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T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein Ⅰ

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Cellular & Molecular Immunology 2019年第8期16卷 685-693页

作者： David Salem Rebecca Subang masataka kuwana Jerrold S.Levine Joyce Rauch Division of Rheumatology Department of MedicineResearch Institute of the McGill University Health CentreMontrealQCCanada Department of Allergy and Rheumatology Nippon Medical SchoolGraduate School of MedicineTokyoJapan Section of Nephrology Department of MedicineUniversity of Illinois at ChicagoChicagoILUSA Section of Nephrology Department of MedicineJesse Brown Veterans Affairs Medical CenterChicago IL USA

Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in *** to numerous molecularly distinct self-antigens emerge in a sequential manner over several years,leading to disease *** the earliest autoantibodies to appear are those targeting phospholipid-binding proteins,particularlyβ2-glycoprotein Ⅰ.Notably,mice immunized with β2-glycoprotein Ⅰ and lipopolysaccharide develop a strong T cell response to β2-glycoprotein Ⅰ that is associated with autoantibody production and renal disease,similar to that seen in human *** we hypothesized that mice with murine systemic lupus erythematosus,whether induced or spontaneous,should have T cells that recognizeβ2-glycoprotein *** evaluated the response of splenic T cells from mice with induced(C57BL/6 and C3H/HeN)and spontaneous(MRL/lpr)systemic lupus erythematosus to peptides spanning the entire sequence of humanβ*** found that mice with induced and spontaneous systemic lupus erythematosus recognize a common T cell epitope(peptide 31;LYRDTAVFECLPQHAMFG)in domain Ⅲ ofβ2-glycoprotein I.β2GPI-reactive CD4^(+)T cells from the two models differed primarily in cytokine production:T cells from mice with induced SLE expressed IFN-γ,while T cells from MRL/lpr mice expressed both IL-17 and IFN-γ,indicating that IL-17-expressing T cells are not necessary for generating aβ2GPI-reactive T cell *** data suggest that the generation of aβ2-glycoprotein Ireactive T cell response is shared by both induced and spontaneous models of systemic lupus erythematosus and that this T cell response may mediate epitope spread to autoantibodies in both models.

关键词： β2-glycoprotein I T cells systemic lupus erythematosus autoantibodies MHC class II haplotypes

Anti-Aminoacyl tRNA Synthetases Antibodies in Japanese Patients with Interstitial Lung Disease

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Open Journal of Rheumatology and Autoimmune Diseases 2018年第1期8卷 34-42页

作者： Shinji Sato Michito Hirakata Koichiro Asano masataka kuwana Division of Rheumatology Department of Internal Medicine Tokai University School of Medicine Isehara Japan Medical Education Center Keio University School of Medicine Tokyo Japan Division of Pulmonary Medicine Department of Internal Medicine Tokai University School of Medicine Isehara Japan Department of Allergy and Rheumatology Nippon Medical School Graduate School of Medicine Tokyo Japan

Objectives: In the present study, we have sought to establish the clinical and immunological characteristics of Japanese patients with interstitial lung disease (ILD). Methods: Serum samples from 35 patients of ILD were screened for autoantibodies using RNA and protein immunoprecipitation assays. Patients with or without serum antibodies to aminoacyl tRNA synthetases (ARS) were assessed clinically and compared. Results: Sera from 12 of 35 (34%) patients with ILD (mean age at onset = 49.7 yrs;range 27 - 65 yrs) were found to contain anti-ARS antibodies (anti-EJ: 3 patients;anti-OJ: 2 patients;anti-PL-12: 3 patients;anti-KS: 4 patients). Nine of the 12 (75%) were female. Six (50%) had Raynaud’s phenomenon, 5 (42%) had arthralgia/arthritis and four (33%) had rheumatoid factor. Lung biopsy specimens of 8 patients with anti-ARS antibodies were examined histologically in detail. The following was determined: Two patients had usual interstitial pneumonia;3 had non-specific interstitial pneumonia;one had organizing pneumonia;one had lymphocyte interstitial pneumonia and the remaining patient had desquamative interstitial pneumonia. Age at disease onset was significantly lower and the frequency of Raynaud’s phenomenon was significantly greater in these patients compared to anti-ARS-negative patients (49.7 yrs vs. 62.6 yrs, p = 0.004;50% vs. 4%, p = 0.003, respectively). Conclusions: These results indicate that the presence of anti-ARS autoantibodies correlates with ILD without definite diagnosis of connective tissue diseases as well as polymyositis/dermatomyositis (PM/DM) with ILD in Japanese patients.

关键词： Interstitial Lung Disease (ILD) Anti-Aminoacyl tRNA Synthetases (ARS) Antibodies Autoantibody Interstitial Pneumonia with Autoimmune Features (IPAF)

Clinical Phenotype of Japanese Patients with Dermatomyositis—Classification Based on Dermatomyositis-Specific Autoantibodies

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Open Journal of Rheumatology and Autoimmune Diseases 2014年第2期4卷 124-130页

作者： Shinji Sato masataka kuwana Michito Hirakata Shinichi Nogi Noriko Sasaki Naofumi Chinen Kiri Honda Eiko Saito Takayuki Wakabayashi Chiho Yamada Yasuo Suzuki Division of Rheumatology Department of Internal Medicine Keio University School of Medicine Tokyo Japan Division of Rheumatology Department of Internal Medicine Tokai University School of Medicine Isehara Japan

Objectives: To correlate the precise specificity of autoantibodies in Japanese dermatomyositis (DM) patients with their clinical phenotypes. Methods: Serum samples from 94 adult DM patients (67 with classical DM and 27 with clinically amyopathic dermatomyositis, CADM) were screened for autoantibodies using immunoprecipitation assays. Patients with antibodies against aminoacyl transfer RNA synthetase (ARS), Mi-2 or who had other autoantibodies were assessed for clinical symptoms and laboratory findings. Results: Sera from 27 of 94 DM patients (29%) were found to have anti-ARS antibodies. Nineteen (20%) had anti-CADM-140/MDA5, 5 (5%) had anti-Mi-2, and 8 (6%) had anti-p155/TIF1-γ. Anti-MJ/NXP-2 was not found in our series of adult DM. Seventeen patients with anti-ARS had fever and 22 had arthritis and interstitial lung disease (ILD), compatible with a diagnosis of anti-ARS syndrome. Seventeen of 19 (89%) with anti-CADM-140/MDA5 had ILD, 16 (84%) of whom developed rapidly progressive ILD (RP-ILD). Four of 5 (80%) with anti-Mi-2 had heliotrope rash and/or Gottron’s sign/papules, and 2 (40%) had V-sign and/or shawl-sign rash, whereas no ILD or malignancy was detected. As seen with anti-Mi-2-positive patients, a low frequency of ILD (13%) was found in patients with anti-p155/TIF1-γ but 6 of 8 (75%) had malignancy during their course. The frequency of ILD was significantly higher in patients with anti-ARS or anti-CADM-140/MDA5 compared with anti-Mi-2 or anti-p155/TIF1-γ (81% and 89%, respectively). It should be noted that anti-CADM-140/MDA5-positive patients suffered significantly more RP-ILD compared to patients with anti-ARS (84% vs. 7%, P < 0.0001). On the other hand, anti-p155/TIF1-γ positive patients had a significantly higher rate of malignancy compared with anti-ARS-, anti-CADM-140/MDA5-and anti-Mi-2-positive patients (75% vs. 7%: P = 0.0004, 5%: P = 0.0006, 0%: P = 0.02, respectively). Conclusions: These results indicate that in addition to antibodies previously id

关键词： Dermatomyositis (DM) Interstitial lung Disease (ILD) Rapidly Progressive Interstitial Lung Disease (RP-ILD) Malignancy Myositis-Specific Autoantibodies

皮肌炎／临床无肌病性皮肌炎患者血清中CADM-140抗体的检测和临床意义

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中华皮肤科杂志 2011年第7期44卷 461-464页

作者：曹华李霞亢延卿施若非周敏 masataka kuwana 丁晓毅郑捷上海交通大学医学院附属瑞金医院皮肤科 200025 上海交通大学医学院附属瑞金医院放射科 200025 上海交通大学医学院附属瑞金医院呼吸科 200025 日本东京庆音义塾大学医学部风湿病学科

目的对皮肌炎（DM）／临床无肌病性皮肌炎（CADM）患者进行CADM-140抗体检测，探讨CADM-140抗体与临床特征间的联系。方法采集38例DM（22例）／CADM（16例）患者血清，另外采集46例伴有肺间质病变的其他结缔组织病患者血清，包括8例多... 详细信息

目的对皮肌炎（DM）／临床无肌病性皮肌炎（CADM）患者进行CADM-140抗体检测，探讨CADM-140抗体与临床特征间的联系。方法采集38例DM（22例）／CADM（16例）患者血清，另外采集46例伴有肺间质病变的其他结缔组织病患者血清，包括8例多发性肌炎、15例系统性红斑狼疮、5例系统性硬化病、6例干燥综合征、6例混合性结缔组织病、6例特发性肺纤维化和5例正常对照者。以重组黑素瘤分化相关基因5（rMDA-5）为底物，通过ELISA检测患者血清中CADM-140抗体，比较CADM-140抗体阳性与阴性患者的临床特征。结果①16例CADM和22例DM患者血清CADM-140抗体阳性例数分别为7例和2例，CADM患者阳性率（43．8％）显著高于DM（9．1％）（P〈0．05），46例伴有肺问质病变的其他结缔组织病患者及5例正常人均阴性；②CADM-140抗体阳性患者皮肤溃疡和坏死的发生率为8／9，红细胞沉降率为（40．8±23．1）mm／1h，CADM-140抗体阴性组分别为6．9％和（22．5±16．8）mm／1h，两组比较，P〈0．01和〈0．05；CADM-140抗体阳性患者乳酸脱氢酶水平显著高于阴性组（分别为328．3±104．2和241．1±100．3IU／L，P〈0．05），而肌酸激酶显著低于阴性组（分别为156．3±260．8和1806．2±3737．1IU／L，P〈0．05）；两组问抗核抗体阳性率和恶性肿瘤发生率的差异无统计学意义；③CADM-140抗体阳性患者不仅肺间质病变发生率显著高于阴性组（分别为9／9和48．3％，P〈0．01），而且急进型肺间质病变发生率也显著高于阴性组（分别为5／9和0，P〈0．05）。阳性组肺高分辨率CT评分（122．9±54．8）显著高于阴性组（70．0-4-59．8）（P〈0．05）。结论通过检测CADM-140抗体不仅可以判断DM／CADM是否合并肺间质病变，还可能是伴发急进型肺问质病变的血清学标记，动态观察血清CADM-140抗体水平也许有助于预测肺间质病变病程。

关键词：皮肌炎肺疾病间质性临床无肌病性皮肌炎 CADM-140抗体

皮肌炎/临床无肌病性皮肌炎患者中CADM-140抗体的检测和临床意义

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皮肌炎/临床无肌病性皮肌炎患者中CADM-140抗体的检测和临床意义

抗MDA5抗体阳性的DM/CADM患者的肺HRCT影像学特点

2011全国中西医结合皮肤性病学术会议

作者：曹华李霞亢延卿施若非周敏 masataka kuwana 丁晓毅郑捷上海交通大学医学院附属瑞金医院皮肤科瑞金医院放射科瑞金医院呼吸科庆应义塾大学医学部风湿病学科

目的对38例皮肌炎/临床无肌病性皮肌炎(DM/CADM)患者进行CADM-140抗体检测,探讨CADM-140抗体与临床特征间的联系。方法以重组黑素瘤分化相关基因5(rMDA-5)为底物通过ELISA检测患者血清中CADM-140抗体,比较CADM-140抗体阳性与阴性患者的...

目的对38例皮肌炎/临床无肌病性皮肌炎(DM/CADM)患者进行CADM-140抗体检测,探讨CADM-140抗体与临床特征间的联系。方法以重组黑素瘤分化相关基因5(rMDA-5)为底物通过ELISA检测患者血清中CADM-140抗体,比较CADM-140抗体阳性与阴性患者的临床特征。结果①16例CADM和22例DM患者血清CADM-140抗体阳性例数分别为7例和2例,因此CADM患者CADM-140抗体阳性率显著高于DM(43.8%vs 9.1%,P<0.05)。CADM-140抗体不存在于伴有肺间质病变的多发性肌炎(PM)、系统性红斑狼疮(SLE)、干燥综合症(SS)、系统性硬皮病(SSc)和其他结缔组织病。②CADM-140抗体阳性患者皮肤溃疡和坏死的发生率和血沉(ESR)显著高于阴性组(88.9%vs6.9%,P<0.01,40.8±23.1 vs 22.5±16.8,P<0.05);CADM-140抗体阳性患者乳酸脱氢酶(LDH)显著高于阴性组(339.8±134.7 vs 193.4±53.0,P<0.01),而肌酸激酶(CK)显著低于阴性组(156.3±260.8vs 1806.2±3737.1,P<0.05);两组间抗核抗体(ANA)阳性率和恶性肿瘤发生率的差异无统计学意义。③CADM-140抗体阳性患者不仅肺间质病变发生率显著高于阴性组(100%vs 48.3%,P<0.05),而且急进型肺间质病变发生率也显著高于阴性组(55.6%vs 0,P<0.05)。阳性组肺HRCT评分显著高于阴性组(99.7±72.6 vs 32.1±44.3,P<0.01)。结论通过检测CADM-140抗体不仅可以判断DM/CADM是否合并肺间质病变,还可以作为伴发急进型肺间质病变的DM/CADM的血清学标记,动态观察血清CADM-140抗体水平有助于预测肺间质病变病程。

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抗MDA5抗体阳性的DM/CADM患者的肺HRCT影像学特点