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

Anna Abrams,Yoshimi Akahata,Steven Jacobson

doi:10.3390/v3081320

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.

Highlights

The first detection of the Human T-lymphotropic virus type I (HTLV-I) in 1980 marked the identification of the first human retrovirus [1]
Numerous 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
The Western blot (WB) used to confirm seropositivity in an enzyme immunoassay (EIA) positive patient sample utilizes recombinant proteins specific for HTLV-I/II Env glycoproteins incorporated into the WB strips

Summary

Background

The first detection of the Human T-lymphotropic virus type I (HTLV-I) in 1980 marked the identification of the first human retrovirus [1]. We have developed a luciferase immunoprecipitation systems (LIPS) assay that has increased specificity and sensitivity in anti-HTLV-I antibody detection [9] These new methodologies have helped to shed light on the prevalence of the virus, indicating that approximately 15–20 million individuals worldwide are infected with HTLV-I. In Japan, 20% of HAM/TSP patients reported a history of blood transfusion as opposed to 3% of normal donors (p < 0.001) [11] Due to this increased risk of disease with blood transfusion, many screening methods have been employed to detect HTLV-I infected donors. Japan in 1986, the United States in 1988, France in 1991, and the Netherlands in 1993 [10,11] These screenings were initiated once proof of increased risk for developing HAM/TSP was definitively associated with transfusion. States include initial testing by an enzyme immunoassay (EIA), followed by confirmation of seropositivity by WB [12]

Defining and Identifying Seroindeterminates

Cross-Reactivities to Other Retrovirus

Low Copy Number of Prototype HTLV-I

Findings

Current Research and Future Directions