Untitled - Roche Trasplantes

PROTOCOL BIOPSIES AND THE DIAGNOSIS OF HUMORAL REJECTION
ated rejection (Figure 9): according to this model, the first evidence of a humoral response
is the de novo generation of donor-specific antibodies (stage I). However, in many circumstances
and for unknown reasons, donor-reactive antibodies do not elicit acute humoral
rejection. The next stage (stage II) fit the criteria (see below) of accommodation
(=grafts resistance to antibody = C4d detectable in allograft without pathology and dysfunction)
and are therefore not necessarily predestined to lead to allograft injury. In stage
III, in addition to positive staining for C4d, there are identifiable pathological features of
humoral rejection, but allograft function is still normal (i.e., subclinical humoral rejection).
Finally, in stage IV, in addition to positive staining for C4d and morphological signs of humoral
rejection, clinically overt allograft dysfunction occurs. At this point in most cases
already chronic allograft damage with often non specific changes like tubular atrophy or
interstitial fibrosis, or even with for a humoral pathogenesis specific features like glomerulopathy
or capillaropathy can be seen.
Hypothesized stages of humoral rejection
I II III IV
Graft dysfunction
(clinical chronic rejection)
Graft injury (pathology in graft biopsy)
Transplant
C4d detectable in graft microvasculature
De novo antibodies detectable in circulation
Antibodies first
produced
Time (not to scale)
Graft loss
Figure 9. Proposed sequence of stages of antibody-mediated rejection as first suggested
by R. B. Colvin, Department of Pathology, Massachusetts General Hospital, Boston, MA.
However, detecting C4d at a very early time point after transplantation in clinically stable
allografts by protocol biopsies (taken at day seven after transplantation) was of highly predictive
marker for the onset of increasing titers of newly produced donor-specific antibodies.
No C4d deposition was seen in preimplantation biopsies in these patients. Early
detection of C4d and donor-specific antibodies was not associated with an inferior posttransplant
allograft outcome at one-year follow-up, even without specific treatment in this
study. This observation further supports the above mentioned hypothesis that early and
mild humoral responses might be part of an accommodation process.
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