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l-ficolin-MASP arm of the complement system in schizophrenia.

Karine R Mayilyan1, Anders Krarup2, Armen F Soghoyan3

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Schizophrenia (SZ) may involve alterations in the lectin pathway, specifically with increased levels of l-ficolin and MASP-2 (mannose-binding lectin-associated serine protease 2) in patients. These changes correlate with disease type and complement activity, suggesting a role in SZ pathophysiology.

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CRPComplement systemGender dichotomyLectin pathway activityMASP-2Schizophrenial-ficolin

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Area of Science:

  • Immunology
  • Neuroscience
  • Genetics

Background:

  • Schizophrenia (SZ) etiology is linked to abnormal neurodevelopment influenced by in utero adversities.
  • The lectin complement pathway, involving MBL-associated serine proteases (MASP), plays a role in neuronal development.
  • Previous studies implicated MBL-MASP complexes in SZ; this study investigates the l-ficolin-MASP arm.

Purpose of the Study:

  • To investigate serum l-ficolin and plasma MASP-2 levels and activity in chronic schizophrenic patients.
  • To explore the association of these complement components with SZ pathophysiology and clinical variables.
  • To examine correlations between lectin pathway components and other complement system activities.

Main Methods:

  • Measured serum l-ficolin and plasma MASP-2 concentrations in SZ patients and controls.
  • Assessed the activity of l-ficolin-bound MASP-2.
  • Analyzed complement-related variables, including classical and alternative pathway activities.
  • Correlated complement levels and activities with demographic data and SZ subtypes.

Main Results:

  • Schizophrenia patients exhibited significantly higher serum l-ficolin levels (~40% increase) compared to controls.
  • MASP-2 plasma concentration showed significant gender-dependent variability, with higher levels in female patients.
  • Increased l-ficolin-bound MASP-2 activity was observed in schizophrenia patients.
  • L-ficolin and MASP-2 levels were associated with schizophrenia type (paranoid SZ had higher l-ficolin, lower MASP-2).
  • Correlations were found between lectin pathway components and classical/alternative pathway activities, C2 activity, and C-reactive protein (CRP).

Conclusions:

  • The findings indicate alterations in the l-ficolin-related lectin pathway in schizophrenia pathophysiology.
  • These alterations involve changes in l-ficolin and MASP-2 protein concentration and activity levels.
  • The lectin pathway, beyond MBL-MASP, appears to be involved in SZ, potentially contributing to neurodevelopmental abnormalities.