Untitled - Roche Trasplantes
Untitled - Roche Trasplantes
Untitled - Roche Trasplantes
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BIOPSIA DE PROTOCOLO EN EL TRASPLANTE RENAL<br />
However, as shown from animal models or in sequential allograft indication biopsies C4d<br />
often can precede the onset of chronic humoral rejection, but the interval between the<br />
stages can be very variable and quite long, and it is not known whether progression is<br />
inexorable. Therefore, prospective long term follow-up is needed for cases of subclinical,<br />
C4d positive humoral rejection to clarify whether this is an unavoidable precursor of<br />
chronic humoral rejection or a sign of accommodation. Since current therapy for cases<br />
of acute humoral rejection can be related to various sever side effects more data are<br />
needed to further support already at an early time point (subclinical C4d detection without<br />
pathology = stage II) a specific therapeutic intervention for the prevention of chronic<br />
humoral rejection.<br />
ACCOMMODATION AND HUMORAL REJECTION<br />
Accommodation is defined as the resistance of an allograft to the acute pathological effects<br />
of allograft-specific antibodies and complement activation. This phenomenon was<br />
already observed in the late eighties in recipients of an ABO-incompatible renal allograft.<br />
Transient depletion of the circulating antibodies that are specific for the blood group antigens<br />
at the time of transplantation allows immediate allograft survival without hyperacute<br />
rejection. However, in 90% of the cases a rebound of the antibodies with high titers in<br />
patient’s serum leads to humoral rejection within the first 10 days. But the remaining<br />
showed no correlation between the occurrence of humoral rejection and antibody titers<br />
within the next 21 days. Even if the antibody titers return to pre-transplant levels or higher,<br />
the allografts continue to function. Findings from mice models showed that, in the absence<br />
of T-cell help (e.g., due to an initial conditioning regime), B-cells that are exposed<br />
to incompatible antigens on allografts differentiate into cells that can produce non-complement-fixing<br />
antibodies, and these B cells gradually become tolerant after a prolonged<br />
exposure.<br />
In HLA-mismatched allografts, alloantibodies can be found in the absence of clinical graft<br />
dysfunction, herewith fulfilling the criteria of accommodation. However, patients with circulating<br />
HLA-specific anti-donor antibodies have a greater likelihood of later allograft loss,<br />
indicating that, if accommodation occurs under transplant conditions, then it is either transient<br />
or insufficient to prevent chronic humoral rejection. Long term, complete accommodation<br />
has not been documented for MHC molecules in humans so far, and the phenomenon<br />
might therefore be partly determined by the nature of antigen.<br />
Several molecular pathways should be involved in accommodation. A central role is most<br />
probably located within the allografts’ endothelium which is thought to express cytoprotective<br />
proteins like anti-apoptotic BCL-2, BCL-X, and haem oxygenase 1 (HO-1).<br />
Increased expression of BCL-X was found in the endothelium of renal allografts from patients<br />
with circulating donor-specific antibodies. Furthermore, HLA-class-I-specific antibodies<br />
increase endothelial-cell expression of BCL-2, BCL-X, and HO-1, and increase the<br />
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