N-glycosylation of immunoglobulin A in children and adults with type 1 diabetes mellitus
Matej Nemčić,
Sofia Shkunnikova,
Domagoj Kifer,
Branimir Plavša,
Marijana Vučić Lovrenčić,
Grant Morahan,
Lea Duvnjak,
Flemming Pociot,
Olga Gornik
Affiliations
Matej Nemčić
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb, Croatia
Sofia Shkunnikova
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb, Croatia
Domagoj Kifer
Department of Biophysics, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb, Croatia
Branimir Plavša
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb, Croatia
Marijana Vučić Lovrenčić
Department of Laboratory Medicine, Merkur University Hospital, Zajčeva 19, Zagreb, Croatia
Grant Morahan
Centre for Diabetes Research, The Harry Perkins Institute for Medical Research, 6 Verdun St, Nedlands, WA, Australia; Australian Centre for Accelerating Diabetes Innovations, University of Melbourne, Parkville, Victoria, 3010, VIC, Australia
Lea Duvnjak
Department of Endocrinology, Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Dugi dol 4A, Zagreb, Croatia
Flemming Pociot
Department of Clinical Research, Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen, Denmark
Olga Gornik
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb, Croatia; Corresponding author. Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000, Zagreb, Croatia.
Aims: To identify N-glycan structures on immunoglobulin A related to type 1 diabetes mellitus among children at the disease onset and adults with type 1 diabetes mellitus. Methods: Human polyclonal IgA N-glycans were profiled using hydrophilic interaction ultra performance liquid chromatography in two cohorts. The first cohort consisted of 62 children at the onset of type 1 diabetes mellitus and 86 of their healthy siblings. The second cohort contained 84 adults with the disease and 84 controls. Associations between N-glycans and type 1 diabetes mellitus were tested using linear mixed model for the paediatric cohort, or general linear model for the adult cohort. False discovery rate was controlled by Benjamini-Hochberg method modified by Li and Ji. Results: In children, an increase in a single oligomannose N-glycan was associated with type 1 diabetes mellitus (B = 0.529, p = 0.0067). N-glycome of the adults displayed increased branching (B = 0.466, p = 0.0052), trigalactosylation (B = 0.466, p = 0.0052), trisialylation (B = 0.629, p < 0.001), and mannosylation (B = 0.604, p < 0.001). The strongest association with the disease was a decrease in immunoglobulin A core fucosylation (B = −0.900, p < 0.001). Conclusions: Changes in immunoglobulin N-glycosylation patterns in type 1 diabetes point to disruptions in immunoglobulin A catabolism and dysregulated inflammatory capabilities of the antibody, potentially impacting immune responses and inflammation.
