title: Measurement of immunofunctional leptin to detect and monitor patients with functional leptin deficiency.
abstract: OBJECTIVE
  Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool to detect functional leptin deficiency.
  
  
  METHODS
  An immunoassay capable of recognizing the functionally relevant receptor-binding complex with leptin was developed (bioLep). The analytical quality of bioLep was validated and compared to a conventional assay for immune-reactive leptin (irLep). Its clinical relevance was evaluated in a cohort of lean and obese children and adults as well as in children diagnosed with functional leptin deficiency and their parents.
  
  
  RESULTS
  In the clinical cohort, a bioLep/irLep ratio of 1.07 (range: 0.80-1.41) was observed. Serum of patients with non-functional leptin due to homozygous amino acid exchanges (D100Y or N103K) revealed high irLep but non-detectable bioLep levels. Upon treatment of these patients with metreleptin, irLep levels decreased, whereas levels of bioLep increased continuously. In patient relatives with heterozygous amino acid exchanges, a bioLep/irLep ratio of 0.52 (range: 0.48-0.55) being distinct from normal was observed.
  
  
  CONCLUSIONS
  The new bioLep assay is able to diagnose impaired leptin bioactivity in severely obese patients with a homozygous gene defect and in heterozygous carriers of such mutations. The assay serves as a diagnostic tool to monitor leptin bioactivity during treatment of these patients.
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Mediagnost GmbHReutlingen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Pridzun
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ranke
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: von Schnurbein
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Moss
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brandt
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kohlsdorf
authors.affiliation: Institute of Pharmacology and ToxicologyUniversity Medical Center Ulm, Ulm, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Moepps
authors.affiliation: Institute of Laboratory MedicineClinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaab
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Jan-Bernd
authors.initials: JB
authors.lastname: Funcke
authors.affiliation: Institute of Pharmacology and ToxicologyUniversity Medical Center Ulm, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Gierschik
authors.affiliation: Division of Pediatric Endocrinology and DiabetesDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.affiliation: Mediagnost GmbHReutlingen, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Flehmig
authors.affiliation: Institute of Laboratory MedicineClinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D020738:Leptin / Q000097:blood* / Q000172:deficiency*; D008297:Male
chemical_list: D020738:Leptin