Reuters Health Information (2005-06-01): Immune reconstitution syndrome may occur in organ transplant recipients
Immune reconstitution syndrome may occur in organ transplant recipients
Last Updated: 2005-06-01 15:39:14 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Apparently successful
treatment of Cryptococcus neoformans infection in organ transplant
recipients may be followed by an immune reconstitution syndrome
(IRS)-like illness that is potentially fatal, investigators report in
the June 15th issue of Clinical infectious Diseases.
IRS "is believed to result from enhanced -- but partially
reconstituted -- pathogen-specific, cell-mediated immunity and
induction of proinflammatory cytokines, leading to an exaggerated
inflammatory reaction," explain Dr. Nina Singh, at the University of
Pittsburgh Medical Center, and other members of the Cryptococcal
Collaborative Transplant Study Group. IRS has been particularly
associated with immune restoration in HIV infection.
Dr. Singh's group reports on a series of 83 organ transplant
recipients with cryptococcosis, four of whom developed an IRS-like
entity. The patients ranged in age from 34 to 65 years when they
underwent transplantation (liver, kidney, or kidney and pancreas) with
the initial diagnosis of C. neoformans occurring 3 to 29 months later.
All four were being treated with tacrolimus, mycophenolate mofetil
(MMF) and prednisone as the immunosuppressive regimen when the IRS-like
entity was detected, compared with 21 of the remaining 79 patients
(26.6%, p = 0.007), the authors note, but this was the only significant
difference that they identified.
In all four cases, MMF was discontinued and tacrolimus and
prednisone decreased or discontinued. Two days to 3 months after
instituting antifungal therapy, symptoms of the infection reappeared,
C. neoformans titers increased, but the organism could not be grown in
The IRS-syndrome led to forearm amputation in one patient, while one
patient died 5 months after his initial infection. One patient died of
MI 2 years after the initial infection. The other two patients remain
alive 2 to 3 years later.
"The proposed basis of this phenomenon is reversal of a
predominantly Th2 response at the onset of infection to a Th1
proinflammatory response as a result of receipt of effective antifungal
therapy and a reduction in or cessation of immunosuppressive therapy,"
the study group indicates.
They also speculate that careful use of immunomodulatory agents such
as interferon-gamma may be of use in such cases, with monitoring of
serum levels to avoid a heightened inflammatory response or allograft
J Infect Dis 2005;40:1756-1761.