Human T-Lymphotropic Virus Types I, II - HTLV I, II

Diagnosis

Indications for Testing

  • Clinical presentation of adult T-cell leukemia/lymphoma (ATLL) or HTLV-I associated myelopathy (HAM) in patient with risk factors (eg, IV drug use, multiple sex partners, residence in endemic area)
  • Undiagnosed myopathy or myelopathy

Criteria for Diagnosis

Laboratory Testing

  • Required evaluation for ATLL (according to Shimoyama criteria, 1991)
    • Peripheral blood smear – ATLL cells present
    • HTLV-I antibody testing
      • Initial test – HTLV-I and -II antibodies by EIA/Western blot
        • HTLV-II antibodies significantly cross-react to HTLV-I antigens
        • Populations such as parenteral drug abusers infected with HTLV-II may test positive for HTLV-I antibodies due to antibody cross-reactivity
      • Asymptomatic patients with HTLV-I antibodies
        • May be infected and should not donate blood
        • May not have ATLL or tropical spastic paraparesis (TSP) and may not develop ATLL, HAM, or TSP
      • Proviral loads correlate with infectivity
    • HTLV-I, II PCR – use to resolve untypable or indeterminate HTLV Western blot results when there is a strong suspicion of HTLV infection
  • CSF studies
    • Protein – increased
    • Cell differential – lymphocytic pleocytosis
    • HTLV antibodies – positive
    • Oligoclonal bands – positive
    • IgG index – high
  • Bone marrow exam – generally not required

Histology

  • If diagnosis not obtained by above, perform lesion biopsy (if present)
  • Immunophenotyping
    • Minimum testing should include CD3, CD4, CD7, CD8, and CD25
    • Most ATLL cells lack CD7, CD52 with diminished CD3
    • CD4+ T-cells express CD2, CD5, CD25, CD45RO, CD29
    • CD7 and CD26 negative and CD3 expression diminished

Imaging Studies

  • CT – recommend neck, thorax, abdomen, and pelvis to exclude extranodal disease
  • Upper gastrointestinal endoscopy
  • Central nervous system evaluation by CT/MRI if neurologic signs evident

Prognosis

  • Poor prognosis risk factors
    • Serum LD elevated
    • Serum calcium elevated
    • Age ≥40
    • Three or more lesions
    • Additional – thrombocytopenia, eosinophilia, high IL5, p53 or p16 deletion

Differential Diagnosis

Clinical Background

Human T-cell lymphotropic virus type I (HTLV-I) is etiologically associated with adult T-cell leukemia/lymphoma (ATLL); tropical spastic paraparesis (TSP), a demyelinating neurological disorder; and with HTLV-I-associated myelopathy (HAM).

Epidemiology

  • Prevalence – 15-20 million infected with HTLV-I worldwide
    • Endemic in Japan, Caribbean countries, and sub-Saharan Africa
  • Age
    • T-cell leukemia /lymphoma – 60 years mean
    • HAM/TSP – 40s-50s
  • Sex
    • ATLL – M>F
    • HAM/TSP – M<F
  • Transmission
    • Parenteral
    • Sexual
    • Breast-feeding
  • Lifetime risk of disease in the presence of HTLV-I antibodies is low
    • ATLL – men have increased risk for progression compared to women
    • HAM/TSP – 0.5-4%

Organism

  • HTLV-I and HTLV-II are human type C retroviruses
    • Several subtypes exist that are geographically specific
      • HTLV-I – six subtypes (A-F)
    • Single-stranded RNA virus
  • Majority of human infections caused by subtype I
  • HTLV and AIDS
    • HTLV-I does not cause AIDS
    • Antibodies of HTLV-I have no relationship to antibodies of human immunodeficiency virus type I (HIV-I)
      • Antibodies to HTLV-I do not imply excess risk for AIDS
    • HTLV-I virus is only remotely related to HIV-I, the AIDS virus
    • HTLV-I and HTLV-II are transmitted similarly to HIV-I and HIV-II
    • Individuals with HTLV-I or HTLV-II may be coinfected with HIV due to common risk factors (eg, sexual contact, IV drug use)

Risk Factors

  • Cellular blood products – most efficient mode of transmission
  • Breast milk – 20% of children of infected mothers will also become infected
  • Sexual contact – associated with unprotected sex, multiple partners, presence of genital sores, sex exchanged for drugs or money
  • Sharing of contaminated needles and syringes (eg, IV drug use)
  • HTLV-I positive mother – perinatal transmission may occur
  • Poverty

Clinical Presentation

  • ATLL
    • 4 types – acute, chronic, smoldering, lymphoma
    • Acute ATLL most common
      • Rapidly fatal without treatment
      • Pulmonary complications, opportunistic infections, sepsis
      • Uncontrolled hypercalcemia may occur
  • TSP and HAM
    • Slowly progressive spastic paraparesis – disease usually present 8-10 years before diagnosis
    • Prominent weakness of lower extremities with severe spasticity
      • Upper extremity weakness rare
      • Mild sensory impairment
      • Hyperreflex is often present
      • Neuropathic pain is common in advanced stage
    • Bladder/bowel/sexual dysfunction later in disease
      • Urinary tract infections, lithiasis, chronic pyelonephritis, chronic renal failure
    • Other associated diseases

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Human T-Lymphotropic Virus (HTLV) Types I/II Antibodies by ELISA with Reflex to HTLV-I/II Confirmation by Western Blot 0051164
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Screen for antibodies to HTLV-I and II

Assay should not be used for blood donor screening, associated re-entry protocols, or for screening human cell, tissues, and cellular and tissue-based products

 
Human T-Lymphotropic Virus Types I/II DNA, Qualitative Real-Time PCR 2003075
Method: Real-Time Polymerase Chain Reaction

Resolve untypable or indeterminate HTLV Western blot results when there is a strong suspicion of HTLV infection

   
Human T-Lymphotropic Virus Types I/II Antibodies, Western Blot 0020642
Method: Qualitative Western Blot

Confirm antibody test results for a positive screening test (HTLV types I and II) performed in another lab

 

If results are untypable or indeterminate, repeat test in 3 months

Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003
Method: Flow Cytometry

Aid in evaluation of hematopoietic neoplasms (ie, leukemia, lymphoma)

Monitor therapy in patients with established diagnosis of hematopoietic neoplasms

Specimens include peripheral blood, bone marrow, and tissue

Markers selected based on clinical history, previous flow studies, and pathologist interpretation

Available markers:

T cell: CD1, CD2, CD3, CD4, CD5, CD7, CD8, TCR alpha-beta, TCR gamma-delta, cytoplasmic CD3

B cell: CD10, CD19, CD20, CD22, CD23, CD103, kappa, lambda, FMC7, cytoplasmic kappa, cytoplasmic lambda

Myelo/Mono: CD11b, CD13, CD14 (Mo2), CD14 (MY4), CD15, CD33, CD64, CD117, myeloperoxidase

Misc: CD11c, CD16, CD25, CD30, CD34, CD38, CD41, CD42b, CD45, CD56, CD57, CD61, HLA-DR, glycophorin, TdT, bcl-2, ALK-1, CD123, CD138, CD200, CD26, CD45

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic
Calcium, Serum or Plasma 0020027
Method: Quantitative Spectrophotometry
Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry
Cell Count, CSF 0095018
Method: Cell Count/Differential
Oligoclonal Bands in CSF and Serum 0081135
Method: Qualitative Isoelectric Focusing/Electrophoresis