1887

Chapter 16 : Complement in Transplant Rejection

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Complement in Transplant Rejection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815905/9781555813642_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555815905/9781555813642_Chap16-2.gif

Abstract:

This chapter examines the advantages and disadvantages of various reagents to complement as applied to the diagnosis of different types of rejection in transplants. Activation of the complement cascade produces many split products that do not bind to tissues or that are released from tissues. These fluid-phase products can be detected in plasma, serum, urine, and bronchoalveolar lavage samples. Enzyme-linked immunosorbent assay kits are available to quantitate soluble split products in fluids. Hyperacute rejection is the most unambiguous example of complement-mediated injury to transplants. In hyperacute rejection, complement activation is initiated by large amounts of antibody binding to antigens on the endothelial cells of the transplanted organ. The most characteristic features of hyperacute rejection can be predicted from our knowledge of complement. Complement can be a useful adjunct in diagnosing and directing treatment of transplant rejection. Currently, the tissue-associated final split products of C4b and C3b, namely, C4d and C3d, are the most useful markers of antibody-mediated rejection. Both C4d and C3d offer the advantages of being produced in large amounts and binding covalently to tissues. Monoclonal antibodies to neoantigens on C4d and C3d that are not accessible in the unactivated precursors are available. Although these markers have provided significant diagnostic advances for organ transplantation, appropriate interpretation requires additional information, including testing for circulating antibodies to donor antigens and correlation with clinical evidence of graft dysfunction.

Citation: Baldwin III W. 2006. Complement in Transplant Rejection, p 134-140. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch16

Key Concept Ranking

Major Histocompatibility Complex
0.9686489
Immune Response
0.6100182
Innate Immune System
0.6065906
Enzyme-Linked Immunosorbent Assay
0.5625
0.9686489
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Activation of the early complement components by antibodies. (A) A pair of IgG antibodies is bound by C1 through the C1q subcomponent, and the enzymatic C1r and C1s subcomponents are activated to cleave C4 into C4a and C4b. C4b can bind covalently to a membrane protein and provide an anchor for C2, which is then cleaved. (B) The complex of C4bC2a enzymatically cleaves C3 into C3a and C3b. C3b is structurally homologous to C4b and can bind covalently to a membrane protein. (C) The covalently bound split products of C4 and C3 remain attached to the cell membrane after the antibody, C1, and C2a have dissociated from the membrane. (The sizes of the symbols for C4b and C3b are intended to reflect the potential for larger quantities of C3 than C4 activation products.)

Citation: Baldwin III W. 2006. Complement in Transplant Rejection, p 134-140. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Regulation of C4b and C3b by circulating factor I and leukocytes expressing CR1. (A) CR1, which is expressed by leukocytes, associates with C4b or C3b, allowing factor I to cleave C4b and C3b. (B) The first enzymatic cleavage leaves iC4b or iC3b attached to the cell membrane. (C) Factor I then enzymatically cleaves iC4b or iC3b, and C4d and C3d remain covalently bound to the cell membrane. (As in Fig. 1 , the sizes of the symbols for C4b and C3b are intended to reflect the potential for larger quantities of C3 than C4 activation products.)

Citation: Baldwin III W. 2006. Complement in Transplant Rejection, p 134-140. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Examples of C4d and C3d deposition in organ transplants. (a) Immunofluorescent stain for C3d in an endomyocardial biopsy from a human heart transplant (magnification, ×64). The capillaries have diffuse linear staining. (b) Immunoperoxidase stain for C4d in an experimental cardiac allograft in a rat (magnification, ×16). C4d is deposited in an artery (arrowhead) as well as all of the capillaries (small arrows point to examples). (c) Immunoperoxidase stain for C4d in an experimental lung allograft in a rat (magnification, ×16). The alveolar (Alv) capillaries are stained, as are the endothelial cells of arteries (A), capillaries, and veins adjacent to the bronchiole (Br). (Fluorescein isothiocyanate signal appears white and immunoperoxidase signal appears black in these black-and-white photographs.)

Citation: Baldwin III W. 2006. Complement in Transplant Rejection, p 134-140. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555815905.ch16
1. Baldwin, W. M., III,, E. K. Kasper,, A. A. Zachary,, B. A. Wasowska, and , E. R. Rodriguez. 2004. Beyond C4d: other complement related diagnostic approaches to antibody-mediated rejection. Am. J. Transplant. 4:311318.
2. Bechtel, U.,, R. Scheuer,, R. Landgraf,, A. Konig, and , H. E. Feucht. 1994. Assessment of soluble adhesion molecules (sICAM-1, sVCAM-1, sELAM-1) and complement cleavage products (sC4d, sC5b-9) in urine. Transplantation 58:905911.
3. Bohmig, G. A.,, H. Regele,, M. D. Saemann,, M. Exner,, W. Druml,, J. Kovarik,, W. H. Horl,, G. J. Zlabinger, and , B. Watschinger. 2000. Role of humoral immune reactions as target for antirejection therapy in recipients of a spousaldonor kidney graft. Am. J. Kidney Dis. 35:667673.
4. Dargaville, P. A.,, M. South,, P. Vervaart, and , P. N. McDougall. 1999. Validity of markers of dilution in small volume lung lavage. Am. J. Respir. Crit. Care Med. 160:778784.
5. Dodds, A. W., and , S. K. Law. 1998. The phylogeny and evolution of the thioester bond-containing proteins C3, C4 and alpha 2-macroglobulin. Immunol. Rev. 166:1526.
6. Fearon, D. T.,, M. R. Daha,, T. B. Strom,, J. M. Weiler,, C. B. Carpenter, and , K. F. Austen. 1977. Pathways of complement activation in membranoproliferative glomerulonephritis and allograft rejection. Transplant. Proc. 9:729739.
7. Feucht, H. E. 2003. Complement C4d in graft capillaries—the missing link in the recognition of humoral alloreactivity. Am. J. Transplant. 3:646652.
8. Fidler, M. E.,, J. M. Gloor,, D. J. Lager,, T. S. Larson,, M. D. Griffin,, S. C. Textor,, T. R. Schwab,, M. Prieto,, S. L. Nyberg,, M. B. Ishitani,, J. P. Grande,, P. A. Kay, and , M. D. Stegall. 2004. Histologic findings of antibody-mediated rejection in ABO blood-group-incompatible living-donor kidney transplantation. Am. J. Transplant. 4:101107.
9. Jordan, J. E.,, M. C. Montalto, and , G. L. Stahl. 2001. Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury. Circulation 104:14131418.
10. King, K. E.,, D. S. Warren,, M. Samaniego-Picota,, S. Campbell-Lee,, R. A. Montgomery, and , W. M. Baldwin III. 2004. Antibody, complement and accommodation in ABO-incompatible transplants. Curr. Opin. Immunol. 16:545549.
11. Kissmeyer-Nielsen, F.,, S. Olsen,, V. P. Petersen, and , O. Fjeldborg. 1966. Hyperacute rejection of kidney allografts associated with pre-existing humoral antibodies against donor cells. Lancet ii:662665.
12. Kuypers, D. R.,, E. Lerut,, P. Evenepoel,, B. Maes,, Y. Vanrenterghem, and , B. Van Damme. 2003. C3D deposition in peritubular capillaries indicates a variant of acute renal allograft rejection characterized by a worse clinical outcome. Transplantation 76:102108.
13. Mauiyyedi, S., and , R. B. Colvin. 2002. Humoral rejection in kidney transplantation: new concepts in diagnosis and treatment. Curr. Opin. Nephrol. Hypertens. 11:609618.
14. Miller, G. G.,, L. Destarac,, A. Zeevi,, A. Girnita,, K. McCurry,, A. Iacono,, J. J. Murray,, D. Crowe,, J. E. Johnson,, M. Ninan, and , A. P. Milstone. 2004. Acute humoral rejection of human lung allografts and elevation of C4d in bronchoalveolar lavage fluid. Am. J. Transplant. 4:13231330.
15. Nickeleit, V., and , M. J. Mihatsch. 2003. Kidney transplants, antibodies and rejection: is C4d a magic marker? Nephrol. Dial. Transplant. 18:22322239.
16. Ollert, M. W.,, J. V. Kadlec,, K. David,, E. C. Petrella,, R. Bredehorst, and , C. W. Vogel. 1994. Antibody-mediated complement activation on nucleated cells. A quantitative analysis of the individual reaction steps. J. Immunol. 153:22132221.
17. Patel, R., and , P. I. Terasaki. 1969. Significance of the positive crossmatch test in kidney transplantation. N. Engl. J. Med. 280:735739.
18. Platt, J. L. 2002. C4d and the fate of organ allografts. J. Am. Soc. Nephrol. 13:24172419.
19. Racusen, L. C.,, R. B. Colvin,, K. Solez,, M. J. Mihatsch,, P. F. Halloran,, P. M. Campbell,, M. J. Cecka,, J. P. Cosyns,, A. J. Demetris,, M. C. Fishbein,, A. Fogo,, P. Furness,, I. W. Gibson,, D. Glotz,, P. Hayry,, L. Hunsickern,, M. Kashgarian,, R. Kerman,, A. J. Magil,, R. Montgomery,, K. Morozumi,, V. Nickeleit,, P. Randhawa,, H. Regele,, D. Seron,, S. Seshan,, S. Sund, and , K. Trpkov. 2003. Antibody-mediated rejection criteria—an addition to the banff 97 classification of renal allograft rejection. Am. J. Transplant. 3:708714.
20. Regele, H.,, M. Exner,, B. Watschinger,, C. Wenter,, M. Wahrmann,, C. Osterreicher,, M. D. Saemann,, N. Mersich,, W. H. Horl,, G. J. Zlabinger, and , G. A. Bohmig. 2001. Endothelial C4d deposition is associated with inferior kidney allograft outcome independently of cellular rejection. Nephrol. Dial. Transplant. 16:20582066.
21. Sacks, S. H.,, P. Chowdhury, and , W. Zhou. 2003. Role of the complement system in rejection. Curr. Opin. Immunol. 15:487492.
22. van den Elsen, J. M.,, A. Martin,, V. Wong,, L. Clemenza,, D. R. Rose, and , D. E. Isenman. 2002. X-ray crystal structure of the C4d fragment of human complement component C4. J. Mol. Biol. 322:11031115.
23. Warren, D. S.,, A. A. Zachary,, C. J. Sonnenday,, K. E. King,, M. Cooper,, L. E. Ratner,, R. S. Shirey,, M. Haas,, M. S. Leffell, and , R. A. Montgomery. 2004. Successful renal transplantation across simultaneous ABO incompatible and positive crossmatch barriers. Am. J. Transplant. 4:561568.
24. Wiggins, R. C.,, P. C. Giclas, and , P. M. Henson. 1981. Chemotactic activity generated from the fifth component of complement by plasma kallikrein of the rabbit. J. Exp. Med. 153:13911404.
25. Williams, G. M.,, D. M. Hume,, R. P. Hudson, Jr.,, P. Morris,, K. Kano, and , F. Milgrom. 1968. “Hyperacute” renal-homograft rejection in man. N. Engl. J. Med. 279:611618.
26. Wolbink, G. J.,, M. C. Brouwer,, S. Buysmann,, I. J. ten Berge, and , C. E. Hack. 1996. CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes. J. Immunol. 157:473479.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error