Neutrophil extracellular trap formation is associated with autophagy-related signalling in ANCA-associated vasculitis.

Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti-lysosomal membrane protein-2 (LAMP-2) antibody, may have a pathogenic role in AAV. We have shown previously that anti-LAMP-2 antibody-stimulated NET formation contains autoantigens and anti-microbial peptides. The current study sought to determine whether LAMP-2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti-LAMP-2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti-LAMP-2 antibody-induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP-2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti-LAMP-2 antibody, and this effect was attenuated by the inhibitors of autophagy 3-methyladenine (3MA) and 2-morpholin-4-yl-8-phenylchromen-4-one (LY294002). The anti-LAMP-2 antibody-stimulated NET formation was unaffected by benzyloxycarbonyl-Val- Ala-Asp (OMe)-fluoromethylketone (zVAD-fmk) and necrostatin-1 (Nec-1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P=0.0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti-LAMP-2 antibody. Our results provide further evidence that autophagy is involved in ANCA-induced NET formation in human neutrophils.

Investigation of the clinical significance of detecting PTX3 for community-acquired pneumonia.

OBJECTIVE: To evaluate the value of PTX3 in the diagnosis of community-acquired pneumonia (CAP). PATIENTS AND METHODS: We included 170 inpatients diagnosed with CAP from January 2016 to December 2018. The patients were divided into the severe pneumonia group and the mild pneumonia group according to their condition. According to the results of pathogen detection, they were divided into the bacterial infection group, the virus infection group, the mixed infection group, and the other pathogen infection group. Clinical data including C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), and neutrophil-lymphocyte ratio (NLR) were collected. Blood was collected within 24 hours, 3 days, and 7 days after admission, and the serum PTX3 level was dynamically monitored. The correlation between different groups was compared, and expression differences and dynamic changes of PTX3 were analyzed. RESULTS: PTX3, PCT, and CRP in the CAP group were higher than those in the healthy control group, and the difference was statistically significant (p<0.05). Compared with the mild group, the increase of PTX3, PCT, and CRP was also different in the severe group (p<0.05). The area under the ROC curve of PTX3 was 0.726 (sensitivity 76.08%, specificity 76.92%) when the threshold value was 32.26 ng/ml. Dynamic monitoring of PTX3 showed that the PTX3 level in severe CAP patients was significantly higher than that in mild patients (p<0.05), and the PTX3 level in both groups gradually decreased with treatment time, but the level in severe CAP patients remained at a high level on the 7th day. The main pathogens in CAP were bacteria (77 cases, 45.7%), and there was no significant difference in the PTX3 level among the patients infected with different pathogenic bacteria (p=0.311). CONCLUSIONS: The serum PTX3 level, especially the dynamic monitoring results, can be used as a biomarker to reflect community acquired pneumonia, which can provide effective auxiliary diagnosis and efficacy in monitoring for clinical practice.

Tuberculosis-associated mortality and its risk factors in a district of Shanghai, China: a retrospective cohort study.

SETTING: Pulmonary tuberculosis (PTB) causes a considerable number of deaths in China; however, the factors related to mortality are not well known. OBJECTIVE: To determine mortality among PTB patients and to explore its risk factors in Shanghai, China. DESIGN: This was a retrospective population-based study. A cohort of PTB patients who initiated treatment in a district of Shanghai from 2004 to 2015 was evaluated. Mortality in PTB patients was studied using the standardised mortality ratio (SMR) and Cox's proportional hazards model. RESULTS: Of 2741 PTB patients recruited in our study, 394 (14.4%) died during the 12-year follow-up. The summarised SMR was 2.8, and death was most likely to occur during the first months of anti-tuberculosis treatment. Age 60 years (adjusted hazard ratio [aHR] 4.039, P < 0.001), male sex (aHR 1.603, P < 0.001), sputum smear test positivity (aHR 1.945, P < 0.001), multidrug-resistant TB (MDR-TB; aHR 3.502, P = 0.001), diabetes mellitus (aHR 1.422, P = 0.012), chronic obstructive pulmonary disease (aHR 2.505, P < 0.001) and having cancer (aHR 4.319, P < 0.001) were risk factors for PTB mortality. CONCLUSION: The overall mortality in PTB patients was higher than that in the general population. MDR-TB and comorbidity were the two leading risk factors for mortality in PTB patients. Early, accurate diagnosis, together with comprehensive management and treatment, can reduce the mortality rate in PTB patients.

Disseminated penicilliosis marneffei in China. Report of three cases.

Three cases with disseminated Penicilliosis marneffei (PSM) are reported. They are all natives of Guangxi Zhuang Autonomous Region. Among them, 2 died and 1 remains alive. Their clinical features were characterized by multiple organ involvement, multiple subcutaneous abscesses, inflammatory papules, nodules and pustulae, and enlargement of superficial lymph nodes with chills, fever, anemia and leukocytosis. The mycology and histopathology of PSM are also discussed. The authors propose that the medical profession in Guangxi should be vigilant against the disease and reduce the mortality by early diagnosis and treatment.