Human T-Lymphotropic Virus (HTLV) I/II Immunoblot Confirmation

The MP Diagnostics HTLV Blot 2.4 is a qualitative enzyme immunoassay intended for confirming the presence of and differentiating antibodies to HTLV-I and HTLV-II in human serum and plasma. It is intended for use as a supplemental (additional, more specific) test for human serum and plasma samples with repeatedly reactive results by an FDA licensed HTLV-I/II donor screening test. The MP Diagnostics HTLV Blot 2.4 is intended for use in a manual mode or a semi-automated mode using the MP Diagnostics AutoBlot System 20. This test is not intended for use in medical diagnosis.

About HTLV

Human T-cell Lymphotropic Viruses (HTLVs) are pathogenic retroviruses that may cause severe hematological and neurological diseases in infected individuals. The HTLV family has two well-studied members: HTLV-I and HTLV-II. HTLV-I is known as the etiological agent of adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis. Although less pathogenic than HTLV-I, HTLV-II infection has been associated with leukemia and neurological disease but the causal relationship remains uncertain.

Studies of the geographic distribution of HTLV-I infection reveal that the HTLV-I virus is highly prevalent in Japan, Africa, the Caribbean Islands, and South America. Recent epidemiological studies in the United States and Europe confirm the presence of a mixed prevalence of both HTLV-I and HTLV-II among different high-risk populations, such as intravenous drug users and transfusion recipients. The viruses can be transmitted through sexual contact, through contaminated blood products, and from mother to child via breastfeeding.

Screening tests for HTLV-I/II are available although limited. Repeatedly reactive specimens from screening tests require additional more specific tests to confirm HTLV seropositivity including discrimination of HTLV-I and HTLV-II seropositives. These supplemental assays (i.e. type-specific peptide EIAs, ELISAs, or Western blots) must be capable of identifying antibodies to core (gag) and envelope (env) proteins of HTLV-I and HTLV-II. Western blot strips incorporating HTLV-I native viral antigens are one such commonly used supplemental test.

Screening of whole blood donations for the presence of antibodies to HTLV-I/II has been required in the United States since 1988. Simple yet specific and sensitive supplemental serological tests are therefore needed to enable rapid confirmation and differentiation of HTLV-I and HTLV-II seropositive samples. A supplemental test is essential to provide additional key information necessary for donor counseling, follow-up testing, and/or treatment.

The MP Diagnostics HTLV Blot 2.4 is intended as a supplemental (additional more specific), test to confirm the presence of anti-HTLV-I/II antibodies in blood donor specimens repeatedly reactive on an FDA licensed screening test and to differentiate between HTLV type-I and HTLV type-II infections for donor notification and counseling. The possible serological profiles defined by the HTLV Blot 2.4 include the following: HTLV-I Seropositive, HTLV-II Seropositive, HTLVI/II Seropositive, Seronegative and Indeterminate.

The MP Diagnostics HTLV Blot 2.4 uses a combination of HTLV-I/II genetically engineered proteins (i.e., recombinant antigens) and HTLV-I viral proteins derived from native, inactivated viral particles (i.e., viral lysate). The differentiation between HTLV-I and HTLV-II is accomplished through the use of rgp46-I, a unique HTLV-I envelope recombinant protein, and rgp46-II, a unique HTLV-II envelope recombinant protein. Both proteins are derived from the central region of the external glycoprotein, gp46, of HTLV-I and HTLV-II respectively. GD21, a common yet specific HTLV-I and HTLV-II epitope envelope recombinant protein derived from a truncated region of p21e (rgp21), is also used to enhance the specificity of envelope antibody detection: GD21 has demonstrated better specificity over p21e⁷³, an earlier version of the recombinant antigen. The antigenicity exhibited by these recombinant proteins is either common to HTLV-I and HTLV-II antibodies or type specific to one of the two viral types to allow confirmation and differentiation in a single assay. Additional differentiation between HTLV viral types is effected using gag proteins p19 and p24; if p19 is greater than or equal to p24, HTLV-I infection is suggested, and if p24 is greater than p19, HTLV-II infection is suggested^67-71. Test performed by Viromed/LabCorp 1447 York Ct., Burlington, NC 27215. This test has not been cleared or approved for diagnostic use by the U.S. Food and Drug Administration. See package insert for more information.