Early Diagnosis of Tuberculosis-Associated IgA Nephropathy with ESAT-6

Abstract

IgA nephropathy (IgAN) is the most common cause of primary renal diseases worldwide, and the early secreted antigenic target of 6 (ESAT-6) which was secreted by Mycobacterium tuberculosis (MTB) may be involved in the development and progression of IgAN. This study aimed to investigate the role of ESAT-6 for early diagnosis of IgAN caused by MTB infection. From 2011 to 2014, 21 patients with renal tuberculosis (RTB), 25 with IgAN, and 46 with IgAN infected with MTB (IgAN/MTB) were enrolled. Serum levels of antibodies against Mycobacterium tuberculosis antigen 85A (Ag85A) were measured by ELISA. Urine culture and phage amplified biologically assay were performed to detect MTB. HE staining was used to observe the morphological changes in kidney tissues. Immunohistochemistry was applied to detect the expression of ESAT-6. Immunofluorescence staining was conducted to detect IgA1. Positive rates of serum anti-Ag85A antibody and urine culture for MTB were higher in the RTB and IgAN/MTB groups than those in the IgAN group. The positive rates of plaques were also higher in RTB and IgAN/MTB groups than the positive rate in the IgAN group. By contrast, the positive rate of ESAT-6 was lower in the IgAN group than that in the RTB group or the IgAN/MTB group, whereas the expression levels of IgA1 were higher in the IgAN and IgAN/MTB groups, compared with the RTB group. Our findings suggest that ESAT-6 and IgA1 may be helpful for early diagnosis of IgAN caused by MTB infection.

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

“…This is to the exception of IgA-nephropathy, a leading cause of primary kidney disease which is due to deposition of IgA in renal tubules leading to glomerulonephritic disease and eventually CKD. In a cohort of IgA-nephropathic patients co-infected with TB, levels of anti-Ag85A antibody were higher in co-infected patients indicating an ability to generate Mtb-specific antibody (275). It is thought that elevated Mtb-specific IgA levels contribute to IgA nephropathy co-infection, glomerulonephritis and ensuing CKD (276).…”

“…It is thought that elevated Mtb-specific IgA levels contribute to IgA nephropathy co-infection, glomerulonephritis and ensuing CKD (276). The pathogenesis of this involves alternative complement activation, lectin activation and deposition of IgA-complexes in the kidney (275,276). Deposits of IgA1 are found at higher levels of coinfected individuals as well as patients presenting with renal TB (275).…”

“…The pathogenesis of this involves alternative complement activation, lectin activation and deposition of IgA-complexes in the kidney (275,276). Deposits of IgA1 are found at higher levels of coinfected individuals as well as patients presenting with renal TB (275). Further, high levels of TGF-β1 are correlated with defective IgA1 generation and TGF-β1 increases in both TB and IgA nephropathy (276).…”

“…Studies assessing Mtb proteins and kidney injury found the Mtb antigen, ESAT-6, contributed to renal injury in mice injected with a high dose of ESAT-6 by upregulating the expression of pro-inflammatory microRNA-155 via the MyD88 innate cell pathway (275,277,278). While the dose of ESAT-6 used in these studies may not reflect those found in physiological disease, this evidence may show a cyclical worsening of disease in CKD/TB coinfection exacerbated by kidney inflammation caused by TB and CKD independently.…”

An outbreak of tuberculosis due toMycobacterium bovisinfection in a pack of English Foxhounds (2016-2017)

“…Other conditions which adversely affect the outcome of renal TB are the deposition of anti‐mycobacterial antibodies within the glomeruli and/or hypercalcaemia which is a common complication of TB and is directly nephrotoxic (Bellendir, Kochanova, & Nakonechny ; Chan et al., ; Ko et al., ; Zhao, Sun, Xu, & Sun, ). It is possible that either of these conditions could have had an impact on the number of dogs affected and the severity of disease seen in this outbreak.…”