Serum Interleukin-26 is a Potential Biomarker for the Differential Diagnosis of Neurosyphilis and Syphilis at Other Stages

Abstract

Background Interleukin-26 (IL-26) is an atypical proinflammatory cytokine due to its binding to circulating double-stranded DNA and direct antibacterial activity. Although IL-26 has been confirmed to be involved in the pathophysiology of cancer, chronic inflammatory diseases and infections, the diagnostic and prognostic values of IL-26 levels in syphilis patients are not clear. This study aimed to investigate IL-26 levels in different stages of syphilis progression. Methods A total of 30 healthy controls and 166 patients with syphilis at different stages of disease progression were enrolled. Serum IL-26 levels were quantified in accordance with the protocols of RayBio ® Human Interleukin-26 Enzyme Linked Immunosorbent Assay (ELISA) kits. Clinical laboratory diagnostic parameters and blood analysis data were detected and collected according to clinical medical laboratory standards. Results The levels of serum IL-26 were significantly higher in neurosyphilis patients than in healthy subjects (6.87 (4.36, 12.14) and 1.67 (0.09, 4.89) pg/μL, respectively; ****p < 0.0001), latent syphilis (1.48 (0.40, 2.05) pg/μL, ****p < 0.0001), seroresistant syphilis (0.81 (0.20, 2.91) pg/μL, ****p < 0.0001) and secondary syphilis (1.66 (0.41, 4.25) pg/μL, ****p < 0.0001) with data presented as the median with interquartile range. The concentration of serum IL-26 was most sensitive to serum low-density lipoprotein concentration (r = −0.438, **p = 0.004) in latent syphilis, urine epithelial cells (r = 0.459, **p = 0.003) in seroresistant syphilis, and serum creatinine levels (r = 0.463, **p = 0.004) and urea creatinine ratio levels (r = 0.500, **p = 0.008) in secondary syphilis patients. There was no significant correlation with the concentration of IL-26 and toluidine red unheated serum test (TRUST) titers in each type of syphilis patient. Conclusion Circulating IL-26 in serum displays diagnostic potential in the progression of neurosyphilis and warrants further evaluation in clinical trials.

Neutrophil CD64 index as a potential blood biomarker for the diagnosis of neurosyphilis in secondary and tertiary syphilis: A retrospective study

“…Xie et al reported that serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP) and neurofilament light protein (NF-L) had pleasant performances in the diagnosis of NS [ 26 , 27 ]. Shen et al found that circulating IL-26 in serum displayed diagnostic potential in the progression of NS [ 28 ]. Chen et al analyzed the exosomal miRNA profiles in the serum of syphilis patients, and found NS patients showed a significant upregulation in miR-590-5p, miR-570-3p and miR-570-5p [ 29 ].…”

CARE-NS, a research strategy for neurosyphilis

“…Increased concentrations of the chemokines CXCL13, CXCL8, and CXCL10 in the CSF or their CSF/serum ratio, particularly in the case of CXCL13, can predict the occurrence of neurosyphilis (45). In addition, levels of macrophage migration inhibition factor in the CSF, peripheral blood CD8+IFN-γ+ cells, levels of serum IL-26, and antibody index (AI) for intrathecal synthesis of specific anti-treponemal IgG were predictive of neurosyphilis (46)(47)(48)(49). Furthermore, abnormal expression of mir-590-5p, mir-570-3p, mir-570-5p, and mir-21-5p in serum and CSF is another potential biomarker of neurosyphilis (50).…”

Resurgence of syphilis: focusing on emerging clinical strategies and preclinical models

“…Elevated concentrations of CXCL8, CXCL10, and IL-10 may also be potential biological markers of neurosyphilis, especially asymptomatic neurosyphilis [ 37 – 39 ]. Meanwhile, the increased levels of CXCL9, CXCL7, CCL24, IL-17, IL-26, and migration inhibitory factor (MIF) of macrophages in the CSF of neurosyphilis patients suggested their role as promising differential diagnostic tools for neurosyphilis [ 37 , 40 – 42 ]. Although these cytokine changes are still in their infancy for the diagnosis of neurosyphilis, their importance cannot be ignored due to the lack of ideal neurosyphilis biomarkers.…”