In from the cold: M-protein light chain glycosylation is positively associated with cold agglutinin titer levels.

Publisher: American Association Of Blood Banks Country of Publication: United States NLM ID: 0417360 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-2995 (Electronic) Linking ISSN: 00411132 NLM ISO Abbreviation: Transfusion Subsets: MEDLINE

Original Publication: Arlington, Va. : American Association Of Blood Banks

Anemia, Hemolytic, Autoimmune/*immunology ; Complement System Proteins/*immunology ; Immunoglobulin Light-chain Amyloidosis/*metabolism ; Myeloma Proteins/*metabolism; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/immunology ; Complement Fixation Tests/statistics & numerical data ; Coombs Test/methods ; Cross-Sectional Studies ; Cryoglobulins/analysis ; Cryoglobulins/immunology ; Female ; Glycosylation ; Hemolysis/immunology ; Humans ; Immunoglobulin Light-chain Amyloidosis/immunology ; Immunoglobulin kappa-Chains/metabolism ; Male ; Mass Spectrometry/methods ; Middle Aged

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.
(© 2021 AABB.)

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Keywords: AIHA/drug-induced IHA; hematology - red cells; immunohematology (RBC serology, blood groups)

0 (Antibodies, Monoclonal)
0 (Cryoglobulins)
0 (Immunoglobulin kappa-Chains)
0 (Myeloma Proteins)
0 (cold agglutinins)
0 (multiple myeloma M-proteins)
9007-36-7 (Complement System Proteins)

Date Created: 20210127 Date Completed: 20210719 Latest Revision: 20210719

20221213

10.1111/trf.16279

33502021