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The Bacchanal Buzz of Antibodies in Heart Transplantation

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David P Nelson, MD
ISHLT HFTM Council Communications Liaison
Chief, Heart Transplant Medicine Division
INTEGRIS Nazih Zuhdi Transplant Institute
Oklahoma City, Oklahoma, USA

At the 2013 ISHLT meeting in Montreal, the Heart Failure and Transplant Scientific Council chose to have members submit citations with a brief synopsis of interesting articles published in journals outside ISHLT. Below are my evaluations of three citations which might be of interest to heart failure and transplant medicine specialists. In addition, Howard Eisen contributed a report for this issue entitled, mTOR Inhibition: Where We Have Been, Where We Are, And Where We (Hopefully) Will Be Going, which you don't want to miss.

Role of anti-vimentin antibodies in allograft rejection, Rose ML, Human Immunology (2013), doi. Comments by Dr. David Nelson based on unedited manuscript accepted for publication.

Marlene Rose's excellent review of anti-vimentin antibodies (AVA) in this issue provided the following points:

  1. AVA probably results from tissue damage coupled with inflammation.
  2. Rejection injury is a prerequisite for AVA acceleration of rejection.
  3. The mechanism of AVA acceleration or accentuation of rejection may include the proinflammatory effects of complement fixation and pro-thrombotic effects of platelet activation.
  4. AVA are not inhibited by CyA but are more suppressed by mycophenolate than azathioprine.
  5. AVA may be associated with cardiac graft vasculopathy.
  6. Higher AVA titers occur in recipients of non-heart-beating long-ischemic-time kidneys than heart-beating short-ischemic-time kidneys.
  7. One study showed renal transplants with pre-transplant AVA IgG had higher incidence of chronic graft vasculopathy.
  8. Prolonged dialysis may increase AVA.
  9. Unpublished study by Rose ML and Smith JD found AVA IgM in 10% and 6%, respectively, of 350 heart and 458 lung candidates (pretransplant). AVA IgG was not measured.
  10. Rose cites Nath et al's study in this journal (Journal of Heart and Lung Transplant 77:1604-1609, 2004) as demonstrating an association between AMR and AVA.

Vimentin antibody production in transplant patients and immunomodulatory effects of vimentin in-vitro, Carter V and Howell W. M. Comments by Dr. David Nelson based on unedited manuscript accepted for publication.

Vaughan Carter and W. Martin Howell compared AVA levels in end-stage heart, lung, kidney, and liver patients to 100 blood donors and found that AVA were mostly IgM and mostly found in end-stage liver patients and kidney re-transplant candidates. Primary biliary cirrhosis was the major AVA risk in the liver group, and HLA DQ2 was the AVA predictor in the failing kidney graft group. Primary biliary cirrhosis is an autoimmune disease and DQ2 is associated with autoimmune diseases such as SLE and celiac disease. Some of the renal transplant patients were biopsy C4d positive with negative HLA DSA and responded to plasma exchange.

Banff Initiative for Quality Assurance in Transplantation, (BIFQUIT): Reproducibility of C4d Immunohistochemistry in Kidney Allografts, Mengel, et. al., American Journal of Transplantation 2013; 13:1235-1245, comments by Dr. David Nelson.

In 2009 the Banff initiative for quality assurance in transplantation (BIFQIT) was developed to assess and improve reproducibility of C4d immunohistochemistry (IHC) reported in kidney transplantation. The first BIFQIT trial was published recently by Mengal et al in the American Journal of Transplantation, 2013; 13:1235-1245. Unstained slides were sent to 73 institutions for staining by local protocols and interpretation and then returned to a central panel for re-interpretation. The results showed that:

  1. There was poor inter-institutional reproducibility (Kappa 0.17).
  2. The institutional variability was equally due to inter-observer (Kappa 0.44) and inter-laboratory (Kappa 0.46) limitations.
  3. The central panel read higher scores than local labs, which the authors suspected was the result of local pathologists adjusting their scores to their local clinical experience.
  4. False positives were uncommon.
  5. The study suggested that simplification of histologic grading would improve reproducibility. Reproducibility was best with C4d negative and strongly positive slides. Intermediate grades were where the most variability occurred.
  6. Four specific recommendations for tissue staining and processing were provided (table 4 of the article).
  7. The authors note that alternative criteria for renal AMR is being evaluated in recognition of reported C4d negative AMR.

Disclosure statement: The author has no conflicts of interest to disclose.

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