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

Abstract

BackgroundWhereas 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.ResultsWe 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.ConclusionsOur 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.

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling

“…Genetic studies of the complement pathway in schizophrenia reveal disease-associations of the C1QB gene, complement control-related genes, and complement surface receptor gene CD46 (Havik et al, 2011; Zakharyan et al, 2011). In multiple reports, elevated levels of complement-containing circulating immune complexes were found in individuals with schizophrenia compared to controls (Arakelyan et al, 2011; Boyajyan et al, 2008; Mailian et al, 2005; Mayilyan et al, 2008; Severance et al, 2012b; Vetlugina et al, 1984). This complement activity can be triggered by exposure to gluten and casein.…”

Maternal complement C1q and increased odds for psychosis in adult offspring

“…In our studies of schizophrenia, we have linked elevated C1q to the presence of IgG antibodies directed against milk caseins and wheat glutens (Severance et al, 2012b), and to inflammatory gut processes in experimental animal models (Severance et al, 2012c). Numerous other accounts also report complement system physiological and genetic aberrations in schizophrenia (Arakelyan et al, 2011; Boyajyan et al, 2008; Havik et al, 2011; Mailian et al, 2005; Mayilyan et al, 2008; Vetlugina et al, 1984; Zakharyan et al, 2011). …”

Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia

“…Complement pathway activation may occur at increased rates in schizophrenia, and elevated levels of circulating immune complexes containing C1q have been found in individuals with schizophrenia compared to controls (Arakelyan et al, 2011; Boyajyan et al, 2008; Mailian et al, 2005; Mayilyan et al, 2008; Vetlugina et al, 1984). Complement factor C3 proteins were also found to be a part of these complexes, but the antigenic protein initiating the immune response was not identified (Arakelyan et al, 2011).…”

“…Complement factor C3 proteins were also found to be a part of these complexes, but the antigenic protein initiating the immune response was not identified (Arakelyan et al, 2011). Food sensitivities to bovine milk caseins and wheat glutens, as evident by antibody-based measures, have been reported in a number of studies of schizophrenia over the years (Cascella et al, 2011; Dickerson et al, 2010b; Dohan, 1981; Dohan et al, 1972; Karlsson et al, 2012; Niebuhr et al, 2011; Reichelt and Landmark, 1995; Samaroo et al, 2010; Severance et al, 2010a), an indication that these foods might be possible antigenic candidates for C1q binding.…”