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Objective B-cell activating factor (BAFF) is implicated in SLE pathogenesis. Blocking BAFF signalling has contributed to reducing glucocorticoid dosage and preventing organ damage. However, clinical characteristics of patients who may benefit from this therapy are not yet fully elucidated. Therefore, we identified patients with high BAFF-bioactivity to investigate their clinical characteristics and BAFF-producing cells. Methods We established the reporter cell for BAFF and investigated the clinical characteristics of SLE patients with high BAFF-bioactivity. We identified BAFF-expressing kidney cells using publicly available scRNA-seq data and immunohistological analysis. SLE patients were stratified based on the bioactivity of BAFF and type-I IFN (IFN-I) to identify associated characteristic clinical manifestations. Results SLE patients, especially patients with LN, had significantly higher serum BAFF-bioactivity than healthy controls (HC) and non-LN patients. Additionally, single-cell-RNA-seq data and immunohistological analysis of kidney samples from LN patients revealed that BAFF is expressed in glomerular macrophages and mesangial cells. Notably, BAFF bioactivity was elevated in the urine of LN patients compared with that of non-LN patients, while no IFN-I bioactivity was detected in the urine. Furthermore, SLE stratification based on bioactivities of serum BAFF and IFN-I revealed the clinical characteristics of patients: high BAFF represented patients with LN and high IFN-I represented patients with blood and skin manifestations. Conclusions Monitoring urinary BAFF-bioactivity may be valuable in diagnosing LN. Furthermore, stratification based on serum BAFF and IFN-I bioactivities may allow the identification of appropriate patients for biologics targeting BAFF and IFN-I. [ABSTRACT FROM AUTHOR]

Thoracoscopic pleural biopsy is an efficient procedure in patients with undiagnosed exudative pleurisy. Rigid or flexible forceps have been widely used for this procedure. Recently, the use of cryo-techniques was reported in pleural biopsy during semi-rigid thoracoscopy; however, the feasibility and safety of pleural cryobiopsy in elderly patients have not yet been fully elucidated. We describe two elderly patients who safely underwent semi-rigid thoracoscopic cryobiopsy and were diagnosed with tuberculous pleurisy. Both were >85 years of age, and chest auscultation revealed reduced breath sounds in the right lower zones. Laboratory investigations revealed an elevated level of C-reactive protein without leukocytosis in both patients. Computed tomography scan of the chest revealed right pleural effusion in both patients. Pleural fluid biochemical analysis results were indicative of an exudate. Sputum cultures demonstrated no bacterial growth and smears were negative for the presence of acid-fast bacilli. For definitive diagnosis, pleural biopsy was performed via thoracoscopic cryobiopsy. Specimens obtained from the cryoprobe demonstrated 200-300-μm caseating and non-caseating epitheloid cell granulomas with Langerhans type giant cells. Based on the above results, both patients were diagnosed with TB pleurisy. Anti-tuberculosis treatment resulted in good clinical outcome in both patients. Cryobiopsy is easier and more efficient than biopsy with conventional forceps. Our findings in these patients suggest that semi-rigid thoracoscopic cryobiopsy might be a useful alternative diagnostic method for undiagnosed pleural effusion in elderly patients. [ABSTRACT FROM AUTHOR]

Objectives: Autoimmune and allergic diseases are outcomes of the dysregulation of the immune system. Our study aimed to elucidate differences or shared components in genetic backgrounds between autoimmune and allergic diseases., Methods: We estimated genetic correlation and performed multi-trait and cross-population genome-wide association study (GWAS) meta-analysis of six immune-related diseases: rheumatoid arthritis, Graves' disease, type 1 diabetes for autoimmune diseases and asthma, atopic dermatitis and pollinosis for allergic diseases. By integrating large-scale biobank resources (Biobank Japan and UK biobank), our study included 105 721 cases and 433 663 controls. Newly identified variants were evaluated in 21 778 cases and 712 767 controls for two additional autoimmune diseases: psoriasis and systemic lupus erythematosus. We performed enrichment analyses of cell types and biological pathways to highlight shared and distinct perspectives., Results: Autoimmune and allergic diseases were not only mutually classified based on genetic backgrounds but also they had multiple positive genetic correlations beyond the classifications. Multi-trait GWAS meta-analysis newly identified six allergic disease-associated loci. We identified four loci shared between the six autoimmune and allergic diseases (rs10803431 at PRDM2 , OR=1.07, p=2.3×10 -8 , rs2053062 at G3BP1 , OR=0.90, p=2.9×10 -8 , rs2210366 at HBS1L , OR=1.07, p=2.5×10 -8 in Japanese and rs4529910 at POU2AF1 , OR=0.96, p=1.9×10 -10 across ancestries). Associations of rs10803431 and rs4529910 were confirmed at the two additional autoimmune diseases. Enrichment analysis demonstrated link to T cells, natural killer cells and various cytokine signals, including innate immune pathways., Conclusion: Our multi-trait and cross-population study should elucidate complex pathogenesis shared components across autoimmune and allergic diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objective Patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT) are at a risk of CO 2 retention because of excessive oxygen administration. The CapnoEye™ is a novel portable capnometer that can measure end-tidal CO 2 (EtCO 2 ) noninvasively. This retrospective study evaluated the usefulness of this device. Methods EtCO 2 was measured using the CapnoEye™. The EtCO 2 and partial pressure of venous carbon dioxide (PvCO 2 ) were analyzed, and other clinical data were assessed. Patients Sixty-one consecutive patients with chronic respiratory failure receiving LTOT in the outpatient department at the Japanese Red Cross Medical Center between July 2017 and March 2018 were retrospectively reviewed. Results There was a significant correlation between EtCO 2 and PvCO 2 (r=0.63) in the total study population as well as in the COPD group (r=0.65) and ILD group (r=0.67). The PvCO 2 and EtCO 2 gradient was correlated with only the body mass index in a multivariate analysis (p=0.0235). The EtCO 2 levels on the day of admission were significantly higher than those in the same patients when they were in a stable condition (p=0.0049). There was a significant correlation between ΔEtCO 2 and ΔPvCO 2 (r=0.4). A receiver-operating characteristic curve analysis revealed the optimal cut-off EtCO 2 value for identifying hypercapnia to be 34 mmHg (p=0.0005). Conclusion The evaluation of EtCO 2 by the CapnoEye™ was useful for predicting PvCO 2 . The body mass index was identified as a possible predictor of the PvCO 2 and EtCO 2 gradient. An increase in EtCO 2 may indicate deterioration of the respiratory status in patients with chronic respiratory failure receiving LTOT.