Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy

Background The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN). Methods This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-β were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs). Results The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-β in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren’t any significant differences in the levels of IL-6, TNF-α, and TGF-β when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1. Conclusions The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

Utilizing the MEST score for prognostic staging in IgA nephropathy

Background The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. Methods A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). Results The mean follow-up time was 16.5 years (range 0.2–28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. Conclusions Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.

Case Report: Silicosis and IgA nephropathy, an exceptional association

A 57-year-old male who had been working in masonry for 33 years was hospitalized for renal function decline associated with exertional dyspnea. He presented with hypertension and limb edema. Urinalysis revealed an active urine sediment with glomerular proteinuria at 1.5 g/24h and the renal biopsy identified mesangial IgA Nephropathy. Chest tomography scans showed signs of silicosis. The patient received Angiotensin-Converting Enzyme Inhibitors with stable renal function. To our knowledge, the association of silicosis-IgA nephropathy has rarely been reported in the literature. This case highlights the effect of chronic exposure to silica dust and its association with both silica and renal disease.

Title IgA Nephropathy and Oral Bacterial Species Related to Dental Caries and Periodontitis

A relationship between IgA nephropathy (IgAN) and bacterial infection has been suspected. As IgAN is a chronic disease, bacteria that could cause chronic infection in oral areas might be pathogenetic bacteria candidates. Oral bacterial species related to dental caries and periodontitis should be candidates because these bacteria are well known to be pathogenic in chronic dental disease. Recently, several reports have indicated that collagen-binding protein (cnm)-(+) Streptococcs mutans is relate to the incidence of IgAN and the progression of IgAN. Among periodontal bacteria, Treponema denticola, Porphyromonas gingivalis and Campylobacte rectus were found to be related to the incidence of IgAN. These bacteria can cause IgAN-like histological findings in animal models. While the connection between oral bacterial infection, such as infection with S. mutans and periodontal bacteria, and the incidence of IgAN remains unclear, these bacterial infections might cause aberrantly glycosylated IgA1 in nasopharynx-associated lymphoid tissue, which has been reported to cause IgA deposition in mesangial areas in glomeruli, probably through the alteration of microRNAs related to the expression of glycosylation enzymes. The roles of other factors related to the incidence and progression of IgA, such as genes and cigarette smoking, can also be explained from the perspective of the relationship between these factors and oral bacteria. This review summarizes the relationship between IgAN and oral bacteria, such as cnm-(+) S. mutans and periodontal bacteria.