title: Complement Receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function.
abstract: Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on C3 activation. Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing-remitting MS (n=33; 6.2ng/mL) and secondary-progressive MS (n=9; 7.0ng/mL) as compared to controls (n=18; 4.1ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of C3b to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3. These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions.
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden; Department of Cardiothoracic Surgery and Anaesthesia, Uppsala University Hospital, Sweden; Department of Surgical Sciences, Uppsala University, Sweden. Electronic address: rickard.lindblom@ki.se.
authors.forename: Rickard P F
authors.initials: RP
authors.lastname: Lindblom
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden.
authors.forename: Shahin
authors.initials: S
authors.lastname: Aeinehband
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Ström
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden.
authors.forename: Faiez
authors.initials: F
authors.lastname: Al Nimer
authors.affiliation: Linnæus Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sandholm
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden; Linnæus Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
mesh_terms: D000328:Adult; D003167:Complement Activation / Q000276:immunology; D015922:Complement C1q / Q000134:cerebrospinal fluid / Q000276:immunology; D003176:Complement C3 / Q000134:cerebrospinal fluid / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D017464:Receptors, Complement 3d / Q000276:immunology*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D003176:Complement C3; D017464:Receptors, Complement 3d; D015922:Complement C1q
keywords: Complement Receptor 2; Complement system; Multiple sclerosis; Neurodegeneration; Neuroinflammation