title: Autoantibodies against 21-hydroxylase and side-chain cleavage enzyme in autoimmune Addison's disease are mainly immunoglobulin G1.
abstract: OBJECTIVE
  Immunoglobulin G (IgG) antibodies to the steroidogenic enzymes 21-hydroxylase (21OH) and side-chain cleavage enzyme (SCC) are important diagnostic markers for autoimmune Addison's disease and autoimmune polyendocrine syndromes (APS) types I and II. The characterization of autoantibody (IgG) subclasses may reveal information on how tIssue destruction takes place; therefore, IgG subtypes of anti-21OH and anti-SCC antibodies from sera of patients with Addison's disease, APS I and APS II were determined using recombinant 21OH and SCC.
  
  
  METHODS
  SCC(51-521) and his-SCC(51-521) were expressed by pET-scc in the Escherichia coli strain BL21 Star (DE3) and inclusion bodies were purified. Full-length, human 21OH fused to an N-terminal 6x histidine affinity tag was expressed in insect cells by using the baculovirus expression system bac-to-bac. Western blots were used to investigate the IgG subtype(s) of the autoantibodies against 21OH and SCC in patients and healthy blood donors.
  
  
  RESULTS
  All anti-SCC positive sera (n=10) contained autoantibodies of the IgG1 subclass, while four out of ten also contained IgG3. All anti-21OH positive sera (n=16) had autoantibodies exclusively against IgG1. Sera from 20 healthy subjects did not show any reactivity against 21OH or SCC.
  
  
  CONCLUSIONS
  The finding of a predominating IgG1 response against 21OH and SCC may suggest that T helper (Th) cells of the Th1 subclass are involved in destruction of the adrenal cortex in patients with autoimmune Addison's disease.
authors.affiliation: Division of Endocrinology, Institute of Medicine, Haukeland University Hospital, N-5021, Bergen, Norway. Anette.Boe@med.uib.no
authors.forename: Anette S
authors.initials: AS
authors.lastname: Bøe
authors.forename: Geir
authors.initials: G
authors.lastname: Bredholt
authors.forename: Per M
authors.initials: PM
authors.lastname: Knappskog
authors.forename: Trond Ove
authors.initials: TO
authors.lastname: Hjelmervik
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
mesh_terms: D000224:Addison Disease / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D013255:Steroid 21-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme