Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR], 3.06; corrected P [Pc] = .005), DRB3/4/5*blank (OR, 2.3; Pc = .007), DQA1*01:03 (OR, 2.25; Pc = .006), and DQB1*06:01 (OR,: 2.41; Pc = .003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs 6.0%; Pc < .001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR, 0.23; Pc = .076; and OR, 0.23, Pc = .034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in the Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and white individuals. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, bound to the shared ADAMTS13 peptide in an in silico prediction model.

Chronic graft‐versus‐host disease (cGVHD) is the most important complication resulting in the death of bone marrow transplantation (BMT) survivors. It is also a relatively rare cause of inflammatory myopathy (IM). We report the case of a 46‐year‐old woman who developed severe cGVHD‐related IM after BMT for myelodysplastic syndrome. She presented with severe muscle pain and weakness with cGVHD‐related symptoms in other organs. Myopathological analysis showed moderate cell infiltration with remarkable necrotic and regenerative fibers. Sarcoplasm and capillaries expressed C5b9 and myxovirus resistance protein 1. Non‐necrotic fibers in perifascicular regions expressed MHC‐II. Steroid therapy did not sufficiently control cGVHD‐related IM, and the patient was concurrently treated with an immunosuppressant. Our findings show that IM is a key manifestation of cGVHD and that the expression of interferon‐inducible proteins in muscle pathology is useful for identifying cGVHD‐related IM.

Background Patients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased. Objective We investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET. Methods Seventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF‐related parameters. We calculated the VWFM index, defined as the ratio of intensities of a patient's molecular weight‐categorized VWFMs, and those of a healthy subject's, using densitometric analysis. VWF degradation product (DP) was measured via ELISA using a monoclonal antibody that specifically recognizes Y1605 at the C‐terminal boundary, which is exposed following ADAMTS13‐mediated cleavage of the Y1605‐M1606 bond of the VWF A2 domain. Results Patients with higher platelet counts had a significantly reduced high molecular weight (HMW)‐VWFM index and an increased VWF‐DP:VWF antigen (Ag) ratio compared to those with lower platelet counts. On multivariate analysis, the VWF‐DP/VWF:Ag ratio was an independent predictor of the HMW‐VWFM index. Patients who underwent cytoreductive therapy had a significantly higher HMW‐VWFM index and lower VWF‐DP/VWF:Ag ratio than those who did not. Among individual patients, there was also a significant increase in the HMW‐VWFM index and a decrease in the VWF‐DP/VWF:Ag ratio after cytoreductive therapy compared to pre‐therapy values. Conclusion In patients with ET, an increased platelet count is associated with enhanced cleavage of VWF at the Y1605‐M1606 bond, primarily by ADAMTS13, leading to AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWF cleavage, and improves VWFM distributions.

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