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Recent advances in the management and understanding of immunoglobulin (Ig)G4-related kidney disease (RKD) have emphasized the importance of urgent treatment in IgG4-related tubulointerstitial nephritis. On the other hand, to avoid long-term glucocorticoid toxicity, strategies for early withdrawal of steroids or combination of immunosuppressants, such as rituximab, and the minimum dose of steroids have been pursued. However, disease recurrence after reducing or stopping steroid therapy hampers early withdrawal of glucocorticoid maintenance therapy. In addition, knowledge has accumulated in diagnostic approaches including differential diagnosis of anti-neutrophil cytoplasmic antibodies-associated vasculitis, idiopathic multicentric Castleman’s disease, and Rosai–Dorfman disease with kidney lesion, which leads to earlier and precise diagnosis of IgG4-RKD. This review summarizes recent progress in the differential diagnosis of IgG4-RKD and related treatment strategies and recent topics of hypocomplementaemia, membranous glomerulonephritis, and IgG4-related pyelitis and periureteral lesion.

大阪府下から記録されている哺乳類、鳥類、両生類、爬虫類、魚類、昆虫類、その他無脊椎動物、コケ類、維管束植物について、主に明治時代以降に持ち込まれたと考えられる外来種を整理し目録を作成した。結果として哺乳類11種、鳥類12種、爬虫類3種、両生類2種、魚類45種、昆虫類・クモ類196種、その他無脊椎動物68種、コケ類3種、維管束植物種800種がリストアップされた。 This list shows non-native species that are thought to have been introduced mainly after the Meiji era and were recorded in Osaka Prefecture. As a result, the following species were listed, Mammals: 11 species, birds: 12 species, reptiles: 3 species, amphibians: 2 species, fish: 45 species, insects and spiders: 196 species, other invertebrates: 68 species, mosses: 3 species, vascular plant species: 800 species.

Background/Aim: The association between tumor PD-L1 expression and the rate of acquisition of the T790M mutation during treatment with first-/second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a matter of study. This retrospective study was conducted to evaluate the association of tumor PD-L1 expression with the time on treatment under EGFR-TKIs in patients with EGFR-mutant non-small cell lung cancer (NSCLC), treated with first-/second-generation EGFR-TKIs. Patients and Methods: We conducted a retrospective review of the medical charts of patients with EGFR-mutant NSCLC treated with first- /second-generation EGFR-TKIs. Time on treatment with EGFR-TKIs was defined as the sum of progression-free survival period (PFS) from the start of treatment with first- /second-generation EGFR-TKIs and the PFS from the start of osimertinib treatment after acquisition of the T790M mutation. Tumor PD-L1 expression was evaluated using the 22C3 antibody. Results: Data of a total of 49 patients were analyzed, including 20 patients with negative tumor PD-L1 expression (tumor proportion score 1%) and 29 patients with positive tumor PD-L1 expression (tumor proportion score ≥1%). In the negative tumor PD-L1 expression group, the T790M mutation was detected in 12 (75%) of the 16 patients. In the positive tumor PD-L1 expression group, the T790M mutation was detected 6 (31.6%) out of the 19 patients in whom it was tested. The median (95% confidence interval) time on treatment with EGFR-TKIs was 21.7 (12.9-24.8) months and 12.3 (5.6-22.2) months in the negative and positive tumor PD-L1 expression groups, respectively. Analysis using a Cox proportional hazards model identified performance status and presence/absence of tumor PD-L1 expression as significantly associated with the time on treatment with EGFR-TKIs. Conclusion: EGFR-mutant NSCLC patients with negative tumor PD-L1 expression showed a higher rate of acquisition of the T790M mutation and implementation rate of osimertinib therapy, leading to a longer time on treatment with EGFR-TKI.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.

Aim We report, herein, three cases of pleomorphic carcinoma of the lung treated with immune checkpoint inhibitors. Case 1: A 73-year-old man was diagnosed as having pleomorphic carcinoma of the lung and treated with pembrolizumab alone. However, he showed no response and died 4 months after the initiation of the treatment. Case 2: A 66-year-old man was diagnosed as having pleomorphic carcinoma of the lung. He was started on a combination regimen of pembrolizumab plus carboplatin plus nab-paclitaxel, and a remarkable response was observed. Case 3: A 49-year-old man was diagnosed as having pleomorphic carcinoma of the lung. He was started on pembrolizumab monotherapy as second-line treatment. Eleven months after the treatment initiation, computed tomography revealed the decrease of tumor diameter. Conclusion Immune checkpoint inhibitor therapy is expected to improve the prognosis of patients with pleomorphic carcinoma of the lung.

Purpose: We analysed the relationship between a history of immune checkpoint inhibitor (ICI) and overall survival in elderly patients with non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of the data of patients with NSCLC aged ≥70-year-old who had received systemic anticancer therapy between 2015 and 2019. Results: The analysis included the data of a total of 63 patients. Multivariate analysis revealed a significant association between a history of treatment with ICI and the overall survival. A significant interaction was also observed between a history of treatment with an ICI and the tumor histology. Conclusion: A significant association between history of ICI therapy and the overall survival was detected in elderly NSCLC patients aged ≥70-year-old in a clinical practice setting. Our results also suggested that the impact of ICI therapy on the survival differed depending on the tumor histology.

Objective The aim of the present study was to analyze the relationship between the patient characteristics and the timing of provision of an explanation about "Do Not Attempt Resuscitation (DNAR)" by attending physicians to advanced lung cancer patients. Methods We conducted a retrospective analysis of patients with advanced or postoperative recurrent lung cancer in whom systemic therapy was initiated between 2015 and 2016. Results The data of a total of 74 patients with lung cancer, including 59 patients with non-small cell lung cancer and 15 with small cell lung cancer were analyzed. The median overall survival of the patients was 10.0 months. Records of the explanation about DNAR by the physicians were available for 57 of the 74 (77.0%) patients. For 48 (64.9%) patients, the explanation was provided after the discontinuation of anticancer treatment, and for 9 (12.2%) patients, it was provided during the course of anticancer treatment. The provision of an explanation about DNAR during the course of treatment was associated with a poor performance status at the start of treatment (p=0.028), the tumor histology (p=0.037), the presence of driver gene mutation in the tumor (p=0.029), and shorter survival after the discontinuation of anticancer treatment (p

This study investigated the clinical features of IgG4-RKD patients with hypocomplementemia compared with those without it, so as to clarify the factors related to hypocomplementemia.In this single-center retrospective study, we analyzed the clinical features of 25 patients with IgG4-RKD according to the presence/absence of hypocomplementemia. Additionally, we validated the results of a single-center study in a separate large multicenter cohort of 328 patients with IgG4-RD, and searched for factors related to hypocomplementemia.Serum IgG levels (The present study suggests that hypocomplementemia is associated with elevation of IgG subclasses other than IgG4 including IgG1 in IgG4-RKD.

Background: Small cell lung cancer (SCLC) is a very aggressive cancer and recurrence is inevitable. Treatment of recurrent disease is important for improving the prognosis of patients with SCLC. Methods: We conducted a retrospective observational study to investigate the efficacy and safety of irinotecan monotherapy as third- or further-line treatment in patients with SCLC. Results: Data of 15 patients who had received irinotecan monotherapy as third- or further-line treatment between 2004 and 2019 were analyzed. The median progression-free survival duration (95% confidence interval) from the initiation of treatment with irinotecan was 2.7 (1.4–3.8) months, and the median overall survival duration (95% confidence interval) from the initiation of irinotecan treatment was 10.0 (3.9–12.9) months. Partial response, stable disease or non–complete response/non–progressive disease, and progressive disease were observed in 1, 6, and 8 patients, respectively. Adverse events ⩾ grade 3 in severity were observed in 2/2 (100%) patients who were homozygous for UGT1A1 mutation, 2/3 (66.7%) patients who were heterozygous for UGT1A1 mutation, 4/6 (66.7%) patients who had wild-type UGT1A1, and 2/4 (50.0%) patients in whom the UGT1A1 mutation status was unknown. Conclusion: Our results suggest that irinotecan monotherapy can be a useful alternative treatment option in the third-line setting for patients with SCLC.

Purpose We conducted a retrospective analysis of the data of patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to investigate the associations between clinical factors and the overall survival. Methods We retrieved the patient data from the medical charts. Patients who were diagnosed as having EGFR-mutant NSCLC and treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) between 2007 and 2020 at our institution were included in the analysis. Results A total of 130 patients were included in the analysis. A log-rank test identified EGFR exon 19 deletion in the tumor, an Eastern Cooperative Oncology Group performance status of 0–1, serum lactate dehydrogenase level, local therapy for brain metastasis, and sequential osimertinib therapy for patients with the T790M mutation acquired after primary EGFR-TKI therapy as being significantly associated with a better overall survival. Analysis using a Cox proportional hazards model identified EGFR exon 19 deletion in the tumor, an Eastern Cooperative Oncology Group performance status of 0–1, serum lactate dehydrogenase level, local therapy for brain metastasis, and sequential therapy with osimertinib as being independently associated with a prolonged overall survival. Conclusion Our analysis suggested that EGFR mutation status, an Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase level, local therapy for brain metastasis, and sequential therapy with osimertinib were associated with overall survival in patients with EGFR-mutant NSCLC in clinical practice settings.

Summary Background IgG4-related disease is a newly recognised immunopathological entity that includes autoimmune pancreatitis, IgG4-related sialadenitis, and IgG4-related kidney disease. To understand the genetic landscape of IgG4-related disease, we did a genome-wide association study. Methods We did a genome-wide association study of Japanese individuals, initially screening 857 patients with IgG4-related disease at 50 Japanese research institutions and DNA samples from 2082 healthy control participants from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience. From Oct 27, 2008, to July 22, 2014, we enrolled 835 patients and used data from 1789 healthy participants. Only patients with confirmed diagnosis of IgG4-related disease according to the international diagnostic criteria were included. Genotyping was done with the Infinium HumanOmni5Exome, HumanOmni2.5Exome, or HumanOmni2.5 Illumina arrays, and genomic distributions were compared between case and control samples for 958 440 single nucleotide polymorphisms. The HLA region was extensively analysed using imputation of HLA alleles and aminoacid residues. Fine mapping of the FCGR2B region was also done. Associations between clinical manifestations of disease and the genetic variations identified in these two genes were examined. Findings We identified the HLA-DRB1 (p=1·1×10−11) and FCGR2B (p=2·0×10−8) regions as susceptibility loci for IgG4-related disease. We also identified crucial aminoacid residues in the β domain of the peptide-binding groove of HLA-DRB1, in which the seventh aminoacid residue showed the strongest association signal with IgG4-related disease (p=1·7×10−14), as has been reported with other autoimmune diseases. rs1340976 in FCGR2B showed an association with increased FCGR2B expression (p=2·7×10−10) and was in weak linkage disequilibrium with rs1050501, a missense variant of FCGR2B previously associated with systemic lupus erythematosus. Furthermore, rs1340976 was associated with the number of swollen organs at diagnosis (p=0·011) and IgG4 concentration at diagnosis (p=0·035). Interpretation Two susceptibility loci for IgG4-related disease were identified. Both FCGR2B and HLA loci might have important roles in IgG4-related disease development. Common molecular mechanisms might underlie IgG4-related disease and other immune-related disorders Funding The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, and Kyoto University Grant for Top Global University Japan Project.

IgG4-related diseases (IgG4-RDs), such as autoimmune pancreatitis and IgG4-related Mikulicz disease, are often accompanied by intrathoracic lesions, which are called IgG4-related respiratory disease (IgG4-RRD). IgG4-RRD has few subjective symptoms, and is usually detected during workup of patients with extra-thoracic lesions of IgG4-RD. IgG4-RRD is characterized by various conditions, including masses, nodules, thickening, and infiltration at numerous sites in the thorax through lymphatic routes. Although elevated serum IgG4 concentrations and pathologic evidence of lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells are characteristic findings of IgG4-RD, other intrathoracic diseases, such as multicentric Castleman disease and malignancy, may present with similar findings. Developing diagnostic criteria for IgG4-RRD, including clinicoradiological and pathological characteristics, is necessary for its appropriate diagnosis.

Background/Aim: We conducted a retrospective analysis of the survival durations of 25 patients diagnosed as having non-squamous cell non-small cell lung cancer with negative or low tumor programmed death-ligand 1 (PD-L1) expression treated with immune checkpoint inhibitor (ICI) monotherapy. Patients and Methods: The progression-free (PFS) and overall (OS) survival were calculated from the initiation of ICI monotherapy. The association between the patient characteristics and the PFS was analyzed using Cox proportional hazards model. Results: The median PFS was 2.6 months, and the 12-month PFS rate was 9.3%. The median OS was 5.5 months, and the 12-month OS rate was 39.8%. A Cox proportional hazards model identified the neutrophil/lymphocyte ratio and presence of liver metastasis as being significantly associated with PFS. Conclusion: Our findings suggest that a subset of patients with non-squamous cell non-small cell lung cancer who show negative or low tumor PD-L1 expression could benefit from ICI monotherapy.

Rationale Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by an elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. Pathological changes are most frequently seen in the pancreas, lacrimal glands, and salivary glands, but pathological changes in the lung also exist. Linker for activation of T cell (LAT)Y136F knock-in mice show Th2-dominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. We have reported that LATY136F knock-in mice display several characteristic features of IgG4-RD and concluded that they constitute an appropriate model of human IgG4-RD in salivary glands, pancreas, and kidney lesions. Objectives The aim of this study is to evaluate whether lung lesions in LATY136F knock-in mice can be a model of IgG4-related lung disease. Methods Lung tissue samples from LATY136F knock-in mice (LAT) and wild-type mice (WT) were immunostained for IgG1 and obtained for pathological evaluation, and cell fractions and cytokine levels in broncho-alveolar lavage fluid (BALF) were analyzed. Results In the LAT group, IgG1-positive inflammatory cells increased starting at 4 weeks of age and peaked at 10 weeks of age. The total cell count and percentage of lymphocytes increased significantly in BALF in the LAT group compared to the WT group. In BALF, Th2-dominant cytokines and transforming growth factor-β were also increased. In the LAT group, marked inflammation around broncho-vascular bundles peaked at 10 weeks of age. After 10 weeks, fibrosis around broncho-vascular bundles and bronchiectasis were observed in LATY136F knock-in mice but not WT mice. Conclusions LATY136F knock-in mice constitute an appropriate model of lung lesions in IgG4-RD.

Immunoglobulin G4-related disease is a systemic disease characterised by tumefactive lesions with abundant IgG4-positive plasma cells and elevated serum IgG4 concentrations [1–4]. We previously assessed IgG4-related respiratory disease (IgG4-RRD) with extrathoracic manifestations [5]. IgG4-RRD develops through the lymphatic routes in the lungs and responds well to corticosteroid therapy with a benign prognosis [5–7]. However, whether interstitial pneumonia (IP) with IgG4-positive plasma cell infiltration in the lungs without the extrathoracic lesions of IgG4-related disease could be considered a type of IgG4-RRD is controversial., This study suggests that IgG4+ IP with abundant IgG4+ cells and elevated serum IgG4 levels could be treated differently from IgG4-related respiratory disease due to potential differences in disease behaviour and response to corticosteroid therapy https://bit.ly/3dUo2cu

Purpose: We analyzed the relationship between a history of immune checkpoint inhibitor and overall survival in patients with non-small cell lung cancer (NSCLC) aged ≥ 70 years. Methods: We conducted a retrospective analysis of the data of patients with NSCLC aged ≥70 years old who had received systemic anticancer therapy at our institution between 2015 and 2019. Results: The analysis included the data of a total of 63 patients, including 36 patients who had received immune checkpoint inhibitor therapy and 27 patients who had not received treatment with an immune checkpoint inhibitor. Univariate analysis revealed a longer overall survival in patients who had received treatment with an immune checkpoint inhibitor as compared to those who had not received treatment with an immune checkpoint inhibitor (median: 17.2 vs. 9.8 months; p = 0.026, log-rank test). Multivariate analysis revealed a significant association between a history of treatment with immune checkpoint inhibitors and the overall survival (hazard ratio, 95% confidence interval: 0.42, 0.20-0.86; p = 0.019, Cox proportional hazards model). A significant interaction was also observed between a history of treatment with an immune checkpoint inhibitor and the tumor histology (p = 0.006), the association between the overall survival and a history of immune checkpoint inhibitor therapy being stronger in the non-small cell lung cancer patients with squamous cell carcinoma than in those with adenocarcinoma. Conclusion: A significant association between history of immune checkpoint inhibitor therapy and the overall survival was detected in elderly NSCLC patients aged ≥70 years old in a clinical practice setting. Our results also suggested that the impact of immune checkpoint inhibitor therapy on the survival differed depending on the tumor histology.

The laomediid mud shrimp genus Axianassa Schmitt, 1924 is currently represented by 12 species worldwide. In this study, a new species of the genus, A. microlepis, is described and illustrated on the basis of two female specimens obtained from Awaji Island, eastern part of the Seto Inland Sea, Japan, at depth of 8 m. The type specimens were collected by means of an airlift suction sampler, which enables collection of infauna in subtidal soft sediments. The new species, representing the fourth species of the genus known from the western Pacific, is readily distinguished from other congeners by the unique structure of the antennal scaphocerite (short, non-dagger shaped, terminally rounded or having spine and blade), faintly crenulate rostral margins and the presence of a small lateral notch on the uropodal endopod. An amended identification key to the species of Axianassa and Heteroaxianassa Sakai, 2016 is provided.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic, multiorgan disease of unknown etiology. We aimed to classify IgG4-RD by a combination pattern of affected organs and identify the clinical features, including the comorbidities of each subgroup.Patients diagnosed with IgG4-RD between April 1996 and June 2018 were enrolled from three institutes. Hierarchical cluster analysis was performed using six frequently affected organs (lacrimal gland and/or orbit, salivary gland, lung, pancreas, kidney, and retroperitone and/or aorta). Clinical features, such as comorbidities and outcomes, were compared between clusters.In total, 108 patients enrolled in this cohort could be stratified into five distinct subgroups: group 1, lung dominant group; group 2, retroperitoneal fibrosis and/or aortitis dominant group; group 3, salivary glands limited group; group 4, Mikulicz's disease dominant group; and group 5, autoimmune pancreatitis with systemic involvement group. There were significant between-group differences in sex (male dominant in group 1, 2, and 5), history of asthma and allergies on the respiratory tract (most frequent in group 5), and malignancy (most frequent in group 5).IgG4-RD can be classified into subgroups according to the pattern of affected organs. Group 5 may have frequent complications with allergies and malignancies.

Background/aim Little information is available about the association between peripheral T-lymphocyte expression of programmed cell death protein 1 (PD1) and the efficacy of immune checkpoint inhibitor therapy in patients with non-small cell lung cancer (NSCLC). We analyzed the PD1 and cytotoxic T-lymphocyte associated protein 4 (CTLA4) expression in peripheral blood T-lymphocytes of patients with NSCLC receiving immune checkpoint inhibitor therapy. Patients and methods Patients with NSCLC who were scheduled to receive treatment with immune checkpoint inhibitors were prospectively enrolled in this study between November 2017 and November 2018. Peripheral blood samples were obtained within 1 week before or after the initiation of treatment with an immune checkpoint inhibitor. Results Flow cytometry was conducted in 19 patients. Patients were treated with nivolumab, pembrolizumab, or atezolizumab. The group with a high percentage of PD1+CD4+ T-lymphocytes relative to the total CD4+ T-lymphocyte count had a longer progression-free survival [median=6.0 (95% confidence intervaI=0.5-not estimated) months] than the group with a low percentage of PD1+CD4+ T-lymphocytes [median=1.1 (95% confidence intervaI=0.4-5.0) months; p=0.034, log-rank test]. However, no significant associations were detected with the percentages of CTLA4+CD4+, PD1+CD8+ or CTLA4+CD8+ T-lymphocytes in the peripheral blood. Conclusion A high percentage of peripheral CD4+PD1+ T-lymphocytes was associated with a longer progression-free survival in patients receiving treatment with an immune checkpoint inhibitor. The systemic immune system may have an influence on the efficacy of immune checkpoint inhibitor therapy in patients with NSCLC.

Background The aim was to further characterize immunoglobulin G4-related disease (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory features conducted by multidisciplinary physicians of IgG4-RD in Japan. Methods Various specialists retrospectively evaluated IgG4-RD patients diagnosed between 1996 and 2015 in five hospitals by analyzing their baseline clinical features, laboratory, imaging, and pathological test findings, and treatment. Results Of the 334 patients listed, 205 were male and median age at diagnosis was 65 years. The mean number of organs involved was 3.2 at diagnosis. The most frequently affected organs were the salivary glands, followed by the lacrimal glands, lymph nodes, pancreas, retroperitoneum/periaorta, kidneys, and lungs. The mean serum level of IgG4 was 755 mg/dl, and more than 95% of patients had elevated serum IgG4 levels. The median serum level of C-reactive protein (CRP) was 0.1 mg/dl and the level was less than 1 mg/dl in 90% of patients. A total of 34.7% of patients had low serum levels of C3. Serum levels of C3 and non-IgG4 IgG, calculated as the total IgG minus IgG4, showed an inverse correlation in patients with kidney lesions, while serum IgG4 levels were not correlated with serum C3 levels. Corticosteroid was administered in 78.0% of patients, and was effective in all. Conclusions The serum CRP level is generally low and the serum IgG4 level is elevated in most Japanese IgG4-RD patients, in contrast to western patients. These original findings suggest that these two parameters in IgG4-RD differ in some interesting ways from those hitherto reported in western populations. Additional studies, especially international comparative ones, are needed to elucidate the extent and significance of these differences between populations. Attention will also have to be paid to whether the existence of such differences requires consideration when devising international classification criteria. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1467-x) contains supplementary material, which is available to authorized users.

Background Symptomatic differences between male and female patients with IgG4-related disease (IgG4-RD) have been reported [1]. Associations between IgG4-RD and allergy and malignancy have also been reported, although they are controversial. Objectives We previously analyzed the treatment course of IgG4-RD using a multi-center cohort [2]. In the present study, we investigated the associations between organ symptoms and gender, allergic diseases, and malignancies. Methods Data of 166 patients with a definitive diagnosis of IgG4-RD were retrospectively analyzed. Results The cohort consisted of 108 men (65%) and 58 women (35%). Most frequently, the submandibular gland (52%), pancreas (46%), lachrymal gland (43%), and lymph node (38%) were affected. Furthermore, we assessed the frequencies of female sex, allergy, and malignancy in patients with each affected organ (Table 1). The organs with high frequencies of women included the lachrymal gland (50%), lungs (44%), and submandibular gland (43%). Those with low frequencies of women included the thyroid gland (0%), retroperitoneum (17%), and para-aorta (19%). In addition, allergic diseases were found in 60 patients (36%) (Fig. 1A). The organs with high frequencies of allergy included the thyroid gland (50%), submandibular gland (47%), and lachrymal gland (40%). Those with low frequencies of allergy were the para-aorta (13%), prostate gland (30%), and retroperitoneum (31%). Malignancies were found in 23 (14%) patients (Fig. 1B). Organs with high frequencies of malignancy included the para-aorta (38%), prostate gland (30%), and retroperitoneum (21%). In comparison, those with low frequencies of malignancy included the thyroid gland (0%), lungs (8%), and kidney (8%). Conclusion Craniocervical organ involvement was associated with female sex and presence of allergic diseases, suggesting that allergy may contribute to onset of IgG4-RD in some patients. Abdominal organ involvement was associated with male sex and presence of malignancies, suggesting that malignancy may in part contribute to IgG4-RD. Reference [1] Wang, et al., Rheumatology, 2018. [2] Shirakashi, et al., Sci Rep, 2018. Disclosure of Interests Hajime Yoshifuji: None declared, Mirei Shirakashi: None declared, Yuzo Kodama: None declared, Tsutomu Chiba: None declared, Motohisa Yamamoto: None declared, Hiroki Takahashi: None declared, Kazushige Uchida: None declared, Kazuichi Okazaki: None declared, Tetsuya Ito: None declared, Shigeyuki Kawa: None declared, Kazunori Yamada: None declared, Mitsuhiro Kawano: None declared, Shintaro Hirata Grant/research support from: Eli Lilly, UCB, Consultant for: Bristol-Myers Squibb, Jansen, UCB, Paid instructor for: AbbVie, Eisai, Tanabe-Mitsubishi, Speakers bureau: AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, UCB, Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Masafumi Moriyama: None declared, Seiji Nakamura: None declared, Terumi Kamisawa: None declared, Shoko Matsui: None declared, Hiroto Tsuboi: None declared, Takayuki Sumida Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Motoko Shibata: None declared, Hiroshi Goto: None declared, Yasuharu Sato: None declared, Tadashi Yoshino: None declared, Tsuneyo Mimori: None declared

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptom...

ObjectiveIgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes.MethodsWe used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis.ResultsIn the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1–3 (316, 178 and 445 mg/dL, respectively, pConclusionWe identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.

We previously reported that the cytokine profiles in the bronchoalveolar lavage fluid (BALF) of IgG4-related respiratory disease (IgG4-RRD) more closely resemble the T-helper (Th) 2 response than sarcoidosis. The present study aimed to assess the chemokines in the BALF of IgG4-RRD and sarcoidosis in order to evaluate any possible associations between these chemokines and other markers.We examined 12 chemokines using a MILLIPLEX® MAP Kit (Millipore, Darmstadt, Germany) in the same BALF samples of the same 44 patients (IgG4-RRD, n = 11; sarcoidosis, n = 33) in which we had previously evaluated the cytokines.The levels of CC-chemokine ligand (CCL)26 in the BALF of IgG4-RRD patients (median 24.5, range 3.1-401.1 pg/mL) were significantly higher than those in the BALF of sarcoidosis patients (median 3.1, range 3.1-155.6 pg/mL, p 0.05). Interestingly, the BALF levels of CCL1 in the sarcoidosis patients (median 13.1, range 0.1-106.9 pg/mL) were significantly higher than those of the IgG4-RRD patients (median 9.8, range 0.1-14.7 pg/mL, p 0.05). Furthermore, the CCL1 levels in the BALF were correlated with the total cell count (ρ = 0.539, p 0.001), lymphocyte fraction (R = 0.406, P 0.05), lymphocyte count (R = 0.686, P 0.001), TNF-α level, (R = 0.748, P 0.001), and IL-2 level (R = 0.757, P 0.001) in the BALF of sarcoidosis patients.CCL1 might reflect disease activity and its involvement in the pathogenesis of sarcoidosis might be more closely related to Th1 than to Th2.

Aim We conducted a retrospective study to investigate the frequency of appetite loss during treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in elderly patients, aged 75 years or older, with non-small cell lung cancer harboring EGFR gene mutations. Patients and methods Data of a total of 64 patients, including 39 relatively young (hereinafter, younger) patients and 25 elderly patients were analyzed. Results Appetite loss of all grades (p=0.074) and of grade 3 or greater (p=0.030) was more frequently observed in elderly patients. Diarrhea and oral mucositis were also more frequent in elderly patients, although they did not reach statistical significance. No apparent differences were observed in the frequency of aspartate aminotransferase/ alanine aminotransferase elevation, skin rash or fatigue between the two patient groups. The median (95% confidence interval) progression-free survival times were 10.8 (6.6-16.4) months and 11.8 (4.4-20.3) months in the younger and elderly patient groups, respectively. Conclusion Our findings suggest that appetite loss is a major adverse effect in elderly patients with non-small cell lung cancer receiving treatment with EGFR-TKIs.

IgG4-related disease (IgG4-RD) is a recently designated disease entity and its full picture has not yet been elucidated. Here, we report an unusual case of a patient with gastric wall thickening secondary to IgG4-RD. A 68-year-old male visited our hospital with itchy skin lesions and an episode of organizing pneumonia. On the suspicion of malignancy-associated skin lesions, computed tomography (CT) was performed. The CT revealed prominent thickening of the gastric wall. Due to the possibility of malignancy, the patient underwent distal gastrectomy. Histopathological examination showed fibrosis of the submucosa and prominent thickening of the muscularis propria. Most of infiltrating cells were IgG4-positive plasma cells. Post-operative blood test revealed significantly high serum levels of total IgG and IgG4. Based on these histological features, the patient was given a definitive diagnosis of IgG4-RD. Further accumulation of cases like the present case that develop IgG4-RD with rare manifestations would lead to the elucidation of pathogenesis.