Basic Immunobiology of TransplantationIPNA

Gamal Saadi MDEm Prof of Int Med & Nephrology

Cairo University

Longer-term outcomes remain a challenge in kidney transplantation

ANZDATA 31st annual report 2008 (http://www.anzdata.org.au/anzdata/AnzdataReport/31stReport/Ch08Txpart2.pdf)

Primary graft survival of deceased donors by year of transplant to 31/12/07: Australia and NZ

Genetic barriers to transplantation

Antibodies in transplantation

• Hemaglutinins (ABO): natural

• HLA

• MIC-A, MIC-B, KIR.

• ANTIENDOTHELIUM: XM-ONE

• Abs against ATII receptor: malignant HTN

• ANTIVIMENTINE & other antibodies

Immunobiology of Tx

ØThe blood group antigens are represented on the vascular endothelium and represent an important barrier for transplantation

ØThe Rhesus factor is not relevant to the process of graft rejection

ØYet Rh identity was significantly related to better graft outcome of 5% after 5 years

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Short limb of

Chromosome 6

Short limb of

Chromosome 6

Polymorphic HLA specificities and their inheritance

HLA matching

• Initial CTS analysis and Eurotransplant data showed that the major impact comes from the DR and B antigens, with little additional effect from the A antigens

Opelz G, Transplantation 1985 Sep;40(3):240-3Opelz, G. Collaborative Transplant Study Newsletter 1988; (3)

Coupel S; et al, Kidney Int 2003 Aug;64(2):674-80 Doxiadis II;et al, Transplantation. 2007 May 15;83(9):1207-13www.ustransplant.org/annual-reports, accessed August 2007

S. Takemoto et al. Human Immunology 65, 1489–1505 (2004)© American Society for Histocompatibility and Immunogenetics, 2004

HLA matching

• "taboo" mismatches were specific HLA mismatch combinations are associated with decreased renal allograft survival

• avoidance of mismatches is used in preference to matching of HLA

Doxiadis II;et al, Lancet 1996 Sep 28;348(9031):850-3

Transplant outcome

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• TerEp #17 is equivalent to the 62GE epletrepresented on A2, B57 and B58similar molecular configuration on A*0201 (Figure 1A) and B*5701 (Figure 1E)

R. J. Duquesnoy & M. Marrari, Tissue Antigens ISSN 0001-2815

S. Takemoto et al. Human Immunology 65, 1489–1505 (2004)© American Society for Histocompatibility and Immunogenetics, 2004

Tissue-typing methods to screen kidney transplant candidates for anti-HLA antibodies.

Marfo K et al. CJASN 2011;6:922-936

©2011 by American Society of Nephrology

Detection of HLA antibodies

• Class-I HLA antigens are present on T cells (+) & B cells (++)

• Class-II HLA antigens are present on B cells only

• T cell –ve / B cell +ve cross match represents class-II Abs (of less significance) as well as low titres of class-I Abs

• T cell +ve / B cell –ve cross match is indicative of non HLA Abs

Sellares J et al. AJT 2011

Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence

The a-Gal problem

Cooper DKC, Proc (Bayl Univ Med Cent) 2012 Jan; 25(1): 49–57

inactivation of one particular porcine gene

addition of human genes

Cooper DKC, Proc (Bayl Univ Med Cent) 2012 Jan; 25(1): 49–57

Allospecific matching is the Key stone of ensuring graft survival

Immunosuppression and Adherence is the corner stone of maintaining graft survival

Thank you