Complement C4 gene copy numbers modulate serum immune protein profiles in patients with first-episode psychosis and healthy controls in a sex-specific manner

Thumbnail Image

Files

Complement_C4_gene_copy_numbers_modulate_serum_immune_protein_profiles_in_patients_with_first-episode_psychosis_and_healthy_controls_in_a_sex-specific_manner.pdf (3.05 MB)

Access rights

openAccess
CC BY
publishedVersion

URL

Journal Title

Journal ISSN

Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
This publication is imported from Aalto University research portal.
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Unless otherwise stated, all rights belong to the author. You may download, display and print this publication for Your own personal use. Commercial use is prohibited.

Authors

Date

2025-11

Department

Department of Computer Science

Major/Subject

Mcode

Degree programme

Language

en

Pages

9

Series

Schizophrenia Research, Volume 285, pp. 330-338

Abstract

The copy number of complement component C4 genes (C4A and C4B) has been associated with schizophrenia risk, particularly in men. Psychotic disorders are associated with alterations in serum immune protein levels, but whether the C4A/B copy numbers are related to circulating immune protein levels is not known. Two Finnish first-episode psychosis (FEP) cohorts were studied, comprising 105 FEP patients and 71 controls who were assessed at baseline and at two-month and one-year follow-ups. The C4A/B copy numbers were analyzed by genomic RT-PCR. We measured immune protein concentrations using a 38-plex Luminex assay at all available time points and correlated the results with the C4A/B copy numbers using Spearman's rank correlations. The median C4A and C4B copy numbers did not differ between patients and controls. C4A copy number correlated broadly and positively with serum cytokine and chemokine levels across all measurement points in FEP patients, while correlations with C4B copy numbers were negative. Correlations in controls were weaker and less consistent. When analyzed separately in males and females, the broadest and most significant positive correlations of immune protein levels with C4A copy number and negative correlations with C4B copy number were observed in male FEP patients. C4A and C4B gene copy variations influence immunoinflammatory responses and serum levels of many immune proteins. This phenomenon was pronounced in male FEP patients, suggesting that they may be more vulnerable to tissue injury or infections. The results underscore the importance of investigating sex-specific effects of C4 gene variations in psychotic disorders.

Description

Publisher Copyright: © 2025 The Authors.

Keywords

Chemokines, Complement C4 gene copy number, Cytokines, First-episode psychosis, Immune proteins, Sex

Other note

DOI

10.1016/j.schres.2025.10.001

Citation

Rankka, U, Lokki, M L, Vahermaa, V, Laurikainen, H, Hietala, J, Honkanen, J, Meri, S & Suvisaari, J 2025, 'Complement C4 gene copy numbers modulate serum immune protein profiles in patients with first-episode psychosis and healthy controls in a sex-specific manner', Schizophrenia Research, vol. 285, pp. 330-338. https://doi.org/10.1016/j.schres.2025.10.001

Permanent link to this item

https://urn.fi/URN:NBN:fi:aalto-202511058694

Collections

[article-cris] Perustieteiden korkeakoulu / SCI