The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura

HLA-DRB1*11 is a strong risk factor for acquired thrombotic thrombocytopenic purpura in children

“…1 Characterization of anti-ADAMTS13 autoantibodies showed that the immune response against ADAMTS13 is polyclonal and mostly targets the spacer domain of ADAMTS13 with predominant immunoglobulin G (IgG) 1 and IgG4 subclasses. [3][4][5][6] Pathophysiological mechanisms involved in the loss of tolerance of the immune system towards ADAMTS13 are still unknown.…”

“…7 A strong association between the HLA region, the generation of autoantibodies against self-antigen and autoimmune diseases has been described. 8 Four European independent groups identified HLA-DRB1*11 antigen as a strong risk factor for autoimmune TTP in Caucasian people 6,[9][10][11] suggesting that CD4+ T helper (Th) cells contribute to the pathogenesis of the disease, but this risk factor was not found in Black people. 12 HLA-DQB1*03 and HLA-DQB1*03:01 were also reported as a risk factor for autoimmune TTP.…”

“…13 Moreover, HLA-DRB1*04 was found underrepresented in acquired TTP patients, and is likely to protect against the development of the disease. 6,[9][10][11][12] Also, peptides derived from the CUB1 and CUB2 domains of ADAMTS13 are potential immunodominant T-cell epitopes in TTP patients.…”

“…14 All studies devoted to the investigation of the HLA system in acquired TTP were conducted exclusively in adult patients. 6,[9][10][11][12][13] For this study, we hypothesized that particular HLA alleles may be involved in the process leading to a loss of tolerance of the immune system against ADAMTS13 in child-onset acquired TTP patients and we focused on the allele frequencies of HLA-DRB1*11, -DRB1*04 and -DQB1*03.…”

“…We specifically considered these alleles as candidate risk factors for autoimmunity in acquired TTP. 6,[9][10][11][12][13] . The blood samples for HLA typing were analyzed for HLA-DRB1 and -DQB1 alleles as described previously.…”