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Cited by 29T-cell and Retrovirus StudiesInfectious Diseases and TuberculosisCervical and Thoracic Myelopathy

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Cerebrospinal Fluid CXCL10 as a Candidate Surrogate Marker for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

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Tamaki, Keiko, Sato, Tomoo, Tsugawa, Jun, Fujioka, Shinsuke, Yagishita, Naoko, Araya, Natsumi, Yamauchi, Junji, Coler-Reilly, Ariella L. G., Nagasaka, Misako, Hasegawa, Yasuhiro, Yamano, Yoshihisa, Tsuboi, Yoshio·2019·Frontiers in Microbiology
DOI 10.3389/fmicb.2019.02110PMC PMC6749079
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Abstract

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a debilitating, progressive disease without effective treatment; therefore, development of disease modifying therapy that improves long-term functional outcomes is an unmet need for patients. However, it is virtually impossible to consider this as a primary endpoint in clinical trials owing to the prolonged disease course. Therefore, development of surrogate markers that help predict the effectiveness of new interventions is essential. Currently, several candidate surrogate markers have been identified for HAM/TSP. Cerebrospinal fluid (CSF) C-X-C motif chemokine 10 (CXCL10) is involved in the pathogenesis of HAM/TSP and was shown to correlate with disease progression. However, it remains unclear whether changes in CSF CXCL10 levels are observed in response to treatment and whether these correlate with prognosis. Here we investigated several markers, including CSF CXCL10, in this respect. Data pertaining to patient characteristics and results of motor function evaluation and CSF examination of 13 HAM/TSP patients who received steroid treatment were retrospectively analyzed. Osame motor disability scores (OMDS), 10 m walking time, and CSF levels of CXCL10, neopterin, total protein, cell counts, and anti-HTLV-1 antibody titer were compared before and after steroid therapy. Levels of all CSF markers, with the exception of cell count, were significantly decreased after treatment. Nine of the 13 patients (69.2%) showed improvement in OMDS and were considered responders. Pre-treatment CSF levels of CXCL10 and anti-HTLV-1 antibody titer in responders were higher than those in non-responders (p = 0.020 and p = 0.045, respectively). Patients who continued low-dose oral prednisolone maintenance therapy after methylprednisolone pulse therapy showed sustained improvement in OMDS and CSF CXCL10 and neopterin levels lasting for at least 6 months. In contrast, OMDS and the CSF marker levels in patients who discontinued treatment returned to pre-treatment levels after 2–3 months. Our findings suggest that CSF CXCL10 may serve as a therapy-response and therapy-predictive marker for HAM/TSP. In addition, since decrease in CSF CXCL10 level was associated with good functional prognosis, CSF CXCL10 is a potential surrogate marker for treatment of HAM/TSP.

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  • Patients with a short duration of disease and high inflammatory activity have been reported to benefit the most from corticosteroids.

    “Patients with a short duration of disease and high inflammatory activity have been reported to benefit the most from corticosteroids [239,240,241].”

    From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [241]

    The Results (Predictors of Response to Steroid Therapy; page unavailable) report that responders had significantly higher pretreatment CSF CXCL10 levels, supporting the high-inflammatory-activity part of the claim. The paper records disease duration in Table 1 but does not establish that patients with shorter disease duration benefit most from corticosteroids. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Other potential biomarkers for HAM are CSF inflammatory markers, which examine the levels of CXCL10 and neopterin.

    “Other potential biomarkers for HAM are CSF inflammatory markers, which examine the levels of CXCL10 [241] and neopterin [239].”

    From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [241]

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Research works printed but not linked: 27

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Cited by

Sorted by citations

  • Current State of Therapeutics for HTLV-1

    Wang, T. T., Hirons, A., Doerflinger, M., Morris, K. V., Ledger, S., Purcell, D. F. J., Kelleher, A. D., & Ahlenstiel, C. L. (2024) · Viruses · doi:10.3390/v16101616 · Cited by 22

    “…Topical or systemic corticosteroids and mydriatics [263] HTLV-1-associated Sjögren’s Syndrome Artificial lubricants such as saliva/tears replacement solutions coupled with systemic pharmacotherapy with pilocarpine hydrochloride [264] HTLV-1-associated Hashimoto’s thyroiditis and Graves’ disease”
    Background

Metadata

Authors
Tamaki, K., Sato, T., Tsugawa, J., Fujioka, S., Yagishita, N., Araya, N., Yamauchi, J., Coler-Reilly, A. L. G., Nagasaka, M., Hasegawa, Y., Yamano, Y., & Tsuboi, Y.
Affiliations
  • Fukuoka University (JP)
  • St. Marianna University School of Medicine (JP)
Corresponding author
Yamano, Yoshihisa
ORCID
Venue
Frontiers in Microbiology
Publisher
Frontiers Media SA
Published
2019-09-11
Volume
10
Pages
2110-2110
ISSN
1664-302X (ISSN-L)
DOI
10.3389/fmicb.2019.02110
PMC
PMC6749079
OpenAlex
W2971002404
Cited by
29
References
3
Citations by year
2026: 2 · 2025: 5 · 2024: 9 · 2022: 8 · 2021: 3 · 2020: 2
FWCI
1.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Microbiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Japan Agency for Medical Research and Development (JP19ek0109356, JP19ek0109346, JP19ek0109394)
  • Ministry of Health, Labour and Welfare (19FC1007)
  • Japan Society for the Promotion of Science (19K07983, 19H03575, 19K17049, 19K08004)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
  • Health Sciences › Medicine › Surgery › Cervical and Thoracic Myelopathy
Keywords
HTLV-1-associated myelopathy/tropical spastic paraparesis, surrogate markers, corticosteroid therapy, methylprednisolone pulse therapy, neopterin, treatment response prediction, prognosis, disease progression, chemokines

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