PROPOSED CLASSIFICATION OF HUMAN COMPOSITE TISSUE ALLOGRAFT ACUTE REJECTION

 

LC Cendales, MD1 and DE Kleiner, MD, PhD2.

lTransplant and Autoimmunity Branch, NIDDK, National Institudes of Health, Bethesda, MD, 20892 and 2National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 United States of America

 

Composite Tissue Limb Allotransplantation (CTA) has recently been introduced clinically as a treatment for limb loss. In the past 4 years 20 limbs have been transplanted in 16 patients. Most have experienced reversible episodes of acute rejection. Though rejection has been presumed to be mediated by mechanisms similar to solid organ transplantation, a systematic examination of the inflammatory infiltrate has not been performed. Furthermore, since CTA is a new discipline, no formal scheme for grading rejection has been established. We therefore collected 11 specimens from transplanted human limbs in various stages of clinical rejection (mild to terminal at amputation). Specimens have been stained for routine histology as well as immunohistochemical classification of the infiltrate, and ranked according to severity from 1-10 for overall infiltration, destruction of adnexa and epidermis, and involvement of the various CT A elements. In general, CTA rejection was seen initially as a perivascular infiltrate that then involved the dermis with progression to arteritis as the process advanced. Myositis was also seen in some of the biopsies but it is not clear how the severity fits with the dermal changes. Although perineural involvement was seen, frank neuritis was not seen even in advanced rejection. Thus, elements of the graft appear capable of eliciting an immune response. Immunohistochemical studies showed that the infiltrate in the milder cases was composed predominantly of CD4+ T -cells versus more severe cases that were predominantly composed of CD8+ T-cells.  lnterestingly, HLA-DR was only minimally expressed in keratinocytes even in severe rejection, unlike the T-cell mediated cases of graft versus host disease. Based on this initial survey we propose the following preliminary classification system to initiate a standardization process for CT A reporting. Grade 0: No pathologic changes. Non-specific changes, no or only mild lymphocytic infiltration with no involvement of the superficial dermal vessels. Grade I-Mild: perivascular inflammation in the superficial dermis without involvement of the overlying epidennis or adnexa. Grade II-Moderate: features of Grade I with focal involvement of the epidermal layer of adnexal structures or overlying epidermis. Grade III-Severe: Bandlike superficial dermal infiltrate with more continuous involvement of the epidermis and middle and deep perivascular infiltration. Studies in a CT A non-human primate model are ongoing and comparative routine histology and immunohistochemistry will be shown.

 

 

 

 

 

 

 

PROPOSED CLASSIFICATION OF HUMAN COMPOSITE TISSUE ALLOGRAFT ACUTE REJECTION

 

LC Cendales, MD1 and DE Kleiner, MD, PhD2.

lTransplant and Autoimmunity Branch, NIDDK, National Institudes of Health, Bethesda, MD, 20892 and 2National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 United States of America

 

Linda Cendales MD

NIDDK, NIH

Center Drive 10, 11S 219

Bethesda, MD  20892

USA

 

Tel:  (301) 496-3037

Fax:  (301) 480-0488