title: Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement.
abstract: Neuropsychiatric (NP) involvement is a poorly understood manifestation of SLE. We studied post-mortem histopathology in relation to clinical NPSLE syndromes and complement deposition in brains of NPSLE and SLE patients and controls. Furthermore, we investigated the correlation between cerebral post-mortem histopathology and ex vivo 7 T MRI findings in SLE and NPSLE.
  
  
  
  A nationwide search for autopsy material yielded brain tissue from 16 NPSLE and 18 SLE patients. Brains obtained from 24 patients who died of acute cardiac events served as controls. Apart from a histopathological evaluation, paraffin-embedded cortical tissue was stained for components of the classical, lectin and terminal complement pathways.
  
  
  
  Diffuse vasculopathy, microinfarction, macroinfarction, vasculitis and microthrombi occurred significantly more often in NPSLE than SLE patients and were absent in controls. Focal vasculopathy was found in both SLE patients and controls. Complement deposition was strongly associated with both SLE and NPSLE, but not with controls (P < 0.001). Microthrombi were found uniquely in NPSLE and were associated with C4d and C5b-9 deposits (P < 0.05). A 7 T MRI was unable to detect most small vessel injury that was visible histopathologically.
  
  
  
  Our study demonstrates that histopathological lesions in NPSLE represent a continuum, ranging from non-specific lesions such as focal vasculopathy, to more specific lesions including C4d- and C5b-9-associated microthrombi and diffuse vasculopathy related to clinical syndromes defining NPSLE. Complement deposition may be a key factor in the interaction between circulating autoantibodies and thromboischaemic lesions observed in NPSLE. Therefore, complement inhibition may have novel therapeutic potential in NPSLE.
authors.affiliation: Department of Pathology.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Cohen
authors.affiliation: Department of Pathology, E.C.Rijnink@lumc.nl.
authors.forename: Emilie C
authors.initials: EC
authors.lastname: Rijnink
authors.affiliation: Department of Radiology.
authors.forename: Rob J A
authors.initials: RJ
authors.lastname: Nabuurs
authors.affiliation: Department of Rheumatology and.
authors.forename: Gerda M
authors.initials: GM
authors.lastname: Steup-Beekman
authors.affiliation: Department of Radiology.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Versluis
authors.affiliation: Department of Radiology.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Emmer
authors.affiliation: Department of Pathology.
authors.forename: Malu
authors.initials: M
authors.lastname: Zandbergen
authors.affiliation: Department of Radiology.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Department of Rheumatology and.
authors.forename: Cornelia F
authors.initials: CF
authors.lastname: Allaart
authors.affiliation: Department of Medical Statistics & Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Wolterbeek
authors.affiliation: Department of Pathology.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.affiliation: Department of Pathology.
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: van Duinen
authors.affiliation: Department of Rheumatology and.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Pathology.
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D001344:Autopsy; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D020520:Brain Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D015935:Complement C4b / Q000276:immunology / Q000378:metabolism; D050776:Complement C5b / Q000276:immunology / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000276:immunology / Q000378:metabolism; D003171:Complement Pathway, Classical; D037582:Complement Pathway, Mannose-Binding Lectin; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020767:Intracranial Thrombosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology; D020945:Lupus Vasculitis, Central Nervous System / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D020293:Vasculitis, Central Nervous System / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000473:pathology*
chemical_list: D001323:Autoantibodies; D015938:Complement Membrane Attack Complex; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D050776:Complement C5b; D003165:Complement System Proteins
keywords: complement; histology; neuropsychiatric lupus; systemic lupus erythematosus