title: Systemic inflammation in acute intermittent porphyria: a case-control study.
abstract: This study aimed to examine whether acute intermittent porphyria (AIP) is associated with systemic inflammation and whether the inflammation correlates with disease activity. A case-control study with 50 AIP cases and age-, sex- and place of residence-matched controls was performed. Plasma cytokines, insulin and C-peptide were analysed after an overnight fast using multiplex assay. Long pentraxin-3 (PTX3) and complement activation products (C3bc and TCC) were analysed using enzyme-linked immunosorbent assay (ELISA). Urine porphobilinogen ratio (U-PBG, µmol/mmol creatinine), haematological and biochemical tests were performed using routine methods. Questionnaires were used to register AIP symptoms, medication and other diseases. All 27 cytokines, chemokines and growth factors investigated were increased significantly in symptomatic AIP cases compared with controls (P < 0·0004). Hierarchical cluster analyses revealed a cluster with high visfatin levels and several highly expressed cytokines including interleukin (IL)-17, suggesting a T helper type 17 (Th17) inflammatory response in a group of AIP cases. C3bc (P = 0·002) and serum immunoglobulin (Ig)G levels (P = 0·03) were increased significantly in cases with AIP. The U-PBG ratio correlated positively with PTX3 (r = 0·38, P = 0·006), and with terminal complement complex (TCC) levels (r = 0·33, P = 0·02). PTX3 was a significant predictor of the biochemical disease activity marker U-PBG in AIP cases after adjustment for potential confounders in multiple linear regression analyses (P = 0·032). Prealbumin, C-peptide, insulin and kidney function were all decreased in the symptomatic AIP cases, but not in the asymptomatic cases. These results indicate that AIP is associated with systemic inflammation. Decreased C-peptide levels in symptomatic AIP cases indicate that reduced insulin release is associated with enhanced disease activity and reduced kidney function.
authors.affiliation: Department of Laboratory Medicine, Nordland Hospital, Bodø, Norway.|Institute of Clinical Medicine, K.G. Jebsen TREC, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Storjord
authors.affiliation: Department of Laboratory Medicine, Nordland Hospital, Bodø, Norway.
authors.forename: J A
authors.initials: JA
authors.lastname: Dahl
authors.affiliation: Institute of Clinical Medicine, K.G. Jebsen TREC, UiT The Arctic University of Norway, Tromsø, Norway.|Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Landsem
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Fure
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: J K
authors.initials: JK
authors.lastname: Ludviksen
authors.affiliation: Department of Obstetrics and Gynecology, UiT The Arctic University of Norway, Tromsø, Norway.|Department of Research, Nordland Hospital, Bodø, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Goldbeck-Wood
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: B O
authors.initials: BO
authors.lastname: Karlsen
authors.affiliation: Department of Anesthesiology, Nordland Hospital, Bodø, Norway.
authors.forename: K S
authors.initials: KS
authors.lastname: Berg
authors.affiliation: Institute of Clinical Medicine, K.G. Jebsen TREC, UiT The Arctic University of Norway, Tromsø, Norway.|Research Laboratory, Nordland Hospital, Bodø, Norway.|Department of Immunology, Oslo University Hospital, and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.|Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Institute of Clinical Medicine, K.G. Jebsen TREC, UiT The Arctic University of Norway, Tromsø, Norway.|Department of Anesthesiology, Nordland Hospital, Bodø, Norway.|Nord University, Bodø, Norway.
authors.forename: E
authors.initials: E
authors.lastname: W Nielsen
authors.affiliation: Department of Laboratory Medicine, Nordland Hospital, Bodø, Norway.|Institute of Clinical Medicine, K.G. Jebsen TREC, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: O-L
authors.initials: OL
authors.lastname: Brekke
mesh_terms: D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017118:Porphyria, Acute Intermittent / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D011228:Prealbumin / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D016207:Cytokines; D007074:Immunoglobulin G; D007328:Insulin; D011228:Prealbumin
keywords: chemokines; complement; cytokines; human; inflammation