False-positive human T-lymphotropic virus serology after intravenous immunoglobulin transfusion

Abstract

A cute biphenotypic leukemia was diagnosed in a 29-year-old man who had previously been well. The patient immediately started a course of intensive induction chemotherapy; however, the leukemia was refractory. The patient required a total of 3 courses of chemotherapy before achieving complete remission.After his first course of chemotherapy, the patient felt weakness in both of his legs and numbness in his toes, and he was unable to urinate. A clinical examination showed upper motor neuron signs. The weakness improved with physiotherapy, but the numbness rapidly progressed during the second course of chemotherapy and subsequently stabilized with a sensory level at T5. The results of magnetic resonance imaging (MRI) of the patient's spine were normal, and an electroneuromyogram showed mixed polyneuropathy. The results of a lumbar puncture were unremarkable, leading us toward a diagnosis of toxic myelopathy, secondary to chemotherapy. We gave the patient 97.5 g (1g/kg body weight, intravenously) of immunoglobulins (Gamunex Biotherapeutics Inc.) empirically.As part of the neurologic investigation, we performed serologic testing the day after the patient received the immunoglobulins; the results showed reactivity on an enzyme immunoassay for human T -lymphotropic virus (HTLV). Tests to confirm infection were done at the National Laboratory for HIV Reference Services: an INNO-LIA HTLV I/II Score assay (Innogenetics, Belgium) returned a positive result, and the results of an in-house radioimmunoprecipitation assay were indeterminate. The final interpretation of these tests was indeterminate (Table 1). A polymerase chain reaction (PCR) test for HTLV could not be done.The patient and his parents were born in Canada. He was in a monogamous relationship, did not engage in high-risk behaviours and had never travelled to HTLV-endemic regions such as Asia. The result of repeat MRI of the patient's spine was normal. Baseline serologic testing for HTLV, done when the patient's leukemia was diagnosed, was negative (Table 1). A serum sample taken 2 weeks before the positive screening test was retrospectively analyzed and was found to be negative for HTLV. Follow-up serologic testing on a whole blood sample collected 2 months later returned negative results, including PCR testing for the HTLV-I and HTLV-II tax gene sequences. Finally, a sample of cerebrospinal fluid collected at the 2-month follow-up was tested; the results of all investigations were negative.Of note, the serum collected on the day after the patient received the immunoglobulin transfusion showed positive treponemal serology (Captia TA, Trinity Biotech), with negative non treponemal serology (Rapid Plasma Reagin; Pulse Scientific Inc.) and negative confirmatory tests for treponemal organisms (Treponema pallidum particle agglutination assay [Fujirebio] and syphilis INNO-LIA Score [Innogenetics]). Serologic testing for syphilis could not be done on the serum that had been collected before the immunoglobulin transfusion was given. However, 8 weeks after the transfus...

Misleading hepatitis B testing in the setting of intravenous immunoglobulin

“…A false positive enzyme immunoassay and a Treponema pallidum haemagglutinin assay have also been reported following IVIG infusion 4 , 5 . Positive human T-lymphotropic virus (HTLV) testing following IVIG infusion for chemotherapy-induced polyneuropathy has also been reported in a leukemic patient resulting in a delay in his cord blood transplantation 6 . In all the above cases, repeated testing 4–8 weeks post IVIG revealed lower or negative antibody titers.…”

Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin

“…IVIG administration is known to confound serologic diagnosis of infections with pathogens such as human T-lymphotropic virus and Toxoplasma ( 5 , 6 ). This report describes 10 patients in which administration of IVIG confounded the diagnosis of human rabies.…”

Search for serological markers of infection in transfused patients: are the limitations of these assays always clear?

“…In this case it is difficult to understand if the presence of IgG is actually generated by a post infection seroconversion or by passive transfer following transfusion. No doubt that in these cases other microbiological investigations must be carried out: in addition to search for the presence of IgG in the donor (which may not be diriment or easy to be performed), the detection of pathogen nucleic acids by molecular biology techniques in transfused patient can help solving the problem (1). Being the issue clear and in case of strong clinical suspicion, clinicians should not only rely their diagnosis on serology testing but should prescribe, when available, pathogen specific molecular biology tests.…”

“…For other markers of infection not routinely screened on blood donations, the situation is even more problematic because it is difficult to determine the presence of specific antibody in the blood product (1). For the diagnosis of many different infections antigen specific IgG and IgM are normally sought.…”