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. 2025 Oct 3;74(1):137.
doi: 10.1007/s00011-025-02102-8.

Peripheral inflammation in spinocerebellar ataxia type 3: associations with genetic and clinical manifestations

Jia-Yi Zhang #  1   2 , Qiu-Ni Su #  3 , Han Lin #  1   2 , Wei Lin  1 , Mao-Lin Cui  1   4 , Zhuo-Ying Huang  1 , Bei-Ning Ye  1 , Ying-Xin Ye  1 , Yi-Lin Jia  1   2 , Qing-Ying Zhu  1   2 , Zhi-Han Li  1   2 , Min-Ting Lin  1   5   6 , Ning Wang  7   8   9 , Bing-Long Wang  10 , Shi-Rui Gan  11   12   13 ; OSCCAR Investigators
Affiliations

Peripheral inflammation in spinocerebellar ataxia type 3: associations with genetic and clinical manifestations

Jia-Yi Zhang et al. Inflamm Res. .

Abstract

Background: Neuroinflammation plays a recognized role in the pathogenesis of Spinocerebellar Ataxia Type 3 (SCA3). However, the involvement of systemic inflammatory responses in SCA3 remains poorly defined.

Objectives: Our study aimed to characterize peripheral inflammation in patients with SCA3, examine the relationship between peripheral inflammatory biomarkers and clinical/genetic features, and evaluate the diagnostic utility of these markers.

Methods: The cross-sectional study enrolled 101 patients with SCA3 and 101 healthy controls (HCs). The differences in peripheral inflammatory markers between patients with SCA3 and HCs were assessed. Multivariate linear regressions were used to analyze the associations between blood cell count-derived indices, C-reactive protein (CRP), and clinical/genetic features of SCA3. ROC curves were conducted to assess the potential of these markers to distinguish patients with SCA3 from HCs.

Results: Compared to HCs, patients with SCA3 exhibited significantly higher levels of leukocytes, neutrophils, monocytes, platelets, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory index (SII), systemic inflammatory composite index (AISI), and CRP (adj. p < 0.05). Age influenced lgCRP, NLR, MLR, and lg(neutrophil-to-platelet ratio) (p < 0.05). CAG affected MLR and AISI (p < 0.05). The combination of BMI, monocytes, NLR, and SII differentiated patients with SCA3 from HCs (AUC = 0.779).

Conclusion: Patients with SCA3 display distinct peripheral inflammatory profiles, which correlate with clinical/genetic factors. These peripheral inflammatory markers hold promise as potential tools for diagnosing and monitoring SCA3.

Keywords: Biomarker; Blood cell count-derived inflammatory indices; Neuroinflammation; Peripheral Inflammation; Spinocerebellar ataxia type 3.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Consent to participate: Informed consent was obtained from all participants or their legal representatives. Ethics approval: Approval was obtained from the Ethics Committee of the First Affiliated Hospital of Fujian Medical University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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