Development of Antibodies to Human Leukocyte Antigen Precedes Development of Antibodies to Major Histocompatibility Class I-related Chain A and Are Significantly Associated with Development of Chronic Rejection After Human Lung Transplantation

Overview

Journal Hum Immunol

Specialty Allergy & Immunology

Date 2010 Mar 10

PMID 20211214

Citations 23

Authors

Nataraju Angaswamy

Deepti Saini

Sabarinathan Ramachandran

Dilip S Nath

Donna Phelan

Ramsey Hachem

Elbert Trulock

G Alexander Patterson

T Mohanakumar

Affiliations

Soon will be listed here.

Abstract

The development of antibodies (Abs) to major histocompatibility (MHC) class I-related chain A (MICA) and human leukocyte antigen (HLA) and their role in the immunopathogenesis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) after human lung transplantation (LTx) was analyzed. Sera from 80 LTx recipients were analyzed for anti-MICA and anti-HLA Abs using Luminex and flow PRA (panel reactive assay). Development of Abs either to MICA alone or MICA and HLA together significantly correlated (p < 0.01) with development of BOS. Kinetic analysis in the post-LTx period revealed that development of anti-HLA Abs (7.6 +/- 4.7 months) preceded the development of anti-MICA Abs (10.0 +/- 3.5 months). Abs to MICA alleles (*001 and *009) developed approximately 6 months after LTx and peak titers were present at the time of clinical diagnosis of BOS (16.3 +/- 2.7 months). The development of Abs to both MICA and HLA was strongly associated with the development of BOS thereby suggesting a synergistic effect. Furthermore, immune response to mismatched HLA can lead to development of Abs to other MHC related antigens expressed on the airway epithelial cells. Cumulatively, these immune responses contribute to the pathogenesis of chronic rejection following human LTx.

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References

Kaczmarek I, Deutsch M, Kauke T, Beiras-Fernandez A, Schmoeckel M, Vicol C . Donor-specific HLA alloantibodies: long-term impact on cardiac allograft vasculopathy and mortality after heart transplant. Exp Clin Transplant. 2008; 6(3):229-35. View

Iwata T, Philipovskiy A, Fisher A, Presson Jr R, Chiyo M, Lee J . Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction. J Immunol. 2008; 181(8):5738-47. PMC: 2997998. DOI: 10.4049/jimmunol.181.8.5738. View

Kauke T, Kaczmarek I, Dick A, Schmoeckel M, Deutsch M, Beiras-Fernandez A . Anti-MICA antibodies are related to adverse outcome in heart transplant recipients. J Heart Lung Transplant. 2009; 28(4):305-11. DOI: 10.1016/j.healun.2009.01.003. View

Aquino-Galvez A, Perez-Rodriguez M, Camarena A, Falfan-Valencia R, Ruiz V, Montano M . MICA polymorphisms and decreased expression of the MICA receptor NKG2D contribute to idiopathic pulmonary fibrosis susceptibility. Hum Genet. 2009; 125(5-6):639-48. DOI: 10.1007/s00439-009-0666-1. View

Ho E, Vlad G, Colovai A, Rodica Vasilescu E, Schwartz J, Sondermeijer H . Alloantibodies in heart transplantation. Hum Immunol. 2009; 70(10):825-9. DOI: 10.1016/j.humimm.2009.06.015. View

Montgomery R, Hardy M, Jordan S, Racusen L, Ratner L, Tyan D . Consensus opinion from the antibody working group on the diagnosis, reporting, and risk assessment for antibody-mediated rejection and desensitization protocols. Transplantation. 2004; 78(2):181-5. DOI: 10.1097/01.tp.0000129256.84027.d6. View

Cooper J, Billingham M, Egan T, Hertz M, Higenbottam T, Lynch J . A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 1993; 12(5):713-6. View

Schulman L, Ho E, Reed E, McGregor C, Smith C, Rose E . Immunologic monitoring in lung allograft recipients. Transplantation. 1996; 61(2):252-7. DOI: 10.1097/00007890-199601270-00016. View

Reed E, Hong B, Ho E, Harris P, Weinberger J, Suciu-Foca N . Monitoring of soluble HLA alloantigens and anti-HLA antibodies identifies heart allograft recipients at risk of transplant-associated coronary artery disease. Transplantation. 1996; 61(4):566-72. DOI: 10.1097/00007890-199602270-00009. View

10.

Yousem S, Berry G, Cagle P, Chamberlain D, Husain A, Hruban R . Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group. J Heart Lung Transplant. 1996; 15(1 Pt 1):1-15. View

11.

Bian H, Harris P, Mulder A, Reed E . Anti-HLA antibody ligation to HLA class I molecules expressed by endothelial cells stimulates tyrosine phosphorylation, inositol phosphate generation, and proliferation. Hum Immunol. 1997; 53(1):90-7. DOI: 10.1016/S0198-8859(96)00272-8. View

12.

Kroshus T, Kshettry V, Savik K, John R, Hertz M, Bolman 3rd R . Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation. J Thorac Cardiovasc Surg. 1997; 114(2):195-202. DOI: 10.1016/S0022-5223(97)70144-2. View

13.

Sundaresan S, Mohanakumar T, Smith M, Trulock E, Lynch J, Phelan D . HLA-A locus mismatches and development of antibodies to HLA after lung transplantation correlate with the development of bronchiolitis obliterans syndrome. Transplantation. 1998; 65(5):648-53. DOI: 10.1097/00007890-199803150-00008. View

14.

Boehler A, Kesten S, Weder W, Speich R . Bronchiolitis obliterans after lung transplantation: a review. Chest. 1998; 114(5):1411-26. DOI: 10.1378/chest.114.5.1411. View

15.

Jaramillo A, Smith M, Phelan D, Sundaresan S, Trulock E, Lynch J . Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation. Transplantation. 1999; 67(8):1155-61. DOI: 10.1097/00007890-199904270-00012. View

16.

Jaramillo A, Fernandez F, Kuo E, Trulock E, Patterson G, Mohanakumar T . Immune mechanisms in the pathogenesis of bronchiolitis obliterans syndrome after lung transplantation. Pediatr Transplant. 2005; 9(1):84-93. DOI: 10.1111/j.1399-3046.2004.00270.x. View

17.

Rees M, Downing J, Darke C . A typing system for the major histocompatibility complex class I chain related genes A and B using polymerase chain reaction with sequence-specific primers. Genet Test. 2005; 9(2):93-110. DOI: 10.1089/gte.2005.9.93. View

18.

Hourmant M, Cesbron-Gautier A, Terasaki P, Mizutani K, Moreau A, Meurette A . Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation. J Am Soc Nephrol. 2005; 16(9):2804-12. DOI: 10.1681/ASN.2004121130. View

19.

Terasaki P, Cai J . Humoral theory of transplantation: further evidence. Curr Opin Immunol. 2005; 17(5):541-5. DOI: 10.1016/j.coi.2005.07.018. View

20.

Reed E, Demetris A, Hammond E, Itescu S, Kobashigawa J, Reinsmoen N . Acute antibody-mediated rejection of cardiac transplants. J Heart Lung Transplant. 2006; 25(2):153-9. DOI: 10.1016/j.healun.2005.09.003. View