Ana Cindrić, Dionysis Nikolopoulos, Natalia Sherina, Frano Vučković, Farah Tamirou, Anne-Marie Patenaude, Maja Pučić-Baković, Barbara Radovani Trbojević, Frédéric A Houssiau, Gordan Lauc, Ioannis Parodis
Significant alterations in IgG glycosylation were observed between the two time points. In total IgG, decreased sialylation and increased monogalactosylated structures were prominent. Fragment-specific analyses revealed divergent dynamics: the Fc region showed increased asialylation and a higher proportion of bisecting GlcNAc-containing glycans, consistent with a pro-inflammatory effector profile, while the Fab region exhibited increased digalactosylated glycans and decreased fucosylation, a pattern not mirrored in the Fc region or total IgG glycome.
INTRODUCTION: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) characterized by immune dysregulation and kidney inflammation. Alterations in immunoglobulin G (IgG) glycosylation are known to influence immune responses and have been implicated in autoimmune diseases, including SLE and LN. This study aimed to investigate longitudinal changes in IgG glycosylation in patients with active LN, from before treatment to one year after immunosuppressive therapy initiation.
METHODS: Serum samples were collected from 17 patients with LN at two time points, i.e., at active LN, prior to treatment initiation (baseline), and after 12 months of therapy. IgG was purified and subjected to detailed glycosylation analysis (total and fragment-specific) by capillary gel electrophoresis (CGE). Changes in glycosylation patterns between the two time points were assessed using linear mixed effects and regression models.
RESULTS: Significant alterations in IgG glycosylation were observed between the two time points. In total IgG, decreased sialylation and increased monogalactosylated structures were prominent. Fragment-specific analyses revealed divergent dynamics: the Fc region showed increased asialylation and a higher proportion of bisecting GlcNAc-containing glycans, consistent with a pro-inflammatory effector profile, while the Fab region exhibited increased digalactosylated glycans and decreased fucosylation, a pattern not mirrored in the Fc region or total IgG glycome.
DISCUSSION: These findings indicate pro-inflammatory longitudinal shifts in IgG glycosylation during the transition of LN from an active to a treated disease state. The study underscores the relevance of IgG glycosylation in LN pathophysiology and suggests that IgG glycosylation patterns change following immunosuppressive therapy for active LN, potentially reflecting ongoing disease-related immune processes despite improvement in conventional clinical parameters.