Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

Abstract

Background: Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.

Results: We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.

Conclusions: Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.

Figure 1

Representative histograms of CR1 measurement on blood cells. (A) CR1 measurement on erythrocytes: 1 - gated erythrocyte population. 2 - three fluorescent peaks representing non-specific (an isotype control) and specific fluorescence (schizophrenic patients and control subjects). (B) CR1 measurement on leukocytes: 1 - gated leukocyte populations. 2, 3, 4 - CR1 expression on neutrophils, monocytes, and lymphocytes, respectively.

Figure 2

The intragroup comparison (n = 117 patients, n = 142 controls) of CR1 expression (RFI) with regard to the CR1 5507 standard allele homozygotes (CC) versus G mutant allele carriers (CG+GG). The data are expressed as whisker box plots; the box represents the 25-75th percentiles, the median is indicated by a bar across the box, the whiskers on each box represent the minimum and maximum level. P = 0.0003 when comparing levels between patients and controls.