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Peer-reviewedCC BY-NC-ND 4.0Translational Psychiatry

Dual immune dysregulation in adolescent-onset schizophrenia: attenuated B cell trophic support and elevated IL-23/Th17 inflammation are diagnostic and clinical biomarkers

  • Haidong Yang1
  • Lingshu Luan1,2
  • Yubing Han3
  • Sijin Li1,2
  • Man Yang1
  • Xiaobin Zhang4
4 affiliations
  1. 1Department of Psychiatry, Lianyungang Psychiatric Hospital, The Fourth People’s Hospital of Lianyungang, The Affiliated Hospital of KangDa College of Nanjing Medical University, Lianyungang, 222003 China
  2. 2Xuzhou Medical University, Xuzhou, 221004 China
  3. 3The First Clinical Medical College of Xuzhou Medical University, Xuzhou, 221004 China
  4. 4Department of Psychiatry, The Affiliated Guangji Hospital of Soochow University, Suzhou, 215137 China
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Abstract

Adolescent-onset schizophrenia (AOS) is marked by severe symptoms and cognitive impairments, yet its peripheral immune profile remains insufficiently characterized. This cross-sectional study aimed to develop composite immune pathway indices integrating serum B cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), interleukin (IL)-23, and IL-17 levels to reflect immune dysfunction. We examined 93 patients with first-episode, antipsychotic-naive AOS and 40 healthy controls. Five indices were constructed: immune homeostasis protection index (IHPI), BAFF-APRIL immune ratio (BAIR), immune drive-attenuation ratio (IDA), Th17 decoupling index (TDI), and full immune imbalance index (FIII). Serum BAFF (t = −3.324, P = 0.001) and APRIL (t = −3.687, P < 0.001) were significantly reduced and IL-23 was increased (Z = −2.777, P = 0.005), whereas IL-17 remained unchanged (P = 0.292) in patients with AOS. BAIR did not differ between groups (P = 0.741). IHPI was significantly reduced in patients with AOS (t = −5.203, P < 0.001), whereas IDA, TDI, and FIII were elevated (all P < 0.001). Serum IL-23 was independently associated with Positive and Negative Syndrome Scale total score (β = 0.321, P = 0.002) and general psychopathology subscale score (β = 0.320, P = 0.001). In healthy controls, serum BAFF predicted immediate memory (β = 0.408, P = 0.009) and Repeatable Battery for the Assessment of Neuropsychological Status total score (β = 0.444, P = 0.005), an association not observed in patients with AOS. Among composite indices, IHPI achieved the best discriminative performance (AUC = 0.751, sensitivity: 69.9%, and specificity: 72.5%), outperforming individual biomarkers. These findings indicated that dual peripheral immune dysregulation in AOS was characterized by attenuated B cell trophic support and upstream IL-23/Th17 activation, and suggested that composite immune indices may provide incremental diagnostic value over single cytokines.

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Cite

BibTeXRIS
BibTeX
@article{yang2026dual,
  title = {{Dual immune dysregulation in adolescent-onset schizophrenia: attenuated B cell trophic support and elevated IL-23/Th17 inflammation are diagnostic and clinical biomarkers}},
  author = {Haidong Yang and Lingshu Luan and Yubing Han and Sijin Li and Man Yang and Xiaobin Zhang},
  journal = {Translational Psychiatry},
  year = {2026},
  month = jul,
  doi = {10.1038/s41398-026-04343-5},
  url = {https://doi.org/10.1038/s41398-026-04343-5},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Dual immune dysregulation in adolescent-onset schizophrenia: attenuated B cell trophic support and elevated IL-23/Th17 inflammation are diagnostic and clinical biomarkers
AU  - Haidong Yang
AU  - Lingshu Luan
AU  - Yubing Han
AU  - Sijin Li
AU  - Man Yang
AU  - Xiaobin Zhang
PY  - 2026
DA  - 2026/07/30
JO  - Translational Psychiatry
DO  - 10.1038/s41398-026-04343-5
UR  - https://doi.org/10.1038/s41398-026-04343-5
AB  - Adolescent-onset schizophrenia (AOS) is marked by severe symptoms and cognitive impairments, yet its peripheral immune profile remains insufficiently characterized. This cross-sectional study aimed to develop composite immune pathway indices integrating serum B cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), interleukin (IL)-23, and IL-17 levels to reflect immune dysfunction. We examined 93 patients with first-episode, antipsychotic-naive AOS and 40 healthy controls. Five indices were constructed: immune homeostasis protection index (IHPI), BAFF-APRIL immune ratio (BAIR), immune drive-attenuation ratio (IDA), Th17 decoupling index (TDI), and full immune imbalance index (FIII). Serum BAFF (t = −3.324, P = 0.001) and APRIL (t = −3.687, P < 0.001) were significantly reduced and IL-23 was increased (Z = −2.777, P = 0.005), whereas IL-17 remained unchanged (P = 0.292) in patients with AOS. BAIR did not differ between groups (P = 0.741). IHPI was significantly reduced in patients with AOS (t = −5.203, P < 0.001), whereas IDA, TDI, and FIII were elevated (all P < 0.001). Serum IL-23 was independently associated with Positive and Negative Syndrome Scale total score (β = 0.321, P = 0.002) and general psychopathology subscale score (β = 0.320, P = 0.001). In healthy controls, serum BAFF predicted immediate memory (β = 0.408, P = 0.009) and Repeatable Battery for the Assessment of Neuropsychological Status total score (β = 0.444, P = 0.005), an association not observed in patients with AOS. Among composite indices, IHPI achieved the best discriminative performance (AUC = 0.751, sensitivity: 69.9%, and specificity: 72.5%), outperforming individual biomarkers. These findings indicated that dual peripheral immune dysregulation in AOS was characterized by attenuated B cell trophic support and upstream IL-23/Th17 activation, and suggested that composite immune indices may provide incremental diagnostic value over single cytokines.
SN  - 2158-3188
ER  -