Analysis of Clinical Characteristics and Risk Factors of Plastic Bronchitis in Children With Mycoplasma pneumoniae Pneumonia

Objective: To analyze the clinical characteristics of plastic bronchitis (PB) in children with Mycoplasma pneumoniae pneumonia (MPP) in order to explore its risk factors.Methods: A retrospective analysis was performed in MPP children receiving bronchoscopy admitted to department of respiratory medicine in Shanghai Children's Hospital from January 2018 to December 2020. According to the bronchoscopic findings, the patients were divided into PB group and non-PB group. The clinical manifestations, laboratory examination, etiology, treatment methods and outcomes of the children were analyzed. Logistic regression was used to analyze the risk factors for PB in children with MPP.Results: A total of 296 children with MPP were enrolled in the study, including 42 (14.2%) children in the PB group and 254 (85.8%) children in the non-PB group. There was no difference in the ratios of gender, age, proportion of fever, cough, wet rales, and wheezing rales between the two groups (P > 0.05). The univariate analysis showed that there were significant differences between the PB group and the non-PB group in LDH, D-dimer, CD3+CD4+(%), CD3+CD4+/CD3+CD8+, CD3 count, CD4 count, CD8 count, complement 3, IL8, IL-1β, IL-2, IL-10 (P < 0.05). The multivariate logistic regression analysis showed that fever duration > 12 d, IL-8 > 2,721.33 pg/ml, LDH > 482 U/L and complement 3 <1.02 g/L were independent risk factors for PB in children with MPP.Conclusions: Children with PB caused by MPP have protracted fever, a strong inflammatory response and immune function disturbance.

Dysbiosis of Fecal Microbiota From Complement 3 Knockout Mice With Constipation Phenotypes Contributes to Development of Defecation Delay

Significant phenotypes for constipation were detected in complement 3 (C3) knockout (KO) mice, although no research has been conducted on an association with alteration of gut microbiota. To investigate the effects of dysbiosis on fecal microbiota from C3 KO mice with constipation, the composition of fecal microbiota was characterized in mid-colons of 16-week-old C3 KO mice, and their function for defecation delay development was examined after fecal microbiota transplantation (FMT) of C3 KO mice. Some significant alterations in constipation phenotypes, including stool parameters and histopathological structure, were detected in 16-week-old C3 KO mice compared to those of wild-type (WT) mice. Fecal microbiota of C3 KO mice exhibited decreases in Anaerocolumna, Caecibacterium, Christensenella, Kineothrix, and Oscillibacter populations and increases in Prevotellamassilia, Reuthenibacterium, Prevotella, Eubacterium, Culturomica, Bacteroides, and Muribaculum populations. In FMT study, key stool parameters, including weight and water content, were remarkably declined in a transplanted KO (KFMT) group of antibiotics-induced depletion of microbiota (AiDM)-WT and AiDM-KO mice, and a similar change was observed in fecal morphology. However, intestine length decreased in only the KFMT group of AiDM-WT mice compared with that of AiDM-KO mice. The mucosal layer and muscle thickness were commonly decreased in the KFMT group of AiDM-WT and AiDM-KO mice, and significant alterations in the crypt structure of Lieberkuhn and molecular regulators, including AQP8, C-kit, and 5-HT, were observed in the same group. Taken together, results of the present study indicate that dysbiosis of fecal microbiota from C3 KO mice with constipation phenotypes has a key role in the induction and regulation of defecation delay.

Complement 3 could be available marker of liver function evaluation in patients with hepatitis B virus related cirrhosis and independent predictor of poor outcome in decompensated

Aim Hepatocytes biosynthesize about 80–90% of plasma complement proteins, including complement 3 (C3) and 4 (C4). The purpose of our study is to research the significance of complement in hepatitis B virus related cirrhosis (HBV-cirrhosis), discuss whether C3 and C4 could be served as available markers to assess liver function and prognostic in HBV-cirrhosis. Methods Blood samples were captured from 306 adult patients with HBV-cirrhosis, 23 chronic hepatitis B (CHB) without cirrhosis or liver failure, and 12 healthy adults. Serum C3 and C4 levels were compared in different groups, evaluating the correlation between C3/C4 levels and disease severity in patients with HBV-cirrhosis, analyzing the significance of complement components in infection and mortality of decompensated HBV-cirrhosis. Results The concentrations of C3 and C4 were markedly decreased in HBV-cirrhosis group than those in Chronic Hepatitis B (CHB) and healthy group (p < 0.05, respectively), especially in decompensated stage. In HBV-cirrhosis, The C3 and C4 levels were significantly negatively correlated with International Normalized Ratio (INR) and bilirubin, and significantly positively correlated with albumin, cholinesterase, cholesterol and platelet (p < 0.05, respectively). In addition, these were significance negative correlation with Child-Pugh score (C-P score), End-stage Liver Disease score (MELD score) and AST to platelet ratio (p < 0.05, respectively). More importantly, the C3 were significantly reduced in decompensated HBV-cirrhosis with infection or death, multivariate Cox-regression analysis revealed that lower C3 level was independent predictor of mortality in decompensated HBV-cirrhosis. Conclusions The C3 level could be served as available follow-up marker to evaluate liver function and disease severity in HBV-cirrhosis and superior to C4. Decreased C3 might be independent poor prognostic factor in patients with decompensated HBV-cirrhosis.

POS0417 EXOGENOUS CXCL5 RESTORES ENDOGENOUS BLOOD-TISSUE CHEMOKINE GRADIENT TO IMPROVE SURVIVAL IN MURINE LUPUS

Background:Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that is potentially fatal. There is an unmet need to improve current therapies. In patients with SLE, we observed that serum CXCL5 levels were significantly lower than healthy control subjects and negatively correlated with disease activity(1-9).Objectives:The aim of this study is to elucidate the effect of supplemental serum CXCL5 in abrogating the pathological processes of SLE.Methods:Ten doses of exogenous CXCL5 (3µg/kg) was administered to 16-week-old Faslpr mice weekly by intravenous injection. Mice were monitored for 10 weeks. Splenic immune profile was measured by flow cytometry. Circulating cytokine and immunoglobulin profile were detected by Luminex technology. Renal function was evaluated by urinary spot albumin creatinine ratio. In situ renal immune cell infiltration and complement 3 deposition were detected by Haematoxylin and Eosin (H&E) and immunohistochemistry staining. The molecular pathways involved were examined by RNA sequencing.Results:In Faslpr mice, intravenous administration of exogenous CXCL5 significantly improved mouse survival with concomitant reduction of autoantibody secretion, proteinuria, complement 3 deposition, neutrophil infiltration and lupus nephritis classes. Through evaluating the changes of immune profile, cytokine profile and molecular pathways, we found that intravenous CXCL5 reduced inflammation via an orchestral effect of regulating neutrophil trafficking and modulating helper T cell-mediated immune response. Pharmacokinetic and real-time Polymerase Chain Reaction studies further demonstrated that this orchestration was triggered by a cascade reaction - restoring vascular under-expressed CXCL5 by an exogenous stimulation, re-establishing the normal serum levels of endogenous CXCL5 and reverting the CXCL5 chemokine gradient between inflamed tissues and blood circulation.Conclusion:Managing the dysregulation of CXCL5 by exogenous supplement may provide a new option for SLE therapy.References:[1]Dufies M, Grytsai O, Ronco C, et al. New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments. Theranostics. 2019;9(18):5332-5346. doi:10.7150/thno.34681[2]Yildirim K, Colak E, Aktimur R, et al. Clinical Value of CXCL5 for Determining of Colorectal Cancer. Asian Pac J Cancer Prev. Sep 26 2018;19(9):2481-2484. doi:10.22034/apjcp.2018.19.9.2481[3]Wu K, Yu S, Liu Q, Bai X, Zheng X. The clinical significance of CXCL5 in non-small cell lung cancer. Onco Targets Ther. 2017;10:5561-5573. doi:10.2147/ott.s148772[4]Zhao J, Ou B, Han D, et al. Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3beta/beta-catenin pathways. Mol Cancer. Mar 29 2017;16(1):70. doi:10.1186/s12943-017-0629-4[5]Han KQ, Han H, He XQ, et al. Chemokine CXCL1 may serve as a potential molecular target for hepatocellular carcinoma. Cancer Med. Oct 2016;5(10):2861-2871. doi:10.1002/cam4.843[6]Pappa CA, Tsirakis G, Kanellou P, et al. Monitoring serum levels ELR+ CXC chemokines and the relationship between microvessel density and angiogenic growth factors in multiple myeloma. Cytokine. Dec 2011;56(3):616-20. doi:10.1016/j.cyto.2011.08.034[7]Zhang L, Li H, Ge C, et al. CXCL3 contributes to CD133(+) CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation. Sci Rep. Jun 3 2016;6:27426. doi:10.1038/srep27426[8]Matsubara J, Honda K, Ono M, et al. Reduced plasma level of CXC chemokine ligand 7 in patients with pancreatic cancer. Cancer Epidemiol Biomarkers Prev. Jan 2011;20(1):160-71. doi:10.1158/1055- 9965.epi-10-0397[9]Ma Y, Ren Y, Dai ZJ, Wu CJ, Ji YH, Xu J. IL-6, IL-8 and TNF-alpha levels correlate with disease stage in breast cancer patients. Adv Clin Exp Med. May-Jun 2017;26(3):421-426. doi:10.17219/acem/62120Disclosure of Interests:None declared

Serum complement 3 is a potential biomarker for assessing disease activity in Takayasu arteritis

Background Takayasu arteritis (TA) is a rare disease, lacking convenient and feasible biomarkers to identify disease activity. We aimed to evaluate the value of complements in distinguishing active TA. Methods Consecutive patients were enrolled from the prospective East China TA cohort from April 2008 to June 2019. Patients were divided into two groups according to their baseline Kerr score. The value of complements and other biomarkers in identifying disease activity were analysed with cluster analysis, ROC curves, and combined tests. An independent group of patients from July 2019 to December 2019 were employed to validate the results. Results Of the enrolled 519 patients, 406 (72.2%) cases were identified as active disease. Higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), and complement 3 (C3) levels were observed in the active group. Elevated C3 (≥ 1.085 g/L) had a high value to identify active TA with a sensitivity of 69.9%, specificity of 66.7%, and AUC of 0.715. Combining the CRP (≥ 10.65 g/L; sensitivity, 50.7%; specificity, 82.4%) and C3, the sensitivity could be improved to 85.1% in parallel test and the specificity could be improved to 94.1% in serial test. Validation was further performed to confirm the value of C3 for disease activity assessment. The accuracy of the parallel test of CRP and C3 in external validation with independent 53 TA cases was 72.73% with the AUC of 0.721. Conclusion Elevated C3 could effectively evaluate the disease activity of TA, and C3 combining with CRP could further improve the disease activity evaluation.

Fibrillary glomerulonephritis or complement 3 glomerulopathy: a rare case of diffuse necrotising crescentic glomerulonephritis with C3-dominant glomerular deposition and positive DNAJB9

Fibrillary glomerulonephritis (FGN) and complement 3 glomerulopathy (C3G) are rare forms of glomerulonephritis with distinct aetiologies. Both FGN and C3G can present with nephritic syndrome. FGN is associated with autoimmune disease, dysproteinaemia, malignancy and hepatitis C infection. C3G is caused by the unregulated activation of the alternative complement pathway. We present a rare case of diffuse necrotising crescentic glomerulonephritis with dominant C3 glomerular staining on immunofluorescence—consistent with C3G—but electron microscopy (EM) findings of randomly oriented fibrils with a mean diameter of 14 nm and positive immunohistochemistry for DNAJB9—suggestive of FGN. To the best of our knowledge, this is the first reported case of FGN to show dominant C3 glomerular deposits. This case report reaffirms the utility of EM in the evaluation of nephritic syndrome and highlights the value of DNAJB9—a novel biomarker with a sensitivity and specificity near 100% for FGN.