Intrathecal Synthesis Index of Specific Anti-
            <i>Treponema</i>
            IgG: a New Tool for the Diagnosis of Neurosyphilis

Alberto, Chloé; Deffert, Christine; Lambeng, Nathalie; Bréville, Gautier; Gayet-Ageron, A; Lalive, Patrice H.; Trellu, Laurence Toutous; Fontao, Lionel

doi:10.1128/spectrum.01477-21

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…The newly reported CSF biomarkers CXCL13, 21 neurogranin, 22 and the intrathecal synthesis index of specific anti-Treponema IgG 23 have been shown to be valuable for the diagnosis of neurosyphilis. However, etiological and serological detection of syphilis in CSF is not commonly performed before the patient shows obvious symptoms of neurosyphilis due to the disadvantages and patient nonacceptance of lumbar puncture, which results in patients missing the opportunity for early antipsychotic treatment.…”

Section: Discussionmentioning

confidence: 99%

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

Shen¹,

Dong²,

Liu³

et al. 2022

IDR

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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.

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Section: Discussionmentioning

confidence: 99%

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

Shen¹,

Dong²,

Liu³

et al. 2022

IDR

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“…Intrathecal anti-treponemal antibody production supports the diagnosis of active neurosyphilis, and with the use of the TPHA index, patients with abnormal CSF can be better classified in regard to their need for neurosyphilis therapy ( 35 ). However, careful interpretation of the AI result is still crucial due to the lack of a “gold standard” ideal cutoff, although measuring an AI for specific T. pallidum antibodies is a new potential tool for NS diagnosis ( 36 ). The high CSF treponemal-specific antibody response is a consequence of inflammatory pathology of the central nervous system ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Intrathecal immunoglobin synthesis and its role in patients with neurosyphilis

Huang

Ying

Luo

et al. 2022

Front. Public Health

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BackgroundIntrathecal protein synthesis (ITS) occurs in various central nervous system disorders, but few quantitative studies have focused on ITS for neurosyphilis (NS) in southwestern China. We made a study to quantitatively assess the ITS in patients with NS and to investigate the association between ITS and the stages of NS.MethodsCSF–serum specimen pairs from 142 patients (66 NS and 76 non-NS/syphilis) were collected for routine CSF and serum tests. The NS group was divided into slight and severe subgroups according to the NS stages. Three formulas for the quantitative determination of the intrathecal synthesis were calculated to characterize the specimens, including the Ig index (QIg/Qalb), Ig extended index (Ig_EI), and intrathecally synthesized fraction (IgIF) using the hyperbolic function. The role of QTPPA/QIgG as an antibody index (AI = Q specific Ig/QIgG) was also explored.ResultsSero_TRUST titres (1:16, 1:1-1:256), sero_TPPA titres (1:163840, 1:1280-1:1310720), total protein (MTP), and CSF_Igs (p < 0.05) were found to be significantly elevated in the NS group. Intrathecal Ig synthesis can be identified using all three formulas in the NS group. The pattern of Ig intrathecal synthesis was IgIF-G (48.62%) > IgIF-A = IgIF-M (p < 0.05), with the dominant intrathecal fraction being IgG (median, 48.62%), which was also verified by QIgG> Qalb> QIgM = QIgA. In the slight NS group, the intrathecal fractions of IgM (>0 in 4 out of 20 cases) and IgG (>0 in 16 out of 20) were lower than the intrathecal fractions of IgM (>0 in 19 out of 35 cases) and IgG (>0 in 33 out of 38) in the severe group (p < 0.05). The area under the curve (AUC) of the CSF_TPPA antibody index was 0.867 (0.792, 0.922), with an optimal cutoff point of 0.81, providing a sensitivity of 88.91% and specificity of 84.62%.ConclusionAlthough the intrathecal synthesis pattern is IgG dominant in patients with NS, brain-derived IgM and IgA can also be found. Moreover, intrathecal IgM and IgG were associated with a parenchymatous type of neurosyphilis. Syphilis-specific antibodies are a new potential tool for NS diagnosis.

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“…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).…”

Section: New Diagnostic Indicators and Strategies (N)mentioning

confidence: 99%

CARE-NS, a research strategy for neurosyphilis

Zhang²,

Zhang³

et al. 2023

Front. Med.

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Neurosyphilis is a major clinical manifestation of syphilis. In recent years, an increase in neurosyphilis cases has been reported in many countries. The overall incidence of neurosyphilis remains unknown, and there is a lack of understanding of the disease pathogenesis, which hampers clinical management, development of prevention strategies, and control. This article proposes the CARE-NS research strategy to enhance the clinical management of neurosyphilis, which consists of six key features: comprehensive management including multidisciplinary treatment (C), alleviating neurological impairment and sequelae (A), risk factors and clinical epidemiology (R), etiology and pathogenesis (E), new diagnostic indicators and strategies (N), and social impact and cost-effectiveness analysis (S).

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Intrathecal Synthesis Index of Specific Anti- Treponema IgG: a New Tool for the Diagnosis of Neurosyphilis

Cited by 7 publications

References 30 publications

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

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

Intrathecal immunoglobin synthesis and its role in patients with neurosyphilis

CARE-NS, a research strategy for neurosyphilis

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