Published ahead of print on April 12, 2006
Clin J Am Soc Nephrol 1: 399-, 2006
© 2006 American Society of Nephrology
doi: 10.2215/CJN.00720206
Moving Points in Nephrology |
Antibodies Come Back to the Forefront in Transplantation
Flavio Vincenti
Kidney Transplant Service, University of California San Francisco, San Francisco, California
Address correspondence to: Dr. Flavio Vincenti, University of California San Francisco, Kidney Transplant Service, 505 Parnassus Avenue, Room 884M, San Francisco, California 94143-0780. Phone: 415-476-4496; Fax: 415-353-8974; E-mail: vincentif{at}surgery.ucsf.edu
In 1969, Terasaki introduced the cross-match, a simple and elegant test to uncover patients who are presensitized to donor alloantigens. Over time, this test was modified to increase its sensitivity, especially by the incorporation of flow cytometry to further improve the detection of donor-specific antibodies (DSA). With the threat of hyperacute rejection almost eliminated, the focus of diagnosis and treatment shifted to the T cell. Despite the effectiveness of anti-T cell therapies introduced in the 1980s and 1990s and the associated reduction in acute rejection rates, long-term survival has not increased appreciably. In fact, acute rejection has become less likely to be reversed fully, and many patients develop irreversible damage after an episode of rejection. Two important observations have catapulted humoral immunity back to a prominent role in the fate of the graft. Visualization of C4d by immunohistochemistry in renal allografts provided the basis for linking humoral rejections with a wider spectrum of histologic manifestations of DSA-mediated rejection, both in the acute setting and in patients with chronic renal dysfunction. The second development was the realization that patients who develop de novo anti-HLA antibodies had a significantly higher risk for subsequent graft loss. The clinicohistologic manifestations of humoral immunity in renal transplantation, the mechanism of injury by antibodies, and the challenge of managing and treating highly sensitized patients are updated in these Moving Points: Paul Terasaki and Kazuo Mizutani discuss the magnitude of the problem and impact on renal allograft of antibody-mediated rejection in kidney transplantation, Stanley Jordan and Mark Pescovitz review the management of presensitization, Lorraine C. Racusen and Mark Haas describe the histology of antibody-mediated rejection in renal allografts, Enver Akalin and Manuel Pascual expound on the various methods of antibody detection, and Kathryn J. Tinckan and Anil Chandraker elucidate the mechanism of injury of both HLA and non-HLA alloantibodies. T cells are still important in alloresponses, but B cells and their antibodies now can reclaim their rightful place in the pathogenesis of renal allograft dysfunction.
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Published online ahead of print. Publication date available at www.cjasn.org.
