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Immunoglobulin A Glycosylation and Its Role in Disease

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Antibody Glycosylation

Part of the book series: Experientia Supplementum ((EXS,volume 112))

Abstract

Human IgA is comprised of two subclasses, IgA1 and IgA2. Monomeric IgA (mIgA), polymeric IgA (pIgA), and secretory IgA (SIgA) are the main molecular forms of IgA. The production of IgA rivals all other immunoglobulin isotypes. The large quantities of IgA reflect the fundamental roles it plays in immune defense, protecting vulnerable mucosal surfaces against invading pathogens. SIgA dominates mucosal surfaces, whereas IgA in circulation is predominately monomeric. All forms of IgA are glycosylated, and the glycans significantly influence its various roles, including antigen binding and the antibody effector functions, mediated by the Fab and Fc portions, respectively. In contrast to its protective role, the aberrant glycosylation of IgA1 has been implicated in the pathogenesis of autoimmune diseases, such as IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). Furthermore, detailed characterization of IgA glycosylation, including its diverse range of heterogeneity, is of emerging interest. We provide an overview of the glycosylation observed for each subclass and molecular form of IgA as well as the range of heterogeneity for each site of glycosylation. In many ways, the role of IgA glycosylation is in its early stages of being elucidated. This chapter provides an overview of the current knowledge and research directions.

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Abbreviations

C1GalT1:

Core 1 β1,3-galactosyltransferase

dIgA:

Dimeric IgA

EBV:

Epstein–Barr virus

ECD:

Electron capture dissociation

ETD:

Electron transfer dissociation

FcRL4:

Fc receptor-like 4

Gal:

Galactose

GalNAc:

N-acetylgalactosamine

GalNAc-T:

GalNAc-transferase

Gd-IgA1:

Galactose-deficient IgA1

HC:

Heavy chain

HR:

Hinge region

Ig:

Immunoglobulin

IgAN:

IgA nephropathy

IgAV:

IgA vasculitis

IgAVN:

IgA vasculitis with nephritis

LC:

Light chain

MBL:

Mannose-binding lectin

mIgA:

Monomeric IgA

MS:

Mass spectrometry

pIgA:

Polymeric IgA

RA:

Rheumatoid arthritis

SA:

Sialic acid

SC:

Secretory component

SIgA:

Secretory IgA

SLE:

Systemic lupus erythematosus

TG2:

Transglutaminase 2

V:

Variable

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Acknowledgments

The authors express their appreciation to the colleagues and collaborators as well as to all volunteers participating in the cited studies. The authors apologize to their colleagues in the field whose work is not adequately discussed or cited in this review due to the space limitations.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    Alyssa L. Hansen & Matthew B. Renfrow

  2. Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Colin Reily

  3. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Jan Novak

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  1. Alyssa L. Hansen
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  2. Colin Reily
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  3. Jan Novak
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  4. Matthew B. Renfrow
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Corresponding authors

Correspondence to Jan Novak or Matthew B. Renfrow .

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Editors and Affiliations

  1. Glycoscience Research Laboratory, Genos Ltd., Zagreb, Croatia

    Marija Pezer

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Funding

The authors of this study were supported in part by NIH grants AR069516, DK106341, CD122194, GM098539, DK078244, and DK082753 and by a gift from the IGA Nephropathy Foundation of America.

Conflict of Interest

MBR and JN are co-founders and co-owners of and consultants for Reliant Glycosciences, LLC. MBR and JN are co-inventors on US patent application 14/318,082 (assigned to UAB Research Foundation). ALH and CR declare no conflict of interest.

Ethical Approval

Not applicable, as this is a review article and, thus, there are no human subjects recruited for this study or any animals used.

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Not applicable, as this is a review article and, thus, there are no human subjects recruited for this study.

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Hansen, A.L., Reily, C., Novak, J., Renfrow, M.B. (2021). Immunoglobulin A Glycosylation and Its Role in Disease. In: Pezer, M. (eds) Antibody Glycosylation. Experientia Supplementum, vol 112. Springer, Cham. https://doi.org/10.1007/978-3-030-76912-3_14

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