exposure, and complement deposition on donor platelets.
RESULTS: Anti-αIIbβ3 antibodies were detected in 36% of patients either at baseline or during follow-up. Most immunized individuals had type I GT with complete absence of αIIbβ3 expression and carried biallelic null variants-particularly the ITGA2B c.1544+1G>A founder mutation prevalent in the French Gypsy (Manouche) population. Anti-αIIbβ3 antibody development occurred within 4 weeks after transfusion and was transient in most cases, disappearing within 18 months. Anti-HLA antibodies were found in approximately 25% to 30% of patients and tended to persist longer. Functional testing demonstrated that anti-αIIbβ3-positive sera significantly reduced fibrinogen binding but did not trigger CD62P exposure or complement-mediated platelet damage.
CONCLUSION: Antiplatelet immunization is common in GT, particularly among patients lacking αIIbβ3 expression. The findings highlight the influence of genotype on immunization risk and underscore the importance of prospective antibody monitoring.
OBJECTIVES: This study aimed to prospectively characterize the development and evolution of anti-αIIbβ3 and anti-HLA antibodies in a large cohort of French patients with GT and to assess their potential functional effects on platelet activity.
METHODS: This multicenter prospective study included 55 patients with GT who were followed up between 2018 and 2025. Anti-αIIbβ3 antibodies were detected using monoclonal antibody-specific immobilization of platelet antigen assays, and anti-HLA antibodies were screened using the Luminex-based technology. Functional analyses included fibrinogen binding, CD62P exposure, and complement deposition on donor platelets.
RESULTS: Anti-αIIbβ3 antibodies were detected in 36% of patients either at baseline or during follow-up. Most immunized individuals had type I GT with complete absence of αIIbβ3 expression and carried biallelic null variants-particularly the ITGA2B c.1544+1G>A founder mutation prevalent in the French Gypsy (Manouche) population. Anti-αIIbβ3 antibody development occurred within 4 weeks after transfusion and was transient in most cases, disappearing within 18 months. Anti-HLA antibodies were found in approximately 25% to 30% of patients and tended to persist longer. Functional testing demonstrated that anti-αIIbβ3-positive sera significantly reduced fibrinogen binding but did not trigger CD62P exposure or complement-mediated platelet damage.
CONCLUSION: Antiplatelet immunization is common in GT, particularly among patients lacking αIIbβ3 expression. The findings highlight the influence of genotype on immunization risk and underscore the importance of prospective antibody monitoring.
Предметные рубрики MeSH
HumansThrombastheniaProspective StudiesFemaleFrancePlatelet Glycoprotein GPIIb-IIIa ComplexMaleBlood PlateletsIntegrin alpha2AdultChildIntegrin beta3AdolescentHLA AntigensChild, PreschoolIsoantibodiesYoung AdultPlatelet TransfusionMutationMiddle AgedAutoantibodiesTime FactorsPhenotypeFibrinogenInfant