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In from the cold: M-protein light chain glycosylation is positively associated with cold agglutinin titer levels
- Source :
- TransfusionREFERENCES. 61(4)
- Publication Year :
- 2020
-
Abstract
- Background Primary cold agglutinin disease (CAD) is a monoclonal antibody (M-protein) and complement-mediated chronic hemolytic disease process. Antibody glycosylation can play a role in both antibody half-life and complement fixation. Recently, M-protein light chain (LC) glycosylation has been shown to be associated with AL amyloidosis. We hypothesized that M-protein LC glycosylation is also associated with cold agglutinin (CA) titers and CA-mediated hemolysis. Study design and methods A cross-sectional study of patients undergoing CA titer evaluation underwent mass spectrometric analysis for M-proteins and M-protein LC glycosylation. A subset of serum samples also underwent evaluation for the ability to trigger cold hemolysis in vitro. M-protein and M-protein LC glycosylation rates were compared across CA titer groups, clinical diagnosis, direct antiglobulin testing (DAT) results, and cold in vitro hemolysis rates. Results Both M-protein and M-protein LC glycosylation rates significantly differed across CA titer groups with the highest rates in those with elevated CA titers. M-protein LC glycosylation occurred almost exclusively on IgM kappa M-proteins and was significantly associated with positive DAT results and a clinical diagnosis of CAD. Cold in vitro hemolysis was demonstrated in two patients who both had a CA titer of more than 512 but there was no significant association with CA titer group or M-protein LC glycosylation status. Conclusion M-protein LC glycosylation is significantly associated with higher CA titer levels. Given the role that antibody glycosylation can play in antibody half-life and complement fixation, further studies are needed to clarify the effects of LC glycosylation within the context of CAD.
- Subjects :
- Adult
Male
Glycosylation
Cold agglutinin disease
Immunology
Context (language use)
030204 cardiovascular system & hematology
Hemolysis
Mass Spectrometry
03 medical and health sciences
chemistry.chemical_compound
Immunoglobulin kappa-Chains
0302 clinical medicine
medicine
Immunology and Allergy
Humans
Immunoglobulin Light-chain Amyloidosis
Cryoglobulins
Aged
Aged, 80 and over
biology
Complement Fixation Tests
Antibodies, Monoclonal
Hematology
Complement System Proteins
Middle Aged
medicine.disease
Complement fixation test
Molecular biology
Cold Agglutinin
carbohydrates (lipids)
Titer
Coombs Test
Cross-Sectional Studies
Myeloma Proteins
chemistry
biology.protein
lipids (amino acids, peptides, and proteins)
Female
Anemia, Hemolytic, Autoimmune
Antibody
030215 immunology
Subjects
Details
- ISSN :
- 15372995
- Volume :
- 61
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- TransfusionREFERENCES
- Accession number :
- edsair.doi.dedup.....ccde7c7f9a89de6443a1bae717a524ff