Antibody Subclass Repertoire and Graft Outcome Following Solid Organ Transplantation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2016 Nov 9

PMID 27822209

Citations 18

Authors

Nicole M Valenzuela

Michelle J Hickey

Elaine F Reed

Affiliations

Soon will be listed here.

Abstract

Long-term outcomes in solid organ transplantation are constrained by the development of donor-specific alloantibodies (DSA) against human leukocyte antigen (HLA) and other targets, which elicit antibody-mediated rejection (ABMR). However, antibody-mediated graft injury represents a broad continuum, from extensive complement activation and tissue damage compromising the function of the transplanted organ, to histological manifestations of endothelial cell injury and mononuclear cell infiltration but without concurrent allograft dysfunction. In addition, while transplant recipients with DSA as a whole fare worse than those without, a substantial minority of patients with DSA do not experience poorer graft outcome. Taken together, these observations suggest that not all DSA are equally pathogenic. Antibody effector functions are controlled by a number of factors, including antibody concentration, antigen availability, and antibody isotype/subclass. Antibody isotype is specified by many integrated signals, including the antigen itself as well as from antigen-presenting cells or helper T cells. To date, a number of studies have described the repertoire of IgG subclasses directed against HLA in pretransplant patients and evaluated the clinical impact of different DSA IgG subclasses on allograft outcome. This review will summarize what is known about the repertoire of antibodies to HLA and non-HLA targets in transplantation, focusing on the distribution of IgG subclasses, as well as the general biology, etiology, and mechanisms of injury of different humoral factors.

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References

Heidt S, Roelen D, Eijsink C, Eikmans M, van Kooten C, Claas F . Calcineurin inhibitors affect B cell antibody responses indirectly by interfering with T cell help. Clin Exp Immunol. 2009; 159(2):199-207. PMC: 2810388. DOI: 10.1111/j.1365-2249.2009.04051.x. View

Wiebe C, Nevins T, Robiner W, Thomas W, Matas A, Nickerson P . The Synergistic Effect of Class II HLA Epitope-Mismatch and Nonadherence on Acute Rejection and Graft Survival. Am J Transplant. 2015; 15(8):2197-202. DOI: 10.1111/ajt.13341. View

Pene J, Gauchat J, Lecart S, Drouet E, Guglielmi P, Boulay V . Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells. J Immunol. 2004; 172(9):5154-7. DOI: 10.4049/jimmunol.172.9.5154. View

Medina Pestana J, Grinyo J, Vanrenterghem Y, Becker T, Campistol J, Florman S . Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys. Am J Transplant. 2012; 12(3):630-9. DOI: 10.1111/j.1600-6143.2011.03914.x. View

Cooper L, Robertson D, Granzow R, Greenspan N . Variable domain-identical antibodies exhibit IgG subclass-related differences in affinity and kinetic constants as determined by surface plasmon resonance. Mol Immunol. 1994; 31(8):577-84. DOI: 10.1016/0161-5890(94)90165-1. View

Migot-Nabias F, Lokossou A, Vigan-Womas I, Guitard E, Guillotte M, Noukpo J . Combined effects of Gm or Km immunoglobulin allotypes and age on antibody responses to Plasmodium falciparum VarO rosetting variant in Benin. Microbes Infect. 2011; 13(8-9):771-5. DOI: 10.1016/j.micinf.2011.04.001. View

Haas M, Sis B, Racusen L, Solez K, Glotz D, Colvin R . Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014; 14(2):272-83. DOI: 10.1111/ajt.12590. View

Hidalgo L, Sellares J, Sis B, Mengel M, Chang J, Halloran P . Interpreting NK cell transcripts versus T cell transcripts in renal transplant biopsies. Am J Transplant. 2012; 12(5):1180-91. DOI: 10.1111/j.1600-6143.2011.03970.x. View

Crespo M, Torio A, Mas V, Redondo D, Perez-Saez M, Mir M . Clinical relevance of pretransplant anti-HLA donor-specific antibodies: does C1q-fixation matter?. Transpl Immunol. 2013; 29(1-4):28-33. DOI: 10.1016/j.trim.2013.07.002. View

10.

Reinsmoen N, Lai C, Heidecke H, Haas M, Cao K, Ong G . Anti-angiotensin type 1 receptor antibodies associated with antibody mediated rejection in donor HLA antibody negative patients. Transplantation. 2010; 90(12):1473-7. DOI: 10.1097/TP.0b013e3181fd97f1. View

11.

Nimmerjahn F, Ravetch J . Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science. 2005; 310(5753):1510-2. DOI: 10.1126/science.1118948. View

12.

Regan J, Monteiro F, Speiser D, Kalil J, Pouletty P, Buelow R . Pretransplant rejection risk assessment through enzyme-linked immunosorbent assay analysis of anti-HLA class I antibodies. Am J Kidney Dis. 1996; 28(1):92-8. DOI: 10.1016/s0272-6386(96)90136-5. View

13.

Adebiyi O, Gralla J, Klem P, Freed B, Davis S, Wiseman A . Clinical Significance of Pretransplant Donor-Specific Antibodies in the Setting of Negative Cell-Based Flow Cytometry Crossmatching in Kidney Transplant Recipients. Am J Transplant. 2016; 16(12):3458-3467. DOI: 10.1111/ajt.13848. View

14.

Morton A, Bell E, Bolton E, MARSHALL H, Roadknight C, McDonagh M . CD4+ T cell-mediated rejection of major histocompatibility complex class I-disparate grafts: a role for alloantibody. Eur J Immunol. 1993; 23(9):2078-84. DOI: 10.1002/eji.1830230906. View

15.

Loupy A, Lefaucheur C, Vernerey D, Prugger C, Duong van Huyen J, Mooney N . Complement-binding anti-HLA antibodies and kidney-allograft survival. N Engl J Med. 2013; 369(13):1215-26. DOI: 10.1056/NEJMoa1302506. View

16.

Wahrmann M, Hlavin G, Fischer G, Marinova L, Schwaiger E, Horl W . Modified solid-phase alloantibody detection for improved crossmatch prediction. Hum Immunol. 2012; 74(1):32-40. DOI: 10.1016/j.humimm.2012.10.012. View

17.

Aalberse R, Stapel S, Schuurman J, Rispens T . Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009; 39(4):469-77. DOI: 10.1111/j.1365-2222.2009.03207.x. View

18.

Devey M, Bird P, Amlot P . Antibodies of different human IgG subclasses show distinct patterns of affinity maturation after immunization with keyhole limpet haemocyanin. Immunology. 1990; 70(2):168-74. PMC: 1384188. View

19.

Borriello F, Sethna M, Boyd S, Schweitzer A, Tivol E, Jacoby D . B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity. 1997; 6(3):303-13. DOI: 10.1016/s1074-7613(00)80333-7. View

20.

Chin C, Chen G, Sequeria F, Berry G, Siehr S, Bernstein D . Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients. J Heart Lung Transplant. 2010; 30(2):158-63. DOI: 10.1016/j.healun.2010.08.020. View