Immune-inflammatory-nutritional dysfunction in HIV-negative patients with asymptomatic neurosyphilis: a retrospective...

The host's immune function, inflammatory response, and nutritional status are closely related to the occurrence and development of neurosyphilis (NS). Asymptomatic neurosyphilis (ANS), as a completely curable type of NS, has received limited study on these fields. This study explores the immune function, inflammatory response, and nutritional status levels in patients with ANS, as well as their changes after treatment, aiming to provide reference for the early diagnosis and treatment of ANS.

This study retrospectively included 32 healthy controls (HCs), 27 cases of ANS, and 29 cases of syphilis who were treated in our hospital from March 2020 to September 2025. We collected peripheral blood cell/humoral immunity, inflammatory response, and nutritional status indicators from the three groups, compared the differences between them, and analyzed the changes in various indicators of patients with ANS after 6 months of treatment. We used logistic regression analysis to identify independently associated factors for ANS, and constructed receiver operating characteristic (ROC) curves to evaluate the predictive value of influencing factors for its diagnosis.

Compared with the syphilis and HC group, the percentages of natural killer (NK) cells, IgA levels, lymphocyte counts, content of albumin and total protein, and the C-reactive protein-albumin-lymphocyte (CALLY) index in the ANS group were significantly reduced (all p < 0.05), However, the neutrophil counts, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune inflammatory index (SII), and the proportion of blood toluidine red unheated serum test (TRUST) titers ≥1:16 were significantly increased (all p < 0.05). Multivariate logistic regression analysis showed that the low levels of the CALLY index are an independently associated factor for patients with syphilis with concurrent ANS. Its area under the curve (AUC) for predicting ANS is 0.766, with a sensitivity and specificity of 65.5% and 88.9%, respectively. Further analysis showed that the CALLY index in patients with ANS was negatively correlated with white blood cell counts and protein contents of cerebrospinal fluid (CSF) (r = -0.6227, p = 0.0005; r = -0.5690, p = 0.0020). After 6 months of treatment, the neutrophil counts, NLR, PLR, SII, CSF, white blood cell counts, and protein contents in patients with ANS were significantly decreased (all p < 0.01), while the percentage of NK cells and the CALLY index significantly increased (p < 0.05, p < 0.01).

Although patients with ANS are asymptomatic in clinic, there are disturbances in immune function, inflammatory response, and nutritional status. Early standardized treatment may reverse this imbalance. The CALLY index showed preliminary discriminatory ability for the early diagnosis of ANS while it requires validation in large-sample, multicenter cohort studies.