N-glycosylation of immunoglobulin A in children and adults with type 1 diabetes mellitus.

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.

IgG glycans in health and disease: Prediction, intervention, prognosis, and therapy.

Immunoglobulin (IgG) glycosylation is a complex enzymatically controlled process, essential for the structure and function of IgG. IgG glycome is relatively stable in the state of homeostasis, yet its alterations have been associated with aging, pollution and toxic exposure, as well as various diseases, including autoimmune and inflammatory diseases, cardiometabolic diseases, infectious diseases and cancer. IgG is also an effector molecule directly involved in the inflammation processes included in the pathogenesis of many diseases. Numerous recently published studies support the idea that IgG N-glycosylation fine-tunes the immune response and plays a significant role in chronic inflammation. This makes it a promising novel biomarker of biological age, and a prognostic, diagnostic and treatment evaluation tool. Here we provide an overview of the current state of knowledge regarding the IgG glycosylation in health and disease, and its potential applications in pro-active prevention and monitoring of various health interventions.

Role of substituents in the Hofmann-Löffler-Freytag reaction. A quantum-chemical case study on nicotine synthesis.

The Hofmann-Löffler-Freytag (HLF) reaction can be successfully used to synthesize saturated heterocyclic nitrogen-containing nature-derived pharmaceuticals such as nicotine and its derivatives. In this study the rate-determining hydrogen atom transfer (HAT) step in nicotine synthesis has been analyzed using quantum chemical methods. Through quantification of substituent effects in the HAT step of the reaction on both nitrogen and carbon atoms, optimized synthetic strategies are outlined for the racemic as well as the stereoselective synthesis of nicotine. This latter process can be achieved using common nitrogen protecting groups, such as Ac, TFAc, and Boc. The said protecting groups show superior nitrogen radical activation as compared to the commonly used Tosyl group. Computational results indicate that the 1,5-HAT step is in this case likely to work even for the reaction with primary unactivated carbon centers.