Abstract Number: OC 04.5
Meeting: ISTH 2022 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » ADAMTS13 and TTP
Background: Despite significant advances in immune Thrombotic Thrombocytopenic Purpura (iTTP) care relapses occur in 30-50% of patients. This causes significant morbidity and mortality, and the aetiology remains poorly understood.
Aims: We undertook HLA and genome-wide analysis to identify genetic associations for iTTP relapse.
Methods: 155 iTTP patients (44 relapsed, 111 non-relapsed) of European genetic ancestry were genotyped at 3,649,347 Single Nucleotide Polymorphisms genome-wide. HLA imputation was performed using SNP2HLA (V1.0.3, European reference panel). Relapse data from the UK TTP registry (defined as ADAMTS13 relapse or clinical relapse) were used to identify iTTP relapse associations.
Results: Among 25 Class-II HLA types tested, HLA-DRB1*15:01 was identified as being associated with iTTP disease relapse (P=0.0008, see Table 1). HLA-DQB1*06:02 and HLA-DQA1*01:02, which are in linkage disequilibrium with HLA-DRB1*15:01, also showed evidence of association.
HLA-DRB1*11:01 and HLA-DQA1*03:01 (associated with risk of iTTP) were not associated with disease relapse (P=0.97 and 0.94 respectively). Genome-wide association analysis revealed that no genetic markers outside HLA region were significantly associated with iTTP relapse.
Conclusion(s): Here we demonstrate HLA-DRB1*15:01 being associated with iTTP relapse for the first time, but not HLA-DRB1*11:01. HLA-DRB1*11:01 is well established in iTTP risk, with functional studies demonstrating that this allele is associated with ADAMTS13 presentation in addition to autoreactive CD4+ Th-cells. HLA-DRB1*15:01 is associated with several other autoimmune conditions (notably multiple sclerosis and SLE). Subsequent functional studies in MS implicate HLA-DRB1*15:01 in autoreactive T-cell activity and antigen presentation, and it is possible that similar mechanisms are also important in iTTP relapse. This work has identified HLA-DRB1*15:01 as a means to potentially individualise monitoring to reduce relapse risk, in addition to increasing understanding of the pathophysiology in iTTP relapse.
To cite this abstract in AMA style:
Stubbs M, Doyle A, Cheshire C, Levine A, Thomas M, Westwood J, Kleta R, Gale D, Stanescu H, Scully M. Immune Medicated Thrombotic Thrombocytopenic Purpura relapse is associated with HLA-DRB1*15:01 [abstract]. https://abstracts.isth.org/abstract/immune-medicated-thrombotic-thrombocytopenic-purpura-relapse-is-associated-with-hla-drb11501/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/immune-medicated-thrombotic-thrombocytopenic-purpura-relapse-is-associated-with-hla-drb11501/