1. Effects of Humoral Antibodies in Organ Transplantation: Boon or Bane? Reference: Ponticelli C. Humoral antibodies in organ transplantation: Angels or demons? Am J Transplant. 2010;10:1332.

2. Kidney transplant biopsies, which were done late in the posttransplant course found out the development of de novo donor-specifi c antibodies and these were seen linked with specifi c histological lesions in the transplant kidney. The underlying reason is poor diagnosis. In late kidney transplant biopsies, assessment of de novo donor- specifi c antibodies should be performed cautiously. There were many studies which tried to investigate the role of these donor-specifi c antibodies in organ transplantation as they would help in recognizing the pathogenesis of chronic humoral rejection. Although such monitoring is costly, it should be benefi cial and caution is needed to understand the role of humoral antibodies in such situation.

3. There are minor doubts as to whether the circulating antibody caused chronic allograft rejection, but it is not clear if the antidonor antibodies, detected in the circulation are the same as those causing graft injuries. It is accepted that the antibodies are aimed at inducing ‘accommodation’. Evidences from experimental studies indicate that anti- HLA antibodies take part in allograft ‘accommodation’. Allograft accommodation can also be induced through the expression of antiapoptotic genes. The resistance of graft to immune injury favored by antibodies cannot be absorbed by an allograft injured by a previous immunological attack. This results in an increase in the level of antibodies in circulation. The harmfulness or protectiveness of the circulation antidonor antibodies cannot be detected and hence, therapeutic decisions should be made carefully based on their measurement. Removal therapies are started, if the antidonor antibodies have a detrimental effect on graft outcome.

4. Preventing the chronic rejection and prolonging renal allograft survival depends on the initial detection of alloantibody. As of now, there are no convincing facts showing that therapies are based on apheresis, B-cell removal or proteasome inhibition which are of any signifi cant benefi t in the treatment or prevention of chronic rejection. Apart from this, these therapies can be harmful if the potentially protective alloantibodies are removed, as the circulation also involves these alloantibodies operating in human allografts. It is therefore suggested to be safe to not alter the intensity of immunosuppression until further studies come up with a detailed true nature and the heterogeneity of circulation antibodies, because reinforcement of immunosuppression may lead to serious or even life-threatening side-effects.