CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV-infected patients with syphilis.
BACKGROUND
Asymptomatic neurosyphilis is more difficult to diagnose in human immunodeficiency virus (HIV)-infected patients because HIV itself can cause cerebrospinal fluid (CSF) pleocytosis. The proportion of CSF lymphocytes that are B cells is elevated in neurosyphilis, suggesting that the CSF concentration of the B cell chemoattractant, chemokine (C-X-C motif) ligand 13 (CXCL13) concentration may also be elevated.


METHODS
CSF and blood were collected from 199 HIV-infected patients with syphilis and neurosyphilis. Serum and CSF CXCL13 concentrations were determined.


RESULTS
Patients with neurosyphilis had higher CSF and serum CXCL13 concentrations compared to patients with syphilis but not neurosyphilis. The odds of having symptomatic neurosyphilis were increased by 2.23-fold for every log increase in CSF CXCL13 concentration and were independent of CSF white blood cell and plasma HIV RNA concentrations, peripheral blood CD4+ T cell count and use of antiretroviral medications. A cut-off of 10 pg/mL CSF CXCL13 had high sensitivity and a cut-off of 250 pg/mL or evidence of intrathecal synthesis of CXCL13 had high specificity for diagnosis of both symptomatic and asymptomatic neurosyphilis. CSF concentrations of CXCL13 declined after treatment for neurosyphilis.


CONCLUSIONS
CSF CXCL13 concentration may be particularly useful for diagnosis of neurosyphilis in HIV-infected patients because it is independent of CSF pleocytosis and markers of HIV disease.
Marra
Christina M
CM
Departments of Neurology, University of Washington School of Medicine, Seattle, 98104, USA. cmarra@u.washington.edu <cmarra@u.washington.edu>
Tantalo
Lauren C
LC
Sahi
Sharon K
SK
Maxwell
Clare L
CL
Lukehart
Sheila A
SA
D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002308:Cardiolipins; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid*; D002784:Cholesterol; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D009494:Neurosyphilis / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D010713:Phosphatidylcholines; D012367:RNA, Viral; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013129:Spinal Puncture; D013587:Syphilis / Q000150:complications* / Q000175:diagnosis; D014210:Treponema pallidum / Q000276:immunology
D015415:Biomarkers; C110663:CXCL13 protein, human; D002308:Cardiolipins; D054382:Chemokine CXCL13; D010713:Phosphatidylcholines; D012367:RNA, Viral; C054448:VDRL antigen; D002784:Cholesterol
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