Protein glycosylation is an important co- and post-translational modification that is critical for many protein functions and biological processes. Glycan biosynthesis is a non-template driven cellular process, which gives rise to glycan structural heterogeneity. Glycome modulations coincide with the development of a number of diseases including cancer as well as inflammatory diseases. Therefore, such alterations are of diagnostic relevance to monitor remission and relapse. Immunoglobulin G (IgG), the most abundant serum glycoprotein, plays a vital role in the humoral immune response by recognizing and eliminating harmful antigens as well as pathogens. N-Glycosylation of the constant IgG Fc portion is altered during pathological or changed physiological conditions that modulates antibody effector functions. In a first article, the human N-glycome was investigated in detail by CE-LIF. Glycome modulations of serum proteins in the course of diseases had so far only been identified for the 12 most abundant glycan isomers. Reference glycoproteins as well as an exoglycosidase digestion array were used to identify linkage and positional isomers of desialylated N-glycans from human serum by CE-LIF. It was possible to assign and quantify 34 N-glycan isomers in the serum of epithelial ovarian cancer (EOC) patients. It could be confirmed that the levels of diantennary structures and of high-mannose 5 were significantly lower in patients with EOC than in healthy controls. The hallmark of cancer modulation, namely elevated branching as well as increased antennary fucosylation, was also detected in EOC patients. In addition, low abundant but biologically significant core-fucosylated tri- and tetraantennary N-glycan structures were identified, which resulted in an improvement of N-glycome analysis when compared with earlier studies. This could also lead to novel glycan biomarkers for EOC. The second aim of this work was the optimization of N-glycan analysis using capillary electrophoresis coupled with laser-induced fluorescence (CE-LIF). CE-LIF is currently one of the most popular methods for separating IgG N-glycan isomers. To date, the measurement of sialylated N-glycans using this instrument was challenging. Due to their negative charge sialic acids have short migration times, which results in peak co-migration and reduced resolution. A protocol was developed in this work to enhance N-glycan resolution by methylating the negative charge of carboxylic groups of sialic acids. The migration times of sialylated N-glycans are then delayed, which results in improved resolution and better quantification of N-glycan isomers by CE-LIF. To evaluate this new method, Fc-glycosylation of IgG isolated from EOC patients and healthy controls was analyzed using the conventional and the methylation method. With both methods, an increase of agalactosylated structures was measured. However, due to the superior resolution of the methylation method, an increase of an afucosylated truncated structure could be also detected. IgG hypogalactosylation has been widely recognized for its association with inflammatory disease activity in rheumatoid arthritis (RA) and its dependence on activation of humoral immunity. It was therefore examined in a third article whether the correlation between IgG agalactosylation and inflammation depends on the presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), or HLA-DRB1 shared epitope (SE). Furthermore, it was investigated whether IgG glycosylation is related to inflammation in axial spondyloarthritis (axSpA). IgG-Fc N-glycosylation analysis was carried out using CE-LIF to compare the serum of RA patients, axSpA patients, and healthy controls. Differences in IgG-Fc galactosylation were assessed in relation to C-reactive protein (CRP) concentrations. The relation between IgG hypogalactosylation and disease activity markers (CRP, erythrocyte sedimentation rate, DAS28) was studied in RA stratified by HLA-DRB1 SE, ACPA, or RF. Aberrant galactosylation of IgG was found to be strongly dependent on inflammatory activity in RA, but was missing in non-humoral autoimmune processes like axSpA. In RA, IgG galactosylation was present in SE-negative/ACPA-negative individuals and was comparable to galacosylation levels of axSpA patients and healthy controls, indicating humoral activation with a different specificity in this subset. Assessing the correlation between IgG hypogalactosylation and disease activity markers, a significant heterogeneity between strata defined by SE as well as RF but no difference between both ACPA-strata was found. This finding sheds novel light on the relation between SE, ACPA and RF in RA.