National Natural Science Foundation of China and the National Key Research and Development Program of China.

Previous studies have associated ambient particulate chemical constituents with adverse cardiopulmonary health effects. However, specific pollution sources behind the cardiopulmonary health effects of ambient particles are uncertain. We examined the cardiopulmonary health effects of fine particles (PM2.5) from different pollution sources in Beijing, China, among a panel of 40 healthy university students. Study subjects were repeatedly examined for a series of cardiopulmonary health indicators during three 2-month-long study periods (suburban period, urban period 1, and urban period 2) in 2010-2011 before and after relocating from a suburban campus to an urban campus with changing air pollution levels and contents. Daily ambient PM2.5 mass samples were collected over the study and measured for 29 chemical constituents in the laboratory. Source appointment for ambient PM2.5 was performed using Positive Matrix Factorization, and mixed-effects models were used to estimate the cardiopulmonary effects associated with source-specific PM2.5 concentrations. Seven PM2.5 sources were identified as traffic emissions (12.0%), coal combustion (22.0%), secondary sulfate/nitrate (30.2%), metallurgical emission (0.4%), dust/soil (12.4%), industry (6.9%), and secondary organic aerosol (9.9%). Ambient PM2.5 in the suburban campus had larger contributions from secondary sulfate/nitrate (41.8% vs. 22.9%-26.0%) and metallurgical emission (0.7% vs. 0.3%) as compared to that in the urban campus), whereas PM2.5 in the urban campus had larger contributions from traffic emissions (13.0%-16.3% vs. 5.1%), coal combustion (21.0%-30.7% vs. 10.7%), and secondary organic aerosol (9.7%-12.0% vs. 8.7%) as compared to that in the suburban campus. Potential key sources were identified for PM2.5 effects on inflammatory biomarkers (secondary sulfate/nitrate and dust/soil), blood pressure (coal combustion and metallurgical emission), and pulmonary function (dust/soil and industry). Analyses using another source appointment tool Unmix yielded a similar pattern of source contributions and associated health effects. In conclusion, ambient PM2.5 in Beijing suburban and urban areas has two distinct patterns of source contributions, and PM2.5 from different sources may play important roles on different aspects of PM2.5-related cardiopulmonary health effects.

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Epitopes of phospholipase A2 receptor (PLA2R), the target antigen in idiopathic membranous nephropathy (iMN), must be presented by the HLA-encoded MHC class II molecules to stimulate autoantibody production. A genome-wide association study identified risk alleles at HLA and PLA2R loci, with the top variant rs2187668 within HLA-DQA1 showing a risk effect greater than that of the top variant rs4664308 within PLA2R1. How the HLA risk alleles affect epitope presentation by MHC class II molecules in iMN is unknown. Here, we genotyped 261 patients with iMN and 599 healthy controls at the HLA-DRB1, HLA-DQA1, HLA-DQB1, and HLA-DPB1 loci with four-digit resolution and extracted the encoded amino acid sequences from the IMGT/HLA database. We predicted T cell epitopes of PLA2R and constructed MHC-DR molecule-PLA2R peptide-T cell receptor structures using Modeler. We identified DRB1*1501 (odds ratio, 4.65; 95% confidence interval [95% CI], 3.39 to 6.41; <0.001) and DRB1*0301 (odds ratio, 3.96; 95% CI, 2.61 to 6.05; <0.001) as independent risk alleles for iMN and associated with circulating anti-PLA2R antibodies. Strong gene-gene interaction was noted between rs4664308(AA) and HLA-DRB1*1501/DRB1*0301. Amino acid positions 13 (<0.001) and 71 (<0.001) in the MHC-DR1 chain independently associated with iMN. Structural models showed that arginine13 and alanine71, encoded by DRB1*1501, and lysine71, encoded by DRB1*0301, facilitate interactions with T cell epitopes of PLA2R. In conclusion, we identified two risk alleles of HLA class II genes and three amino acid residues on positions 13 and 71 of the MHC-DR1 chain that may confer susceptibility to iMN by presenting T cell epitopes on PLA2R.

In this study, we measured soluble urokinase receptor levels, a possible permeability factor, in the plasma of patients with primary focal segmental glomerulosclerosis (FSGS) and determined their association with clinical and pathological data in 74 patients with primary FSGS. Healthy donors and patients with minimal change disease, membranous nephropathy, and secondary FSGS were used as controls. The plasma-soluble urokinase receptor levels, measured by commercial ELISA kits, of patients with primary FSGS (median: 2923, interquartile range 2205-4360 pg/ml) were significantly higher than those of patients with minimal change disease (median 2050 pg/ml), membranous nephropathy (median 2029 pg/ml), and normal individuals (median 1739 pg/ml). There was no significant difference in plasma-soluble urokinase receptor levels between the 74 patients with primary and 14 patients with secondary FSGS. The soluble urokinase receptor levels increased in the order of tip variant, to a not otherwise specified variant and a cellular variant. The soluble urokinase receptor levels were significantly but negatively correlated with creatinine clearance at presentation but positively correlated with crescent formation in patients with primary FSGS. During follow-up, receptor levels decreased significantly in patients with complete remission. Thus, plasma-soluble urokinase receptor levels did not differentiate primary and secondary FSGS, and although significantly elevated in FSGS, they showed considerable overlap with other glomerular diseases.