The levels of urinary joining chain containing IgG immune complexes are associated with disease severity in IgA nephropathy

Abstract

Background: Circulating levels of aberrantly glycosylated IgA1 and its immune complexes (IgA/IgG-IC) are elevated and correlated with disease severity in IgA nephropathy (IgAN). The pathologic IgA containing immune complexes deposits in the kidney were found to be in dimeric or polymeric forms, suggesting that those deposited IgA immune complexes contain joining chain, which is critical for the multimerization and transportation of IgA. Both the dimeric IgA and polymeric IgA can cause renal damage by inducing the release of cytokines from mesangial cells. We aimed to investigate the urinary J chain containing IgG immune complexes/creatinine ratio (UJGCR) and analyze its relationship with disease severity in IgAN. Methods: The UJGCR were measured by sandwich enzyme linked immunosorbent assay in 26 patients with IgAN, 31 patients with other kidney diseases and 32 healthy volunteers. Results: The levels of UJGCR were higher in patients with IgAN than that in non-IgAN patients ( P =0.006) and healthy volunteers ( P <0.0001). Importantly, receiver operating characteristics curve analysis confirmed that UJGCR had good discrimination between non-IgAN patients and IgAN patients. The levels of UJGCR positively correlated with 24-hour urinary protein excretion (r=0.63, P =0.0006), serum creatinine (r=0.55, P =0.003), and negatively correlated with estimated glomerular filtration rate (r= -0.61, P =0.0008) in IgAN. Furthermore, the levels of UJGCR were higher in IgAN patients with IgA mesangial deposition of (+/++) than patients with (+++/++++). And IgAN patients with tubular atrophy/interstitial fibrosis showed higher levels of UJGCR than that without ( P =0.03). Similarly, the levels of urinary IgA-IgG/creatinine ratio (UAGCR) were also found to be elevated and associated with clinical and pathological parameters as UJGCR in IgAN. Besides, significant correlation between the levels of UJGCR and UAGCR was shown, suggesting UJGCR was mainly composed of J-IgA-IgG. Conclusions: The levels of UJGCR are associated with disease severity in IgAN. UJGCR is a potential biomarker for both glomerular and tubulointerstitial lesions in IgAN.