Mesangial deposition of aberrantly glycosylated IgA1 (agIgA1) and its immune complexes is a key pathogenic mechanism of IgA nephropathy (IgAN). However, treatment of IgAN remains ineffective. We report here that bacteria-derived IgA proteases are capable of degrading these pathogenic agIgA1 and derived immune complexes in vitro and in vivo. By screening 14 different bacterial strains (6 species), we found that 4 bacterial IgA proteases from H. influenzae, N. gonorrhoeae and N. meningitidis exhibited high cleaving activities on serum agIgA1 and artificial galactose-depleted IgA1 in vitro and the deposited agIgA1-containing immune complexes in the mesangium of renal biopsy from IgAN patients and in a passive mouse model of IgAN in vitro. In the modified mouse model of passive IgAN with abundant in situ mesangial deposition of the agIgA-IgG immune complexes, a single intravenous delivery of IgA protease from H. influenzae was able to effectively degrade the deposited agIgA-IgG immune complexes within the glomerulus, demonstrating a therapeutic potential for IgAN. In conclusion, the bacteria-derived IgA proteases are biologically active enzymes capable of cleaving the circulating agIgA and the deposited agIgA-IgG immune complexes within the kidney of IgAN. Thus, the use of such IgA proteases may represent a novel therapy for IgAN.

Background Malnutrition is a common clinical problem in peritoneal dialysis (PD) patients and is a predictor of mortality. This work analyzes the effect of nutritional supplementation for PD patients on all‐cause and cardiovascular disease (CVD)‐related deaths by meta‐analysis. Methods A study about nutritional interventions for PD patients on all‐cause or CVD‐related mortality is included. Results Eight studies were included. The results showed that nutritional intervention can reduce all‐cause mortality in PD patients (HR, 0.71; 95% confidence interval (CI), 0.64–0.79; p < 0.01). In CVD‐related mortality, the results also showed that nutritional interventions significantly reduce CVD‐related mortality (HR, 0.75; 95% CI, 0.64–0.87; p < 0.01). In exploratory analysis, vitamin D, folic acid, and high‐plant‐protein ratio intake have relative advantages. Conclusion Appropriate nutritional supplementation to PD patients can effectively reduce all‐cause and CVD‐ related mortality in clinical practice, especially for vitamin D, folic acid, sodium supplements, and a high proportion of plant protein.