1,721,064 research outputs found
Immunological issues in clinical composite tissue allotransplantation: where do we stand today?
No full textComposite tissue allografts are made of histogenetically different tissues and although skin seems to be the most antigenic of them, it is unknown whether the dominant immune response is really directed against the skin or we have insufficient information on the involvement of the other components of these allografts. The first clinical signs of acute rejection manifest on the skin and microscopically the earliest lesions consist in a dermal perivascular lymphocytic infiltrate, predominantly made of CD3+/CD4+ T cells. On the basis of the histological changes, a specific score (Banff score 2007) has been established to assess the severity of rejection. Despite the high incidence of acute rejection episodes, they can be completely reversed when promptly diagnosed and treated. C4d deposits in the skin and circulating donor-specific antibodies are rarely detected, suggesting that humoral rejection does not play a significant role in composite tissue allotransplantation. Chronic rejection features are still unknown. The majority of recipients have been maintained on an immunosuppressive regimen consisting of tacrolimus, steroids, and mycophenolate mofetil. The complications in composite tissue allotransplantation are similar to those usually reported after solid organ transplantation and have prompted different strategies to minimize the maintenance immunosuppression or to induce donor-specific tolerance. Furthermore, to what extent the immunosuppression can be tapered is unknown, as well as the influence of donor bone-marrow infusion in tolerance and chronic rejection. The increasing number of patients and the longer follow-up hopefully will allow answering these questions
Chronic rejection in vascularized composite allotransplantation
No full textPURPOSE OF REVIEW:
Vascularized composite allografts (VCA), which restore severely damaged body parts that cannot be repaired with conventional surgical techniques, often undergo acute skin rejection episodes in the early postgraft period. Although the risk of human VCA to be affected by chronic rejection was initially unknown, such cases were recently observed.
RECENT FINDINGS:
Chronic rejection targets preferentially the skin (dermal sclerosis, adnexal atrophy, necrosis) and vessels (graft vasculopathy) and may cause graft dysfunction, often resulting in ischemic graft loss. Both immune (cell-mediated and antibody-mediated) and nonimmune mechanisms seem to be involved. The early diagnosis and management of chronic rejection are challenging. Changes of chronic rejection may be seen macroscopically on the skin and can be confirmed with skin and deep tissue biopsies. New noninvasive imaging techniques, which allow visualization of the allograft vasculature, seem promising for the noninvasive detection of graft vasculopathy.
SUMMARY:
Although some features of chronic rejection of VCA start to be known, several important questions remain to be answered, concerning namely the proper definition of chronic rejection, precise diagnostic criteria, better understanding of triggering factors and pathogenetic mechanisms involved and, most importantly, adequate treatment. Ideally, chronic rejection should be prevented in the future by efficient tolerance-inducing protocols
Self-renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft
No full textEpidermal Langerhans cells (LC) are dendritic, antigen-presenting cells residing within mammalian epidermis and mucosal epithelia. When massively depleted, they are replaced by cells of bone-marrow origin. However, their renewal within normal skin under steady-state conditions is not precisely known. We observed that epidermal LC within a human hand allograft remain stable in the long term (10 years) and are not replaced by cells of recipient's origin; furthermore, we observed a Langerhans cell in mitosis within the epidermis 8 years postgraft. These results show that under almost physiological conditions, human LC renew in the epidermis by local mitoses of preexisting cells
Ultrastructural study of chronic lesions of erythema elevatum diutinum: "extracellular cholesterosis" is a misnomer.
No full textGraft vasculopathy in the skin of a human hand allograft: implications for diagnosis of rejection of vascularized composite allografts
No full textWhereas vascularized composite allografts often undergo acute rejections early in the postgraft period, rejection manifesting with severe vascular changes (graft vasculopathy) has only been observed on three occasions in humans. We report a hand-allografted patient who developed severe rejection following discontinuation of the immunosuppressive treatment. It manifested clinically with erythematous maculopapules on the skin and pathologically with graft vasculopathy that affected both large vessels and smaller cutaneous ones. The observation that graft vasculopathy can affect skin vessels shows that it is amenable to diagnosis with usual skin biopsy as recommended for the follow-up of these allografts. Graft vasculopathy developing in the setting of vascularized composite allografts likely represents chronic rejection due to under-immunosuppression and, if confirmed, should be included in a future update of the Banff classification of vascularized composite allograft rejection
Alopecia areata in a composite tissue (hand) allograft recipient following graft rejection.
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