Maybe I am being paranoid but this post seems a little suspicious to me. Note this is the first post made by this individual
.hhhhmmm
.and its about lung transplants
. hhhhmmmm.
Well, I dont want to be unfriendly so welcome Path2008. The timing of your post is suspicious to me only because recently there has been some critisim of pathology programs without heart and lung transplant on this message board. But, Ill give you the benefit of the doubt and will take what may potentially be bait.
I happened to train at an institution that only did kidney transplantsno heart and lung transplant program. However, interestingly enough one of the more recent additions to my old program (Cornell) has a research interest in lung transplants and interstital lung disease. In fact she is pretty well published in that arena. See for yourself at
www.pubmed.com and type in Magro C [au] + lung into the search box. Now she is more well-known as a dermatopathologisteveidently a very controversial dermatopathologistbut she actually wrote a letter (which addresses what you bring up) in response to this article
(
http://ajrccm.atsjournals.org/cgi/reprint/172/8/944?ijkey=3d21b9a74120267c255cd3e93b6c738413662d9a)
which is in the American Journal of Respiratory and Critical Care Medicine. Here is Dr. Magros take on your questions.
Lung transplantation: opportunities for research and clinical advancement.
Am J Respir Crit Care Med 2006 feb 15; 172(8): 466-7.
We read with great interest the article by Wilkes and colleagues that summarized the scientific and clinical advancements in lung transplantation (1). We would like to expand on the advancements that have been made in the area of humoral rejection. Wilkes and coworkers describe the association of soluble C4d in bronchoalveolar lavage fluid and the presence of anti-HLA antibodies. In their study, a definitive correlation between C4d levels in the bronchoalveolar lavage fluid and clinical status could not be established, resembling the lack of correlation between clinical status and soluble complement levels in other solid organ settings. In contrast, in situ work on C4d expression in lung tissue has shown that higher levels of C4d expression in lung allograft biopsies are a marker of acute and chronic graft dysfunction, analogous to those described in other solid organ transplant settings (2). While anti-HLA antibodies may be a predictor of acute rejection and bronchiolitis obliterans syndrome (BOS), clinical and pathologic findings compatible with humoral rejection and the development of BOS can be seen in the absence of HLA antibodies (3). Such findings suggest that the implicated antigens, namely, those of endothelial- and/or epithelial-based origin, may not be exclusively HLA related.
Wilkes and coworkers indicate that microarrays using rodent models have shown up-regulation of antibody and complement genes in the transplanted lung (1). Morphologic and clinical correlates of this interesting molecular observation have been described in humans. For example, a pauci-inflammatory necrotizing capillary injury phenomenon affecting the septal microvasculature with concomitant immunoreactant microvascular deposition correlates with clinical features of acute rejection (4). In the same vein, additional antigen targets comprising the bronchial epithelium, bronchial wall microvasculature, and chondrocytes by virtue of immunoreactant localization to these aforesaid bronchial wall components have been reported (5). Ultrastructurally, septal microvascular changes virtually identical to those described in the kidney are observed in patients with BOS. Both the kidney and lung changes have fallen under the general rubric of transplant capillaropathy (6). Such vascular changes are attributable to repetitive humorally mediated microvascular injury. High levels of C3d deposition within the septal microvasculature may also be a predictor of chronic graft dysfunction/BOS (7).
In conclusion, humoral immunity in the context of lung transplantation may involve a spectrum of antigenic targets that are not always HLA related. Its occurrence is not a rarity but perhaps even common, and finally, its contribution to chronic graft dysfunction may be significant.
Cynthia M. Magro, Amy L. Pope-Harman, Abbas E. Abbas and Patrick Ross, Jr
So, thats Dr. Magro from an ACADEMIC point of view. She basically agrees with you Path2008, those are interesting questions that need to be addressed. I havent really been interested in transplant pathologyin generalbut Dr. Magro gave a great grand rounds last year about some of her other lung transplant/ immunology research. It was very interesting. I havent kept up with the literature in this area because, 1) its not my area of interest 2) I am really busy with my fellowship which is surgical oncological pathology 3) Even though I may wind up at an instituton at which lung transplants are performed I will likely never sign those cases out as I not going into transplant pathology. I am pretty sure that lung transplants are only done at a handful of institutions in this country and that at those institutions there are generally one or two attendings who sign out all those cases.
Anyway, good luck to you in your studies. Like I said, I have never been a big fan of transplant pathology but I did find Dr. Magros ideas interesting and the papers of hers that I have read are excellent.
