Association of the IgGN-glycome with the course of kidney function in type 2 diabetes

Abstract

IntroductionInflammatory processes are thought to be involved in kidney function decline in individuals with type 2 diabetes. Glycosylation of immunoglobulin G (IgG) is an important post-translation process affecting the inflammatory potential of IgG. We investigated the prospective relationship between IgG N-glycosylation patterns and kidney function in type 2 diabetes.Research design and methodsIn the DiaGene study, an all-lines-of-care case–control study (n=1886) with mean prospective follow-up of 7.0 years, the association between 58 IgG N-glycan profiles and estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) per year and during total follow-up was analyzed. Models were adjusted for clinical variables and multiple comparisons.ResultsEleven traits were significantly associated with eGFR change per year. Bisecting GlcNAc in fucosylated and fucosylated disialylated structures and monosialylation of fucosylated digalactosylated structures were associated with a faster decrease of eGFR. Fucosylation of neutral and monogalactosylated structures was associated with less eGFR decline per year. No significant associations between IgG glycans and ACR were found.ConclusionsIn type 2 diabetes, we found IgG N-glycosylation patterns associated with a faster decline of kidney function, reflecting a pro-inflammatory state of IgG. eGFR, but not ACR, was associated with IgG glycans, which suggests these associations may represent renal macroangiopathy rather than microvascular disease.

Proteomic Research in Peritoneal Dialysis

“…In an effort to better predict and formulate treatment to prevent and/or delay diabetic kidney function deterioration, recent studies have identified a strong association between type 2 diabetes and N-linked glycosylation of proteins [74,75]. In particular, the presence of glycosylated immunoglobulin G (IgG), glycosylation of which affects the inflammatory potential of IgG, was prospectively evaluated in the DiaGene study over a mean follow-up of 7 years in a large cohort of diabetic patients [75]. Thereafter, the association was evaluated between 58 IgG N-glycan profiles and the estimated glomerular filtration rate (eGFR) as well as albumin-to-creatinine ratio (ACR).…”

“…[73] Glycosylation profile Type 2 diabetes Different IgG N-glycosylation patterns in diabetes. [75] MALDI-TOF-MS and glycosylation profile Different PD solutions over time Increase of an IgG glycosylation pattern over time and in peritonitis. [67] 2DE and SELDI-TOF-MS Peritonitis Increased in peritonitis: B2M.…”

Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis

“…An increase in antennary fucosylation of α 1 -acid glycoprotein was related with vascular complications in patients with type 1 diabetes [ 23 ]. In patients with type 2 diabetes, a faster decline of kidney functions was associated with IgG glycans containing more bisecting GlcNAc and increased fucosylation with bisecting GlcNAc, whereas fucosylation without bisecting GlcNAc was associated with a slower kidney deterioration [ 24 ]. Inhibition of core-fucosylation alleviated kidney damage and fibrosis in a diabetic mouse model [ 25 ].…”

Variation of IgG N‐linked glycosylation profile in diabetic retinopathy

“…7,8 Bisecting N-acetylglucosamine (GlcNAc) and complex N-glycan structures exert a pro-inflammatory effect, while the addition of galactose, sialic acid, or fucose has an antiinflammatory effect. 9 Recently, variations in IgG glycans have emerged as potential biomarkers and therapeutic targets of various metabolic diseases, such as aging, 10 dyslipidemia, 11 immune disease, 12 type 2 diabetes, 13,14 and diabetic nephropathy. 9 In fact, type 2 diabetes is accompanied by glucose metabolic disorder and imbalanced regulation of inflammation.…”

“…9 Recently, variations in IgG glycans have emerged as potential biomarkers and therapeutic targets of various metabolic diseases, such as aging, 10 dyslipidemia, 11 immune disease, 12 type 2 diabetes, 13,14 and diabetic nephropathy. 9 In fact, type 2 diabetes is accompanied by glucose metabolic disorder and imbalanced regulation of inflammation. Moreover, IgG glycosylation profiles interact with risk factors for type 2 diabetes, such as obesity, 15 blood pressure, 16,17 and FBG.…”