Glycan in Nephrology

Simple and complex glycans have been known to play major structural, metabolic, and physiology roles in biological systems. Glycosylation is one of the most common post-translational modification and has an impressive impact on the stability and efficacy of biological therapeutics or biologics. As a famous expert in the antibody market, Creative Biolabs devotes to offering high-quality recombinant antibody products, along with high-level techniques for qualitative and quantitative glycoprotein analysis. Based on our experienced groups, there are flexible, reliable, custom solutions present to studies acquired human diseases clearly, especially nephrology.

Glycans in Chronic Kidney Disease (CKD)

CKD affects 13% adult population in developed countries and relates to increased cardiovascular morbidity and mortality. Heritability estimate research for CKD suggests that post-transcriptional factors may take a critical part in renal damage. IgG is an excellent glycoprotein model because its glycosylation is well defined, and animal assays highlight the potential role of IgG glycosylation in the CKD pathophysiology. A report analyzed IgG glycome composition in a large population-based cohort from the UK and investigated the function of IgG glycosylation in kidneys. The results showed that 14 glycan traits involved in renal function in the discovery sample and remained significant after validation. These glycan traits had three key glycosylation features, sialylation, galactosylation, and a level of bisecting N-acetylglucosamine of IgG glycans. This paper provides a novel insight into the pathogenesis of CKD and promising diagnostic and therapeutic targets.

Fig.1 Oligosaccharyltransferase (OST) complex subunits in mammalians.^{1, 2}

Glycans in IgA Nephrology (IgAN)

IgAN is the most common primary glomerulonephritis around the world, which is identified by mesangial IgA deposits. It is a highly heterogeneous disease, whose pathogenesis is not fully understood till today. Cumulative evidence proved the crucial role of circulating IgA1-containing immune complexes (cIgA1) in the initiation and development of IgAN. The cIgA1 had two major components of galactose-deficient IgA1 (Gd-IgA1) and glycan-specific IgG antibody. In the recent study, IgA1-containing immune complexes and IgG from different individuals were prepared to evaluate the injury of glycan-specific IgG antibody on mesangial cells. The results found that glycan-specific IgG antibodies from IgAN patients had the biological effect to induce the proliferation of mesangial cells. Also, a method had been established for in vitro preparation of IgG-ddIgA1 complexes to help further explore IgAN pathogenesis.

Fig.2 N-glycosylation-mediated mechanisms regulating pathophysiological functions in platelets and megakaryocytes.^{1, 2}

Loss of Sialic Acids in Nephrotic Syndrome

Nephrotic syndrome arises when the glomerulus fails to retain serum proteins during original filtration of plasma, permitting these proteins to leak into the urine. The epithelial mucin molecule named podocalyxin on the foot processes of glomerular podocytes helps to sustain pore integrity and expel proteins from the glomerular filtrate. Sialic acids on podocalyxin are pivotal for such function. In children and nephrotic syndromes that follow bacterial infections, loss of glomerular sialic acid is seen in spontaneous minimal-change renal diseases. As well, animal models seem to imitate this situation with proteinuria and renal failure developing in a dose-dependent manner after once injection of vibrio cholerae sialidase, correlated with loss of sialic acids from kidney glomerulus.

References:

1. Mammadova-Bach, Elmina, et al. "Platelets and defective N-glycosylation." International journal of molecular sciences 21.16 (2020): 5630.
2. Distributed under Open Access license CC BY 4.0, without modification.