The Prevalence and Significance of HTLV-I/II Seroindeterminate Western Blot Patterns

Abstract

Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15–20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.

Human T-lymphotropic virus-1 serology in the Northern Territory: 2008–2011

“…These band patterns were reviewed against current positive reporting practices including the current NRL guidelines, the World Health Organization (WHO) criteria, and the HTLV European Research Network criteria. 15,16 According to WHO, either gp46 or gp62/68 plus either p19, p24 or p53 is required for a positive diagnosis; the HTLV European Research Network advocates more stringent criteria requiring presence of both p19 and p24 bands plus rgp21 and rgp46-I. In Australia, the NRL requires antibody response to both recombinant envelope proteins (rgp21 and rgp46-I) and/or envelope gp46 plus reactivity to at least three other viral specific proteins of the gag and pol series.…”

A New and Frequent Human T-Cell Leukemia Virus Indeterminate Western Blot Pattern: Epidemiological Determinants and PCR Results in Central African Inhabitants

“…However, they have also been reported in other areas, such as European countries (68), the United States (11,51,73), the Caribbean area (17,57), Central and South America (Brazil, Argentina) (6,35,44,50,61), and more recently the Middle East (74). Most of the studies concern blood donors (10,11,16,63) or epidemiological work in the general population (43) but also organ donors for transplantation (22,36), lactariums (19,58,70), and neurological patients (1,73). Indeed, the finding of an indeterminate WB HTLV serology raises questions not easy to be resolved by the medical doctors in charge of the persons with such an indeterminate pattern.…”

Leukemia and Retroviral Disease

“…In highly endemic regions such as the Caribbean Basin, Central Africa, and southern Japan, more than 1% of the population is infected with HTLV-1 (reviewed in [51] and [52]). Approximately 95% of the individuals infected with HTLV-1 remain as asymptomatic carriers throughout their lives [9,17]. As previously indicated, HTLV-1 is the etiological agent for causing two distinct disease phenotypes, ATL and HAM/TSP, the first involving a CD4 + T-cell malignancy and the second involving a progressive neurological disease.…”

“…Over the years, HTLV-1 has been shown to be associated with the human population for a much longer period of time than the HIV-1 with HTLV-1 being detected in remains of a 1,500 Chilean mummy [16], while HIV-1 sequences have been detected in humans only as far back as the 1920s, many decades before its discovery in the mid-1980s. Based on extensive studies performed over the past three to four decades concerning clinical parameters, epidemiology, molecular biology and virology, immunology, cancer biology, neurobiology, and immuneand neuropathogenesis of HTLV-1 infection, the virus appears to be much more adapted to the human population with greater than 95% of the infected individuals harboring the virus asymptomatically with only small percentages of individuals presenting with symptomatic disease in the form of leukemia or neurologic disease [9,17]. This epidemiologic pattern is quite different than the widespread highly lethal disease of the immune and nervous systems caused by the HIV-1 in the absence of highly active antiretroviral therapy (HAART) [18] (also reviewed in [19]).…”