CSF CXCL10, CXCL9, and neopterin as candidate prognostic biomarkers for HTLV-1-associated myelopathy/tropical spastic paraparesis.

Abstract

BACKGROUND:

Human T-lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic neuroinflammatory disease. Since the disease course of HAM/TSP varies among patients, there is a dire need for biomarkers capable of predicting the rate of disease progression. However, there have been no studies to date that have compared the prognostic values of multiple potential biomarkers for HAM/TSP.

METHODOLOGY/PRINCIPAL FINDINGS:

Peripheral blood and cerebrospinal fluid (CSF) samples from HAM/TSP patients and HTLV-1-infected control subjects were obtained and tested retrospectively for several potential biomarkers, including chemokines and other cytokines, and nine optimal candidates were selected based on receiver operating characteristic (ROC) analysis. Next, we evaluated the relationship between these candidates and the rate of disease progression in HAM/TSP patients, beginning with a first cohort of 30 patients (Training Set) and proceeding to a second cohort of 23 patients (Test Set). We defined "deteriorating HAM/TSP" as distinctly worsening function (≥3 grades on Osame's Motor Disability Score (OMDS)) over four years and "stable HAM/TSP" as unchanged or only slightly worsened function (1 grade on OMDS) over four years, and we compared the levels of the candidate biomarkers in patients divided into these two groups. The CSF levels of chemokine (C-X-C motif) ligand 10 (CXCL10), CXCL9, and neopterin were well-correlated with disease progression, better even than HTLV-1 proviral load in PBMCs. Importantly, these results were validated using the Test Set.

CONCLUSIONS/SIGNIFICANCE:

As the CSF levels of CXCL10, CXCL9, and neopterin were the most strongly correlated with rate of disease progression, they represent the most viable candidates for HAM/TSP prognostic biomarkers. The identification of effective prognostic biomarkers could lead to earlier detection of high-risk patients, more patient-specific treatment options, and more productive clinical trials.

• Authors: Tomoo Sato, Ariella Coler-Reilly, Atae Utsunomiya, Natsumi Araya, Naoko Yagishita, Hitoshi Ando, Junji Yamauchi, Eisuke Inoue, Takahiko Ueno, Yasuhiro Hasegawa, Kusuki Nishioka, Toshihiro Nakajima, Steven Jacobson, Shuji Izumo, Yoshihisa Yamano
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 7 Issue 10 Pg. e2479 ( 2013) ISSN: 1935-2735 [Electronic] United States
• PMID: 24130912 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• CXCL10 protein, human
• CXCL9 protein, human
• Chemokine CXCL10
• Chemokine CXCL9
• Neopterin

Topics

• Adult
• Aged
• Biomarkers (cerebrospinal fluid)
• Chemokine CXCL10 (cerebrospinal fluid)
• Chemokine CXCL9 (cerebrospinal fluid)
• Disease Progression
• Female
• HTLV-I Infections (diagnosis)
• Humans
• Male
• Middle Aged
• Neopterin (cerebrospinal fluid)
• Prognosis
• ROC Curve
• Retrospective Studies
• Young Adult