Immunoglobulin G (IgG) Glycosylation, Renal Function, and Antibody-Mediated Rejection in Renal Transplant

Abstract

Background: IgG glycome composition is a key regulator of immune system modulating inflammation at multiple levels. It has been associated to aging, infections response, autoimmune diseases or early kidney failure. Its role in KT has not been studied. Our aim was to analyze the prognostic and diagnostic value of IgG_glycans in renal function after 1year of KT and in antibody-mediated rejection (AMR) Methods: We analyzed 24 essential IgG glycans by Highperformance Liquid Chromatography grouped them by biological function, according to the proportion of Galactosylated, Agalactosylated, Sialicylated, Fucosylated and Bisecting-GlcNAc structures. We measured baseline IgG_glycans and one year after KT in 248 recipients (62%M:38%M) of 55.9±13.6 years, 36 with AMR. Association models were adjusted by donor characteristics, baseline renal function, age/sex, BMI, ATN-postKT and comorbidities Results: Differences between IgG_glycans at baseline and 1year values were associated with the achieved renal function: Higher Sialization (Coeff [95% CI] 2.07 [0.23-0.3.9]) and Galactosylation (1.84 [0.0-3.6]), the better renal function and higher proportion of agalactosylated glycans associated worse renal function -2.02 [-4.1- -0.34]. AMR occurred more frequently in patients with a higher proportion of Agalactosylated glycans (OR [95% CI]) 1.7 [1.15-2.51] and less in those with a greater proportion of Galactosylates 0.59 [0.4-0.87], Sialicylates 0.67 [0.45-0.9] and Bisecting-GlcNAc 0.66 [0-45-0.99] (Figure) Conclusions: Glycans, that modulate the IgG function, are a potential prognostic tool for renal function in KT and as a diagnostic support in the identification of patients who develop AMR