2013 - IXA 2013 Congress


Early Morning Educational Lecture 1: Differences between anti-HLA Abs and anti-carbohydrate Abs (Main Room)

13.4 - Accommodation: Lessen from clinical cases

Presenter: Kazuhide, Saito, Heidelberg, Japan
Authors:


ABO-incompatible kidney transplantation (ABOI-KTx) has been considered to be immunologically high risk since preformed natural anti-donor A/B carbohydrate antibody would frequently cause “hyperacute” or “delayed hyperacute” severe antibody mediated rejection(AMR) resulted in graft thrombosis and loss for a long time. However, from our precise and careful clinical and pathological observation, except for iatrogenic few cases, hyperacute rejection within 48 hours hardly occurred (silent period). After that, acute AMR likely to occurred during the critical period for 1 to 2 weeks, then, we found that immunological accommodation would be induced in majority of the cases.  

 In 2004, we have defined that “accommodation refers to the lack of reaction between

ABO blood group antigens on the surfaces of endothelial cells within the graft and these antibodies in the blood of the recipient, i.e. graft survival without antibody-mediated

rejection.” In the recent decade, we have learned much from a lot of clinical cases and have revealed the mechanism of the development of AMR and induction of accommodation, and established the theoretical basis of the desensitization therapy.

 We have also revealed that AMR in ABOI-KTx can be broadly classified into two categories based on antigen stimulation and immunological response to the stimulation. This classification applies not only to kidney transplants but also to other ABOI-organ transplants.

 Type I AMR occurs in highly sensitized recipients when the transplant kidney themselves become stimulating antigens provoking an immunological second-set response that results in explosive antibody production. It occurs early in the critical period and is primarily characterized by the massive elevation of anti-A/B IgG antibody titer with parallel elevation of anti-IgM titer. If this reaction once occurs, AMR is sometimes difficult to be controlled. Usually these patients show high anti-A/B IgG titer before treatment and antibody rebound is frequently seen after pretransplant antibody removal. In these cases, it is essential to perform pretransplant desensitization procedures.

 Type II AMR sometimes occurs after bacterial infection such as sepsis, blood group carbohydrate antigen analogues on the bacterial cell surface act as cross reactive antigen stimulation to the host and elicit the sensitization. The host will be sensitized and produce variety of polyclonal anti-carbohydrate antibodies in which some portion would react with A/B antigens on the endothelial surface and damage the kidney graft. Since this is a primary response to initial sensitization, it takes some time before antibody production. So the type II AMR occurs in the late phase of the critical period. The pathology progresses more slowly and is less severe than type I. Anti-A/B IgM antibody titer is typically elevated, in some cases, IgG elevation does not occur. Type II AMR could be predicted, in some instance, preventable, and possibly controlled and treatable by anti-rejection therapy with antibiotics against bacterial infection.

 This phenomenon could occur because of the biomimetic sensitization.

 In this lecture, we would like to introduce typical cases and talk about effective prevention, desensitization and treatment against AMR in ABOI-KTx.


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