Using our diagnostic criteria, we could recruit relatively many patients with similar characteristics to those of idiopathic PPFE patients in the literature. The possibility of clinical diagnosis of idiopathic PPFE should be further discussed.

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Background and objective The efficacy of combination therapy with corticosteroids and CNI, TAC and CsA, for PM/DM‐ILD has been described retrospectively. However, it remains unknown which CNI treatment regimens, TAC or CsA regimens, are more effective as initial treatments for patients with PM/DM‐ILD. Methods We conducted a prospective multicentre, open‐label, randomized, 52‐week phase 2 trial. Patients with PM/DM‐ILD were randomly allocated to receive PSL plus TAC (TAC group) or PSL plus CsA (CsA group). The primary endpoint was PFS rate in the intention‐to‐treat population at 52 weeks. The secondary endpoints were OS rate at 52 weeks, changes in pulmonary function tests from baseline to 52 weeks and AE. Results Fifty‐eight patients were randomly assigned to the TAC group (n = 30) and the CsA group (n = 28). The PFS rates at 52 weeks were 87% in the TAC group and 71% in the CsA group (P = 0.16). The OS rates at 52 weeks were 97% in the TAC group and 93% in the CsA group (P = 0.50). The %FVC at 52 weeks in the per‐protocol populations significantly increased in both groups. None of the patients discontinued the treatment due to AE. Conclusion PSL plus TAC treatment may achieve a better short‐term PFS rate compared with PSL plus CsA treatment. Further studies must be conducted to evaluate the long‐term efficacy and safety of such treatment.

Pulmonary alveolar proteinosis (PAP) is a devastating lung disease caused by abnormal surfactant homeostasis, with a prevalence of 6–7 cases per million population worldwide. While mutations causing hereditary PAP have been reported, the genetic basis contributing to autoimmune PAP (aPAP) has not been thoroughly investigated. Here, we conducted a genome-wide association study of aPAP in 198 patients and 395 control participants of Japanese ancestry. The common genetic variant, rs138024423 at 6p21, in the major-histocompatibility-complex (MHC) region was significantly associated with disease risk (Odds ratio [OR] = 5.2; P = 2.4 × 10−12). HLA fine-mapping revealed that the common HLA class II allele, HLA-DRB1*08:03, strongly drove this signal (OR = 4.8; P = 4.8 × 10−12), followed by an additional independent risk allele at HLA-DPβ1 amino acid position 8 (OR = 0.28; P = 3.4 × 10−7). HLA-DRB1*08:03 was also associated with an increased level of anti-GM-CSF antibody, a key driver of the disease (β = 0.32; P = 0.035). Our study demonstrated a heritable component of aPAP, suggesting an underlying genetic predisposition toward an abnormal antibody production.

Objective. The efficacy of combination therapy with corticosteroid and calcineurin inhibitor [tacrolims (TAC) or cyclosporin A (CsA)] for polymyositis (PM)/dermatomyositis (DM)-associated interstitial lung diseases (PM/DM-ILD) has been described retrospectively. However, therapeutic effects of TAC regimen and CsA regimen have never been compared in randomized clinical trials. The aim of this prospective study was to compare the efficacy between prednisolone (PSL) plus TAC treatment and PSL puls CsA treatment in patients with PM/DM-ILD. Methods. We conducted multicenter, openlabel, randomized, 52-week phase 2 trial in patients with PM/DM-ILD. The patients were randomly allocated to receive PSL plus TAC treatment (TAC group) or PSL plus CsA treatment (CsA group). All patients received PSL orally (initial dose of 0.6 -1 mg/kg/day followed by slowly tapering). Intravenous methylprednisolone pulse therapy (1 g/day for 3 days) was permitted prior to oral PSL according to the disease activity. TAC or CsA was administered orally twice daily with adjusted for whole-blood trough level (TAC: 5 -10 ng/ml, CsA: 100 -150 ng/ml). The primary endpoint was progression-free survival (PFS) rate in the intention-to-treat population at week 52. We used a randomized phase 2 screening design with a two-sided α of 0.20 (wherein p < 0.20 designates a positive trial). Key secondary outcome was overall survival (OS) rate in the intention-to-treat population at week 52. Changes in pulmonary function tests from baseline to week 52 were evaluated in per protocol populations. This study is registered with UMIN Clinial Trials Registry (UMIN-CTR) system (https://www.umin.ac.jp/ctr/UMIN000015469). Results. Fifty-eight patients were randomly assigned to either TAC group (n = 30) or CsA group (n = 28). The PFS rates at 52-week were 86.7% in TAC group and 71.4% in CsA group (p = 0.16). The OS rates at 52-week were 96.7% in TAC group and 92.9% in CsA group (p = 0.50). %FVC at 52 week in the per protocol populations was significantly increased in the both groups. No differences were observed in the changes of

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