logo SBA

ETD

Digital archive of theses discussed at the University of Pisa

 

Thesis etd-09102021-174317


Thesis type
Tesi di dottorato di ricerca
Author
CAPECCHI, RICCARDO
URN
etd-09102021-174317
Thesis title
IgG glycosylation in Primary Antibody Deficiencies
Academic discipline
MED/09
Course of study
SCIENZE CLINICHE E TRASLAZIONALI
Supervisors
tutor Prof.ssa Migliorini, Paola
Keywords
  • Common Variable Immunodeficiency
  • CVID
  • glycosylation
  • IgG
  • lectin
  • Primary Antibody Deficency
Graduation session start date
13/09/2021
Availability
Withheld
Release date
13/09/2024
Summary
Immunoglobulin glycosylation has a strong impact on antibody function, by modifying protein conformation and IgG binding for Fc-Receptors and complement. To elucidate the role of IgG glycosylation in Primary Antibody Deficiencies (PAD), we developed a lectin-based ELISA assay in to estimate the proportion of different glycidic patterns on circulating IgG complex. METHODS: Seven naïve Common Variable Immunodeficiency (CVID) patients were recruited. Controls include eleven patients with IgG subclasses deficiency (IGSCD), thirty-one subjects with Unclassified Antibody Deficiency (uAD) and 35 healthy subjects. Fifty-one patients already on substitution therapy were also examined (14 CVID, 9 IGSCD and 29 uAD). Six Ig product were evaluated. Plates were coated with Protein A to evaluate circulating IgG complex, or Tetanus toxoid(TT) or EBNA peptide(EBNA) to explore antigen-specific Ig glycosylation. RESULTS: CVID patients presents a significantly reduced binding of each lectin in comparison with NHS. Commercial immunoglobulin preparations present very low binding of lectins in comparison with patients and control groups. Lectin binding levels are independent by serum IgG and correlate with soluble BCMA, a plasma cell activity marker. Ig SNA binding, associated to sialylation, is lower in patients with reduced number of Switched memory B cells. Symptomatic patients present significantly lower binding of AAL in comparison with paucisymptomatic patients and NHS, suggesting a major proportion of afucosylated antibodies. Specific differences are seen in anti-TT antibodies between healthy controls and PAD in terms of JAC and SNA binding, suggesting an independent and antigen-specific regulatory mechanism of glycan expression.
File