The Architecture of the IgG Anti-carbohydrate Repertoire in Primary Antibody Deficiencies

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2019 Sep 21

PMID 31537530

Citations 11

Authors

Peter Jandus

Kayluz Frias Boligan

David F Smith

Elisabeth de Graauw

Bodo Grimbacher

Camilla Jandus

Mai M Abdelhafez

Alain Despont

Nicolai Bovin

Dagmar Simon

Robert Rieben

Hans-Uwe Simon

Richard D Cummings

Stephan von Gunten

Affiliations

Soon will be listed here.

Abstract

Immune system failure in primary antibody deficiencies (PADs) has been linked to recurrent infections, autoimmunity, and cancer, yet clinical judgment is often based on the reactivity to a restricted panel of antigens. Previously, we demonstrated that the human repertoire of carbohydrate-specific immunoglobulin G (IgG) exhibits modular organization related to glycan epitope structure. The current study compares the glycan-specific IgG repertoires between different PAD entities. Distinct repertoire profiles with extensive qualitative glycan-recognition defects were observed, which are characterized by the common loss of Galα and GalNAc reactivity and disease-specific recognition of microbial antigens, self-antigens, and tumor-associated carbohydrate antigens. Antibody repertoire analysis may provide a useful tool to elucidate the degree and the clinical implications of immune system failure in individual patients.

Citing Articles

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References

von Gunten S, Smith D, Cummings R, Riedel S, Miescher S, Schaub A . Intravenous immunoglobulin contains a broad repertoire of anticarbohydrate antibodies that is not restricted to the IgG2 subclass. J Allergy Clin Immunol. 2009; 123(6):1268-76.e15. PMC: 2777748. DOI: 10.1016/j.jaci.2009.03.013. View

Schneider C, Smith D, Cummings R, Boligan K, Hamilton R, Bochner B . The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites. Sci Transl Med. 2015; 7(269):269ra1. PMC: 4864610. DOI: 10.1126/scitranslmed.3010524. View

Resnick E, Moshier E, Godbold J, Cunningham-Rundles C . Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2011; 119(7):1650-7. PMC: 3286343. DOI: 10.1182/blood-2011-09-377945. View

de Graauw E, Sitaru C, Horn M, Borradori L, Yousefi S, Simon H . Evidence for a role of eosinophils in blister formation in bullous pemphigoid. Allergy. 2017; 72(7):1105-1113. DOI: 10.1111/all.13131. View

Phelps C, Koike C, Vaught T, Boone J, Wells K, Chen S . Production of alpha 1,3-galactosyltransferase-deficient pigs. Science. 2002; 299(5605):411-4. PMC: 3154759. DOI: 10.1126/science.1078942. View

Galili U . Natural anti-carbohydrate antibodies contributing to evolutionary survival of primates in viral epidemics?. Glycobiology. 2016; 26(11):1140-1150. DOI: 10.1093/glycob/cww088. View

Berbers R, Nierkens S, van Laar J, Bogaert D, Leavis H . Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences. Trends Immunol. 2016; 38(3):206-216. DOI: 10.1016/j.it.2016.11.008. View

Ballow M . Vaccines in the assessment of patients for immune deficiency. J Allergy Clin Immunol. 2012; 130(1):283-4.e5. DOI: 10.1016/j.jaci.2012.04.028. View

Mortaz E, Tabarsi P, Mansouri D, Khosravi A, Garssen J, Velayati A . Cancers Related to Immunodeficiencies: Update and Perspectives. Front Immunol. 2016; 7:365. PMC: 5028721. DOI: 10.3389/fimmu.2016.00365. View

10.

Santos-Silva F, Fonseca A, Caffrey T, Carvalho F, Mesquita P, Reis C . Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism. Glycobiology. 2004; 15(5):511-7. DOI: 10.1093/glycob/cwi027. View

11.

Vajdic C, Mao L, van Leeuwen M, Kirkpatrick P, Grulich A, Riminton S . Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency?. Blood. 2010; 116(8):1228-34. DOI: 10.1182/blood-2010-03-272351. View

12.

Agre P, Bertozzi C, Bissell M, Campbell K, Cummings R, Desai U . Training the next generation of biomedical investigators in glycosciences. J Clin Invest. 2016; 126(2):405-8. PMC: 4731185. DOI: 10.1172/JCI85905. View

13.

Macauley M, Crocker P, Paulson J . Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol. 2014; 14(10):653-66. PMC: 4191907. DOI: 10.1038/nri3737. View

14.

Gelfand E, Ochs H, Shearer W . Controversies in IgG replacement therapy in patients with antibody deficiency diseases. J Allergy Clin Immunol. 2013; 131(4):1001-5. DOI: 10.1016/j.jaci.2013.02.028. View

15.

Durandy A, Kracker S, Fischer A . Primary antibody deficiencies. Nat Rev Immunol. 2013; 13(7):519-33. DOI: 10.1038/nri3466. View

16.

Madi A, Hecht I, Bransburg-Zabary S, Merbl Y, Pick A, Zucker-Toledano M . Organization of the autoantibody repertoire in healthy newborns and adults revealed by system level informatics of antigen microarray data. Proc Natl Acad Sci U S A. 2009; 106(34):14484-9. PMC: 2732819. DOI: 10.1073/pnas.0901528106. View

17.

Grader-Beck T, Boin F, von Gunten S, Smith D, Rosen A, Bochner B . Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease. Ann Rheum Dis. 2011; 70(12):2218-24. PMC: 3409247. DOI: 10.1136/ard.2011.153130. View

18.

Griesemer A, Yamada K, Sykes M . Xenotransplantation: immunological hurdles and progress toward tolerance. Immunol Rev. 2014; 258(1):241-58. PMC: 4023346. DOI: 10.1111/imr.12152. View

19.

Haas Q, Boligan K, Jandus C, Schneider C, Simillion C, Stanczak M . Siglec-9 Regulates an Effector Memory CD8 T-cell Subset That Congregates in the Melanoma Tumor Microenvironment. Cancer Immunol Res. 2019; 7(5):707-718. DOI: 10.1158/2326-6066.CIR-18-0505. View

20.

Al-Herz W, Bousfiha A, Casanova J, Chapel H, Conley M, Cunningham-Rundles C . Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2012; 2:54. PMC: 3342372. DOI: 10.3389/fimmu.2011.00054. View