Capillary electrophoresis analysis of N‐glycosylation changes of serum paraproteins in multiple myeloma

Abstract

Multiple myeloma (MM) is an immedicable malignancy of the human plasma cells producing abnormal antibodies (also referred to as paraproteins) leading to kidney problems and hyperviscosity syndrome. In this paper, we report on the N-glycosylation analysis of paraproteins from total human serum as well as the fragment crystallizable region (F ) and fragment antigen binding (F ) κ/λ light chain fractions of papain digested immunoglobulins from multiple myeloma patients. CE-LIF detection was used for the analysis of the N-glycans after endoglycosidase (PNGase F) mediated sugar release and fluorophore labeling (APTS). While characteristic N-glycosylation pattern differences were found between normal control and untreated, treated and remission stage multiple myeloma patient samples at the global serum level, less distinctive changes were observed at the immunoglobulin level. Principal component analysis adequately differentiated the four groups (control and three patient groups) on the basis of total serum N-glycosylation analysis. 12 N-glycan features showed statistically significant differences (p <0.05) among various stages of the disease in comparison to the control at the serum level, while only six features were identified with similar significance at the immunoglobulin level, including the analysis of the partitioned F fragment as well as the F κ and F λ chains.

Hydrophilic interaction liquid chromatography in the separation of glycopeptides and their isomers

“…Moreover, alteration of glycosylation has been found to be related to several diseases [1–4]. Despite the recent innovations of bioanalytical techniques [5], analysis of glycoproteins is still a challenge mainly because of their micro- and macro- heterogeneity [6].…”

Protein és glikán biomarkerek szerepe a krónikus obstruktív tüdőbetegség diagnosztikájában

“…A glikozilációs állapot a sejtfelszíni és plazmafehérjék számos tulajdonságát (élettartam, receptorfunkció) befolyásolhatja, illetve az adott betegségre jellemző, szabálytalan glikozilációs mintázat megjelenéséhez vezethet. A glikozilációs mintázatban bekövetkező jellegzetes változások használhatók adott betegségek diagnosztizálása során [33]. A COPD-ben észlelt gli kozilációs módosulások egyes receptormolekulák működésében változást okozhatnak.…”

The effect of simulated space radiation on the N‐glycosylation of human immunoglobulin G1

“…After long‐term strongly ionizing radiation exposure, inflammatory proteins like cytokines are induced and specific immunoglobulin levels (IgG and IgM) are bouncing in the human body . Immunoglobulin represent ∼25% of serum proteins, thus their glycosylation changes can be readily followed and therefore used as a candidate biomarkers for various diseases. Astronauts during long duration (deep space) missions leave the protecting magnetic field of Earth and exposed to the harming ionizing radiation of GCRs and SPEs for the duration of their journey, possibly up to years.…”