Relevance of Non-HLA Antibodies in Transplantation

Antibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA auto antibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, auto antigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular injury and/or rejection creates permissive conditions for the expression of cryptic auto antigens, allowing these auto antibodies to bind antigenic targets and further enhance vascular inflammation and renal dysfunction. Antiperlecan/LG3 antibodies and angiotensin II type 1 receptor antibodies have been found before transplant in patients with de novo transplants and portend negative long-term outcome in patients with renal transplants. Other auto antibodies documented to have negative effect over the outcome of heart transplant. In addition to the already cited antibodies anti angiotensin II type 1 receptor, these include antibodies against endothelin type A receptor, antibodies anti vimentin and anti myosin. Antibodies against collagen V and Ka1tubulin are associated with the development of bronchiolitis obliterans syndrome. Recently, thanks to new techniques, new non-HLA antibodies have been found whose relevance in transplantation still need to be clarified. Finally, natural antibodies, previously thought to be protective, if present before transplantation in the IgG form have been documented to have a negative effect over the long-term survival of the transplanted organs.