HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to di ff erent HLA-DR

被引：22

作者：

Sakai, Kazuya ^{[1
]}

Kuwana, Masataka ^{[2
]}

Tanaka, Hidenori ^{[3
]}

Hosomichi, Kazuyoshi ^{[4
]}

Hasegawa, Atsushi

Uyama, Hiroki

Nishio, Kenji ^{[5
]}

Omae, Takashi ^{[6
]}

Hishizawa, Masakatsu ^{[7
]}

Matsui, Masashi ^{[8
]}

Iwato, Koji ^{[9
]}

Okamoto, Akinao ^{[10
]}

Okuhiro, Kazuki ^{[11
]}

Yamashita, Yukiko ^{[12
]}

Itoh, Masataka ^{[13
]}

Kumekawa, Hanae ^{[14
]}

Takezako, Naoki ^{[15
]}

Kawano, Noriaki ^{[16
]}

Matsukawa, Toshihiro ^{[17
]}

Sano, Haruna ^{[18
]}

Ohshiro, Kazuiku ^{[19
]}

Hayashi, Kunio ^{[20
]}

Ueda, Yasunori ^{[21
]}

Mushino, Toshiki ^{[22
]}

Ogawa, Yoshiyuki ^{[23
]}

Yamada, Yuji ^{[24
]}

Murata, Mitsuru ^{[25
]}

Matsumoto, Masanori ^{[1
]}

机构：

[1] Nara Med Univ, Dept Blood Transfus Med, Kashihara, Nara, Japan

[2] Nippon Med Sch, Dept Allergy & Rheumatol, Tokyo, Japan

[3] HLA Fdn Lab, Kyoto, Japan

[4] Kanazawa Univ, Grad Sch Med Sci, Dept Bioinformat & Genom, Kanazawa, Ishikawa, Japan

[5] Nara Med Univ, Dept Gen Internal Med, Kashihara, Nara, Japan

[6] Nara Med Univ, Dept Pediat, Kashihara, Nara, Japan

[7] Kyoto Univ, Dept Hematol & Oncol, Kyoto, Japan

[8] Kyoto City Hosp, Dept Hematol, Kyoto, Japan

[9] Hiroshima Red Cross Hosp, Dept Hematol, Hiroshima, Japan

[10] Fujita Hlth Univ, Dept Hematol, Toyoake, Aichi, Japan

[11] Oita Prefectural Hosp, Dept Hematol, Oita, Japan

[12] Ashiya Municipal Hosp, Dept Hematol & Oncol, Ashiya, Japan

[13] Tokyo Metropolitan Bokutoh Hosp, Dept Pediat, Tokyo, Japan

[14] Tokyo Teishin Hosp, Dept Hematol, Tokyo, Japan

[15] Natl Disaster Med Hosp, Dept Hematol, Tachikawa, Tokyo, Japan

[16] Miyazaki Prefectural Miyazaki Hosp, Dept Internal Med, Miyazaki, Japan

[17] Kushiro Rosai Hosp, Dept Internal Med, Kushiro, Japan

[18] Saga Ken Med Ctr Koseikan, Dept Hematol, Saga, Japan

[19] Okinawa Prefectural Nanbu Med Ctr & Child Med Ctr, Dept Hematol, Okinawa, Japan

[20] Meiwa Hosp, Dept Hematol, Nishinomiya, Hyogo, Japan

[21] Kurashiki Cent Hosp, Dept Hematol Oncol, Kurashiki, Okayama, Japan

[22] Wakayama Med Univ, Dept Hematol Oncol, Wakayama, Japan

[23] Gunma Univ, Grad Sch Med, Dept Hematol, Maebashi, Gunma, Japan

[24] Saitama Med Univ, Dept Gen Internal Med, Moroyamamachi, Japan

[25] Keio Univ, Sch Med, Dept Lab Med, Tokyo, Japan

来源：

BLOOD | 2020年 / 135卷 / 26期

关键词：

THROMBOTIC THROMBOCYTOPENIC PURPURA; FACTOR-CLEAVING PROTEASE; VACCINE DESIGN; T-CELLS; SUSCEPTIBILITY; IDENTIFICATION; SPECIFICITY; SUPERTYPES; COMPLEX;

D O I：

10.1182/blood.2020005395

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 5.076; and OR, 0.23, Pc 5.034, 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.

引用

页码：2413 / 2419

页数：7