Degree of immunoglobulin kappa light chain glycosylation of anti-spike SARS CoV-2 antibodies correlates with COVID-19 severity

Abstract

AbstractGlycosylation of antibodies and the effects this has on inflammatory responses has concentrated predominately on the study of glycosylation moieties found in the Fc region of heavy chains. Light chain glycosylation and their ratios are relatively understudied. Nevertheless, variable glycosylation and ratio of κ and λ light chains have been associated with worse prognosis in myeloma and in tissue deposition – amyloidosis.The κ & λ light chains, of antibodies binding to SARS-CoV2 nucleocapsid and spike protein were analysed, using MALDI-ToF MS, in respect to their intensity, ratios, glycosylation patterns and any pattern changes correlating with COVID-19 severity. The molecular masses and signal intensity of κ and λ glycosylated and non-glycosylated light chains were measured for immunoglobulins isolated from plasma of sero-positive and sero-negative health care workers (HCW), and convalescent patients who had suffered from acute respiratory distress syndrome (ARDS).Overall, there was no significant changes in κ to λ ratio of total IgG (via protein G capture) antibodies between the groups. A non-statistically significant trend towards λ light chains was found in antibodies against SARS CoV-2 Nucleocapsid and Spike proteins. However, detailed analysis of the molecular forms found a significant increase and bias towards un-glycosylated light chains and in particular un-glycosylated κ light chains, in antibodies against SAR-CoV-2 spike protein, from convalescent COVID-ARDS patients.Here we have demonstrated a bias towards un-glycosylated κ chains in anti-spike antibodies in those who suffered from ARDS as a result of SARS-CoV2 infection 3 months after recovery. How this relates to the immunopathology of COVID-19 requires further study.