Anti-HLA Antibodies Detected by CDC Associated With Lower Survival After Lung Transpl

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Anti-HLA Antibodies Detected by CDC Associated With Lower Survival After Lung Transplant


Katherine Kahn, DVM

July 28, 2006 (Boston) — The presence of anti-HLA antibodies in patients before lung transplantation detected by complement dependent cytotoxicity (CDC) is associated with worse survival than in nonsensitized patients, a new study confirms. However, there was no difference in survival between sensitized and nonsensitized patients using flow cytometry testing. Sandeep Gupta, MD, a fellow in heart and lung transplantation at the Cleveland Clinic in Ohio, presented the findings here at the World Transplant Congress.

"Anti-HLA antibodies in other solid organs such as heart and kidneys are well established in terms of their negative effect on survival," Dr. Gupta told Medscape, "but the role of anti-HLA antibodies in lung transplants is less well understood."

To examine this relationship, Dr. Gupta and colleagues retrospectively looked at data from 448 adult first-time lung transplantations performed at the Cleveland Clinic from 1990 to 2005.

Of these, 438 had been tested using CDC. A total of 296 patients had undergone flow cytometry, which was introduced in 1993.

Of the patients tested using CDC technology, 17 (3.8%) had a panel reactive antibody (PRA) higher than 10% and 8 patients (1.83%) had a PRA higher than 25% for class I antibodies. Class I sensitized patients, defined as patients with a PRA higher than 10%, had significantly lower survival rates than class I nonsensitized patients (P = .0035). Class I nonsensitized patients had survival rates of 79.4% at 1 year posttransplant, 63.2% at 3 years, and 45.4% at 5 years. Sensitized patients had 1, 3, and 5 year survival rates of 64.7%, 28.8%, and 9.6%, respectively.

Of the patients tested using CDC technology, cytotoxic class I and II PRAs accurately predicted cross-matching.

"We wanted to see if these results [using CDC testing] were corroborated using flow cytometry," Dr. Gupta told meeting attendees. "It's well-established in heart and kidney transplantation that flow cytometry is very sensitive in picking up anti-HLA antibodies; however, in lung transplantation we do not know if there is a correlation with survival."

Flow cytometry detected class I antibodies in a higher percentage of patients than CDC, with 38 (12.8%) of 296 patients having a PRA higher than 10% and 17 patients (5.74%) having a PRA higher than 25%. Nonsensitized patients had 1, 3, and 5 year survival rates of 83.1%, 66%, and 48%, respectively. Sensitized patients had 1, 3, and 5 year survival rates of 78.1%, 66.4%, and 33.2%, respectively. The difference was not statistically significant (P = .23).

In addition, researchers compared survival rates of patients with a positive class I and class II cross-matches detected by flow cytometry, and those with negative cross-matches. There was no statistical difference.

"Seventy-seven percent of patients who had class I positive cross-match by flow cytometry had no history of HLA sensitization," Dr. Gupta said during his presentation. "So something else was causing them to have a positive cross-match." Researchers ruled out auto-antibody cross-matches and the possibility that they were using too low of a cut-off point for the cross-match, Dr. Gupta said.

Other possible explanations for why flow cytometry results did not correlate with survival include careful selection of compatible donors using virtual cross-matching technology, and aggressive immunosuppression of sensitized patients.

James Allan, MD, a thoracic surgeon at Massachusetts General Hospital in Boston, and the moderator of the session, commented to Medscape on the study's findings. "Some of the techniques we are currently using to detect anti-HLA antibodies have gotten so sensitive and so good, that they are actually detecting antibodies that may not have clinical relevance.

He continued, "Flow cytometry PRA is very sensitive in detecting anti-HLA antibodies, but then once we detect them, we have to figure out what to do with that information. That information could have absolutely no clinical implication — or it could be very significant, so what the results mean have to be considered on a patient-to-patient basis." He added that studying this in lung transplantation is difficult because the subset of sensitized patients is relatively small.

The study was independently funded. The authors report no relevant financial relationships.

World Transplant Congress 2006: Abstract 620. Presented July 25, 2006.