Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.

A man with non-small-cell lung cancer who was negative for anti-nuclear antibodies was admitted for dyspnea after immune checkpoint inhibitor (ICI) administration. Computed tomography (CT) showed complexed radiologic features, including subpleural and basal predominant reticular shadow with cystic structures and peribronchovascular consolidation. Although we treated him with high-dose steroid under a diagnosis of ICI-related pneumonitis, he developed acute exacerbation of pneumonitis with progressive fibrosis and volume loss. A re-evaluation identified anti-aminoacyl-tRNA synthetase antibody in the serum collected before ICI administration. This case highlights the importance of re-evaluating pre-existing autoimmune disorders in patients who develop ICI-related pneumonitis with atypical radiologic features.

A 59-year-old man who had smoked for 23 pack-years was admitted to our hospital because of two-month history of back pain. The chest computed tomography scan demonstrated combined pulmonary fibrosis and emphysema (CPFE) and an irregular shaped nodule in the left lower lobe of the lung. A biopsy obtained from samples from subcarinal lymph nodes revealed non-small cell lung cancer. Anti-aminoacyl-tRNA synthetase (ARS) antibody was elevated up to 166 U/mL, although he had no symptoms suggestive connective tissue diseases. It is well known that most of CPFE patients are current or former heavy smokers, and some researchers described the relationship between CPFE and connective tissue diseases. To our best knowledge, this was the first report of lung cancer in patient with anti-ARS antibody-positive CPFE. In some anti-ARS antibody-positive patients, smoking might have a relationship with development of CPFE and lung cancer.

Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of central and peripheral vascular disorders, including carotid, coronary and peripheral arterial diseases, and Raynaud\'s phenomenon. Recently, associations of plasma homocysteine levels with autoimmune diseases such as systemic lupus erythematodes and systemic sclerosis have been reported. However, no study analyzed the association between plasma homocysteine levels and dermatomyositis (DM). The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with DM. Plasma homocysteine levels in 28 Japanese patients with DM and 22 healthy controls were examined. We found that the plasma homocysteine levels in DM patients were significantly higher than those in healthy individuals (15.8 ± 1.1 vs 8.5 ± 0.5 µmol/L, P < 0.01). Presence of mechanic\'s hand, complication of interstitial lung disease (ILD), high serum Krebs von den Lungen-6 (KL-6), surfactant protein-D and creatine kinase levels, and anti-aminoacyl-tRNA synthetase (ARS) antibody (Ab) positivity were significantly more prevalent among DM patients with elevated plasma homocysteine levels. The plasma homocysteine levels in DM patients with mechanic\'s hand, ILD and anti-ARS Ab were significantly higher than those in DM without those features. Furthermore, the plasma homocysteine levels were positively correlated with serum KL-6 levels. These results suggest that the pathogenesis of elevated plasma homocysteine levels may be associated with ILD in DM patients, especially with anti-ARS Ab, and further examination is required.

A 55-year-old man who had been diagnosed with autoimmune pancreatitis five years earlier was referred to our department because of finger swelling, finger stiffness and the presence of interstitial lung disease (ILD). The patient was diagnosed with Sjögren\'s syndrome according to the pathological findings of minor salivary glands and positive anti-SS-A antibodies. Later, at age 58, he was hospitalised due to the exacerbation of the ILD. Serum IgG4 level was checked and was found to be elevated (417 mg/dL). After the introduction of cyclosporine in addition to the prednisolone, at age 60, the ILD disease activity stabilised. However, at age 62, fever, myalgia and mechanic\'s hands appeared. His serum creatine kinase level was high, and magnetic resonance imaging showed inflammatory findings of muscle. In-house ELISA clarified that his serum carried anti-PL-7 antibody among anti-aminoacyl-tRNA synthetase antibodies. This is a unique case who had overlapping features of IgG4-related autoimmune pancreatitis, Sjögren\'s syndrome and anti-synthetase syndrome. Although the aetiology of the complications in this patient is obscure, autoimmunity might have played a significant role in the disease conditions and prognosis of the present case with IgG4-related disease.

Objective: To provide reference for clinicians in diagnosis and treatment of antisynthetase syndrome with interstitial pulmonary disease (ASS-ILD) by analyzing the clinical features, imaging features and pulmonary function changes of ASS-ILD patients. Methods: A total of 92 patients with ASS-ILD diagnosed in the Respiratory Center of China-Japan Friendship Hospital from January 2015 to May 2018 were included, clinical manifestations, high-resolution computed tomography (HRCT), pulmonary function test, treatment and outcome were retrospectively analyzed. Results: The average age of the 92 patients was (58.6±12.2) years with a ratio of male to female 1∶1.79. The main types of anti-synthetase antibody were anti-Jo-1 antibody (37 cases, 40.2%) and anti EJ antibody (26 cases, 28.3%). The most common symptoms of ASS-ILD were cough (79 cases, 85.9%), shortness of breath (60 cases, 65.2%), expectoration (54 cases, 58.7%), fever (34 cases, 36.9%), and common signs were craftsman\'s hand (30 cases, 32.6%) and joint pain (23 cases, 25.0%). The most common imaging findings in HRCT were ground-glass opacities(68 cases, 73.9%), reticulations (45 cases, 48.9%), tractive bronchiectasis (40 cases, 43.5%) and consolidation (39 cases, 42.4%). The most common types of ILD were non-specific interstitial pneumonia (NSIP) (63 cases, 68.5%), followed by NSIP-organic pneumonia (OP) (12 cases, 13.0%). The main type of lung function impairment was mild restrictive ventilation dysfunction. There were no significant differences in clinical features, imaging findings and pulmonary function changes in different subtypes of ASS-ILD patients (all P>0.05). Corticosteroids was used in 78 (84.8%) of ASS-ILD patients, and 34 cases (37.0%) were given cyclophosphamide. A total of 91 patients (98.9%) were discharged with improvement and 1 anti-EJ positive patient died. Conclusions: ASS-ILD occurs frequently in middle-aged and old women. Respiratory symptoms, craftsman\'s hands and arthritis are the most common clinical manifestations. The most common imaging types of ILD are NSIP and NSIP-OP. Corticosteroids is commonly used for treatment.
目的： 总结抗合成酶综合征（ASS）合并间质性肺病（ILD）患者的临床特征。 方法： 回顾性分析2015年1月至2018年5月中日友好医院呼吸中心诊断为ASS-ILD患者92例，对其初诊时的临床表现、高分辨率CT（HRCT）影像学特点、肺功能指标以及治疗与转归进行总结分析。 结果： ASS-ILD患者年龄（58.6±12.2）岁（范围：17~83岁），男女比为1∶1.79，抗合成酶抗体分型以抗Jo-1抗体阳性（37例，40.2%）和抗EJ抗体阳性（26例，28.3%）为主。ASS-ILD最常见的症状是咳嗽（79例，85.9%）、气短（60例，65.2%）、咳痰（54例，58.7%）、发热（34例，36.9%），体征常见技工手（30例，32.6%）及关节疼痛（23例，25.0%）。CT影像学上以磨玻璃影（68例，73.9%）、网格影（45例，48.9%）、牵拉性支气管扩张（40例，43.5%）以及实变（39例，42.4%）常见，ILD类型以非特异性间质性肺炎（NSIP）（63例，68.5%）最多见，其次是NSIP-机化性肺炎（OP）（12例，13.0%）。肺功能改变主要为轻度限制性通气功能障碍。不同抗合成酶抗体亚型的ASS-ILD患者之间临床、影像学及肺功能比较差异均无统计学意义（P值均>0.05）。78例（84.8%）患者应用激素治疗，34例（37.0%）使用环磷酰胺。91例（98.9%）患者好转出院，1例抗EJ阳性患者因呼吸衰竭死亡。 结论： ASS-ILD以中老年女性多发，临床表现以呼吸道症状、技工手、关节炎常见，影像学最常见的类型为NSIP和NSIP-OP，临床治疗常应用激素。.

Patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies frequently experience complications of interstitial pneumonia (ARS-IP), and the computed tomography (CT) of ARS-IP frequently shows nonspecific interstitial pneumonia (NSIP) pattern. The CT pattern of ARS-IP might be different from that of idiopathic IP. However, the clinical differences in patients with ARS-IP and idiopathic IP showing the similar CT patterns have not yet been well studied. The objective of this study was to evaluate the clinical differences between patients with ARS-NSIP and idiopathic NSIP (I-NSIP).
Two groups of 34 patients each, with ARS-NSIP and I-NSIP, who visited Hiroshima University Hospital between January 2005 and December 2017, were enrolled. Clinical features and outcomes were retrospectively compared between the two groups.
The ARS-NSIP group included more female patients and significantly younger patients than the I-NSIP group. The percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) was significantly higher, and the CD4/CD8 ratio in BALF was significantly lower in the ARS-NSIP group compared with the I-NSIP group. The proportion of patients with traction bronchiectasis detected by CT was significantly higher in I-NSIP compared with ARS-NSIP. The number of patients who received corticosteroid and/or immunosuppressant therapy was significantly larger in the ARS-NSIP group than in the I-NSIP group. In addition, the patients in the I-NSIP group who underwent the immunosuppressive therapy demonstrated shorter survival than those who underwent no treatment; this tendency was not observed in the ARS-NSIP group. The 10-year survival rate of patients in the ARS-NSIP group was significantly higher than that of patients in the I-NSIP group (91.8% vs. 43.0%; log-rank, p = 0.012). The multivariate survival analysis revealed that positive anti-ARS antibody was an independent favorable prognostic factor in the patients with NSIP (OR, [95% CI]:0.12 [0.02-0.55], p = 0.013).
Patients with ARS-NSIP had a significantly better prognosis than those with I-NSIP; this may be associated with the sensitivity to immunosuppressive therapies, and the different findings of BALF and HRCT between the two groups.

Transbronchial lung cryobiopsy (TBLC) is a useful and safe method for the diagnosis of interstitial lung disease (ILD). Herein, we describe the cases of two patients who developed ILD from anti-aminoacyl-tRNA synthetase syndrome with respiratory failure. TBLC was performed instead of surgical lung biopsy. There were no complications, and sufficient specimens were harvested to make the precise histopathological diagnosis. TBLC should be considered as a critical approach for the histopathological diagnosis of ILD in patients who cannot undergo surgical lung biopsy because of respiratory failure.

Objective: To describe the clinical and radiological characteristics of antisynthetase syndrome associated interstitial lung disease in patients with different serum anti-aminoacyl-tRNA synthetase antibodies. Methods: We conducted a retrospective analysis of 5 adult patients with antisynthetase syndrome associated interstitial lung disease in Peking Union Medical College Hospital. Their clinical and chest radiological data were analyzed and relevant literatures were reviewed. Results: Among these 5 patients, there were 1 male and 4 females, aged from 32 y to 67 y, with a mean age of 53 y. Cough and exertional dyspnea were the main clinical complaints. Four cases showed mechanic\'s-like hands, and all of the 5 cases had Velcro rales in the basal lungs. None of them showed clubbing. Creatine kinase was elevated in 1 case with anti-Jo-1 synthetase antibody, and anti-nuclear antibody was positive in 4 cases, with different titers from 1∶80 to 1∶320, and anti-Ro-52 antibody was positive in 3 cases. Anti-aminoacyl-tRNA synthetase antibody spectrum analysis showed 1 case with anti-Jo-1, 1 anti-PL-7, 1 anti PL-12, 1 anti-EJ and 1 anti-OJ synthetase antibody, respectively. Chest high resolution CT showed nonspecific interstitial pneumonia pattern in 1 case, and nonspecific interstitial pneumonia pattern with organizing pneumonia pattern in 4 cases. All the cases responded to immunosuppressive therapy including corticosteroids (with starting prednisone dosage more than 1 mg·kg(-1)·d(-1)) plus azathioprine or Mycophenolate mofetil. Conclusions: Antisynthetase syndrome associated interstitial lung disease, characterized by the presence of different anti-tRNA synthetase antibodies, is an increasingly recognized clinical entity. Clinical and radiological features of different subtypes of antisynthetase syndrome are relatively heterogeneous. Nonspecific interstitial pneumonia pattern, nonspecific interstitial pneumonia pattern with organizing pneumonia pattern and organizing pneumonia pattern were common chest HRCT patterns. Prednisone plus immunosuppressive agents are the recommended first line therapy.
目的： 分析常见的不同亚型的抗合成酶综合征相关性间质性肺疾病的临床及影像学表现。 方法： 回顾北京协和医院呼吸内科2015年3月至2017年3月住院的5例不同临床亚型的抗合成酶综合征相关性间质性肺疾病患者，其中男1例、女4例，年龄32～67岁，平均年龄53岁。分析其临床及胸部高分辨率CT的主要特点。 结果： 5例患者均表现为咳嗽、活动后气短，均存在明确的双下肺为主的爆裂音，4例存在\"技工手\" ，均无\"杵状指\" 。1例血清肌酸激酶升高，4例抗核抗体阳性(1∶80～1∶640)，3例RO-52阳性；肌炎抗体谱抗Jo-1、抗PL-7、抗PL-12、抗EJ及抗OJ阳性各1例。1例胸部高分辨率CT表现符合非特异性间质性肺炎，4例表现为非特异性间质性肺炎合并机化性肺炎。所有患者接受起始剂量为≥1 mg·kg(－1)·d(－1)泼尼松联合免疫抑制剂治疗，其中2例使用硫唑嘌呤，3例使用吗替麦考酚酯，所有患者治疗后临床症状和胸部CT表现均明显改善。 结论： 抗合成酶综合征相关性间质性肺疾病逐渐被临床认识，不同亚型的抗合成酶综合征的临床表现和胸部影像学表现可能存在差异，以非特异性间质性肺疾病、非特异性间质性肺炎合并机化性肺炎或机化性肺炎多见，治疗推荐使用糖皮质激素联合免疫抑制剂作为初始治疗。.