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What is the likely impact of graft function in a kidney transplant recipient with positive serology for HTLV-1 and/or HTLV-2?
Jean-Marie Faivre, MD
Human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) are human retroviruses that are distantly related to the more widely recognized retrovirus human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome, or AIDS. Like HIV-1 and other retroviruses, HTLV-1 and HTLV-2 have an RNA genome and possess the enzyme reverse transcriptase. Inside a host cell, these viruses can use this enzyme to transcribe a DNA copy of their genome, which can then be inserted into the host cell genome, leading to latent infection with the virus.
As in the case of HIV-1, infection with HTLV-1 and HTLV-2 is recognized by the presence of antibody to the virus, which is equivalent to infection. The assays most commonly used to detect these viruses do not discriminate between HTLV-1 and HTLV-2, although newer assays that detect each virus separately are available, and some research studies have used direct detection of viral RNA or DNA sequences. Seroprevalence studies have shown that HTLV-1 and HTLV-2 are endemic in southwestern Japan, the Caribbean basin (including Mexico and Central America), Melanesia, and parts of Africa. In the endemic populations, seroprevalence increases with age and can reach 30% to 50% in some parts of Japan. The prevalence in US blood donors is very low, approximately 0.025%. The predominant known modes of transmission are blood transfusion, sexual contact, and mother-to-child transmission. Blood transfusion is the most efficient mode of transmission, with a seroconversion rate of 30% to 50% in individuals receiving a unit of blood from an infected donor.
HTLV-1 is associated with 2 human diseases. The first is an aggressive T-cell lymphoma (adult T-cell lymphoma) with unique clinical features, a poor response to chemotherapy, and a bad prognosis. The second is a progressive demyelinating disorder involving the spinal cord that leads to a spastic paraparesis; this disorder is termed either tropical spastic paraparesis (TSP) or HTLV-1-associated myelopathy (HAM). Curiously, the attack rate of these diseases in the endemic populations is quite low - - the lifetime risk of the lymphoma in infected Japanese has been estimated at 2% to 4% percent; the risk of TSP/HAM is even lower. Little is understood about why 2 such seemingly unrelated diseases are caused by the same virus, how the viruses cause the pathology, or what factors lead to the development of disease in the small fraction of individuals who become affected.
In contrast to HLTV-1, there is no clear association of HTLV-2 with any human disease. In the United States, blood donors have been screened for HTLV-1/2 since 1988. Organ donors are also screened. The current Centers for Disease Control/United States Public Health Service recommendations are that HTLV-1/2-infected individuals should not be used as blood or organ donors, for obvious reasons. There are no official recommendations about transplantation and immunosuppression in infected individuals, although there are some case reports that raise serious concern. The first is a description of a heart transplant patient who became infected with HTLV-1 at the time of cardiac transplantation. Detailed serologic and nucleic acid testing confirmed that the infection was not acquired from the heart donor, but rather from the donor of 1 of several units of blood given during surgery. This patient went on to develop TSP/HAM beginning about 18 weeks after surgery and infection, an unusually rapid course of this disease. The authors believe that the accelerated course may well have been due to the acquisition of the infection in the setting of immune suppression. There is also a case report of a T-cell lymphoma developing in an HTLV-1 infected renal transplant recipient. Although it is difficult to base a recommendation on such a small number of cases, it would seem prudent to avoid transplantation in HTLV-1- and HTLV-2-infected subjects, or only to proceed after a discussion of the risks. The low seroprevalence in US blood donors may argue against routine prelisting screening of all patients in this country, but screening of those from endemic areas is probably justified. Considering the large numbers of subjects from endemic areas in Mexico and Central America living in some parts of the United States, it is conceivable that some US centers may find it advisable to screen everyone.
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