IntroductionSeveral epidemiological studies have shown that silica exposure triggers the onset of systemic lupus erythematosus (SLE); however, the clinical characteristics of silica-associated SLE have not been well studied.Patient concernsA 67-year-old man with silicosis visited a primary hospital because of a fever and cough. His respiratory condition worsened, regardless of antibiotic medication, and he was referred to our hospital.DiagnosisThe patient showed leukopenia, lymphopenia, serum creatinine elevation with proteinuria and hematuria, decreased serum C3 level, and was positive for anti-double stranded DNA antibody, anti-nuclear antibody, and direct Coombs test. He was diagnosed with SLE. Renal biopsy was performed, and the patient was diagnosed with lupus nephritis (class IV-G(A/C) + V defined by the International Society of Nephrology/Renal Pathology Society classification). Computed tomography revealed acute interstitial pneumonitis, bronchoalveolar lavage fluid showed elevation of the lymphocyte fraction, and he was diagnosed with lupus pneumonitis.InterventionsPrednisolone (50 mg/day) with intravenous cyclophosphamide (500 mg/body) were initiated.OutcomesThe patient showed a favorable response to these therapies. He was discharged from our hospital and received outpatient care with prednisolone slowly tapered off. He had cytomegalovirus and herpes zoster virus infections during treatment, which healed with antiviral therapy.Review:We searched for the literature on sSLE, and selected 11 case reports and 2 population-based studies. The prevalence of SLE manifestations in sSLE patients were comparative to that of general SLE, particularly that of elderly-onset SLE. Our renal biopsy report and previous reports indicate that lupus nephritis of sSLE patients show as various histological patterns as those of general SLE patients. Among the twenty sSLE patients reported in the case articles, three patients developed lupus pneumonitis and two of them died of it. Moreover, two patients died of bacterial pneumonia, one developed aspergillus abscesses, one got pulmonary tuberculosis, and one developed lung cancer.ConclusionClose attention is needed, particularly for respiratory system events and infectious diseases, when treating patients with silica-associated SLE using immunosuppressive therapies.

Background The primary objective of this phase I, open-label trial was to assess safety and tolerability of tremelimumab monotherapy and combination therapy with durvalumab in Japanese patients with advanced cancer. Tremelimumab is a fully human monoclonal antibody against CTLA-4 in clinical trials; durvalumab is a monoclonal antibody against PD-L1 for the treatment of bladder and lung cancer. Methods In part 1, tremelimumab 3 or 10 mg/kg was given every 4 weeks (Q4W) for 6 doses, and thereafter every 12 weeks until discontinuation (n = 8); subsequently tremelimumab 10 mg/kg Q4W for 6 doses/Q12W and thereafter until discontinuation was administered in 41 patients with malignant pleural or peritoneal mesothelioma (MPM). In part 2, tremelimumab 10 mg/kg (Q4W for 6 doses followed by Q12W for 3 doses) was given in combination with durvalumab 15 mg/kg (Q4W for 13 doses) in cohort 1 (n = 4). In cohort 2 (n = 6), tremelimumab 1 mg/kg (Q4W for 4 doses) was given in combination with durvalumab 20 mg/kg (Q4W for 4 doses followed by 10 mg/kg Q2W for 22 doses), while in cohort 3 (n = 6), fixed-dose tremelimumab 75 mg Q4W for 4 doses plus durvalumab 1500 mg Q4W for 13 doses was given. Results In part 1, no dose-limiting toxicities (DLTs) for tremelimumab 3 or 10 mg/kg (Q4W for 6 doses/Q12W thereafter until discontinuation) were observed. Six (75%) patients reported treatment-related adverse events (trAEs). In the MPM dose-expansion cohort, 38 (92.7%) patients reported trAEs. In part 2, one DLT (Grade 4 myasthenia gravis) was reported for tremelimumab 10 mg/kg (Q4W for 6 doses/Q12W for 3 doses) plus durvalumab 15 mg/kg (Q4W for 13 doses). One DLT (Grade 4 hyperglycemia) was reported for tremelimumab 75 mg (Q4W for 4 doses) plus durvalumab 1500 mg (Q4W for 13 doses). Fourteen (87.5%) patients reported trAEs. Tremelimumab demonstrated low immunogenicity; 1 (16.7%) patient developed antidrug antibodies. Conclusion Tremelimumab 10 mg/kg (Q4W/Q12W), tremelimumab 1 mg/kg (Q4W) plus durvalumab 20 mg/kg (Q4W/10 mg/kg Q2W), and fixed-dose tremelimumab 75 mg (Q4W) plus durvalumab 1500 mg (Q4W) were safe and tolerable. ClinicalTrials.gov Identifier: NCT02141347 (https://clinicaltrials.gov/ct2/show/NCT02141347)

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Background Secretory leukocyte peptidase inhibitor (SLPI) is a biomarker present in the respiratory tract that protects against tissue destruction and aids wound healing. However, it is difficult to distinguish early-stage malignant pleural mesothelioma (MPM) from benign asbestos pleural effusion (BAPE) presenting as pleural effusion in diagnostic imaging. More biomarkers of pleural effusion are needed to identify early-stage MPM. We examined whether SLPI in pleural effusion can be used to distinguish BAPE from MPM and other conditions that involve pleural effusion. Methods We measured levels of SLPI, hyaluronic acid (HA), soluble mesothelin-related peptides (SMRP), galectin-3, CCL2, and CYFRA21-1 in 51 BAPE patients, 37 MPM patients, 77 patients with pleural effusions due to non-small cell lung cancer (LCa), and 74 patients with other pleural effusions diagnosed at Okayama Rosai Hospital. Results SLPI levels in pleural fluid of BAPE patients were significantly lower (p < 0.0001) than those in patients with MPM, LCa, and other pleural effusions. The area under curve (AUC) for SLPI’s ability to distinguish BAPE from MPM was 0.902, with a sensitivity of 82.4% and a specificity of 86.5%. These values were not only favorable, but were better than the AUC for the ability to distinguish BAPE from HA (0.802), and SMRP (0.746). Galectin-3 levels were significantly lower in patients with BAPE compared with those in patients with MPM and the other two diseases, whereas CCL2 levels were significantly higher in patients with BAPE compared with patients with MPM and the other two diseases. Moreover, CYFRA21-1 levels were significantly lower in BAPE patients compared with levels in patients with MPM and LCa. Using these six markers enabled BAPE to be distinguished from MPM and other diseases. As a single marker, SLPI proved to be superior to HA and SMRP for the diagnosis of BAPE. Conclusions The measurement of pleural fluid SLPI as well as HA and SMRP is useful as a biomarker to diagnose BAPE, which needs to be distinguished from early-stage MPM.

Background: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. Methods: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. Results: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM patients. Conclusions: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.