title: Changes in GAD65Ab-specific antiidiotypic antibody levels correlate with changes in C-peptide levels and progression to islet cell autoimmunity.
abstract: BACKGROUND
  The previously reported absence of 65-kDa glutamate decarboxylase antibody (GAD65Ab)-specific antiidiotypic antibodies (anti-Id) in type 1 diabetes (T1D) patients at clinical onset could be due to an inability to mount an antibody response to GAD65Ab or a longitudinal decline in anti-Id levels.
  
  
  OBJECTIVE
  We investigated anti-Id levels in longitudinal samples obtained from T1D patients (n = 41) (clinical diagnosis - 12 months), and latent autoimmune diabetes in adults (LADA) patients (n = 32) who received alum-formulated human recombinant GAD65 (baseline - 12 months). We also determined anti-Id levels in a small cohort of Type 2 diabetes patients during their development of autoimmune T cell responses.
  
  
  RESULTS
  At clinical onset T1D patients presented no or low anti-Id levels. However, 22/41 T1D patients showed ≥50% increase in GAD65Ab-specific anti-Id levels during follow-up; peaking at 3 (n = 1), 6 (n = 10), 9 (n = 10), or 12 (n = 1) months. Increasing anti-Id levels marked patients who experienced a temporary increase in C-peptide levels. Anti-Id levels correlated significantly with glycated hemoglobin and C-peptide levels at 6 and 9 months (P values ranged from <0.001 to <0.05). In LADA patients receiving placebo, anti-Id levels declined in seven of nine patients, whereas four of five patients receiving 20 μg alum-formulated human recombinant GAD65 showed increasing anti-Id levels. Changes in anti-Id and C-peptide levels closely correlated (P < 0.0001). The significant decline in anti-Id levels (P = 0.03) in T2D patients developing T cell autoimmune responses supports our hypothesis that declining anti-Id levels are associated with developing islet autoimmunity.
  
  
  CONCLUSIONS
  The close association between GAD65Ab-specific anti-Id levels and β-cell function may provide a novel marker for the progression of autoimmune diabetes.
authors.affiliation: Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Ortqvist
authors.forename: B
authors.initials: B
authors.lastname: Brooks-Worrell
authors.forename: K
authors.initials: K
authors.lastname: Lynch
authors.forename: J
authors.initials: J
authors.lastname: Radtke
authors.forename: L M
authors.initials: LM
authors.lastname: Bekris
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: C-D
authors.initials: CD
authors.lastname: Agardh
authors.forename: C M
authors.initials: CM
authors.lastname: Cilio
authors.forename: A L
authors.initials: AL
authors.lastname: Lethagen
authors.forename: B
authors.initials: B
authors.lastname: Persson
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
authors.forename: J
authors.initials: J
authors.lastname: Reichow
authors.forename: S
authors.initials: S
authors.lastname: Oak
authors.forename: J P
authors.initials: JP
authors.lastname: Palmer
authors.forename: C S
authors.initials: CS
authors.lastname: Hampe
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D002096:C-Peptide / Q000097:blood* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood* / Q000276:immunology; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D011446:Prospective Studies
chemical_list: D000888:Antibodies, Anti-Idiotypic; D002096:C-Peptide; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2