title: LTT-MELISA is clinically relevant for detecting and monitoring metal sensitivity.
abstract: OBJECTIVE
  Chronic low-level metal exposure may result in metal sensitization and undesirable side-effects. The main sources of metal exposure are from the environment or from corrosion of dental metal alloys. Affected patients are routinely diagnosed with the epicutaneous (patch) test. However, such testing may induce false-positive (irritative) reactions and may in itself sensitize or exacerbate symptoms. Alternatively, MELISA (Memory Lymphocyte ImmunoStimulation Assay), an optimized lymphocyte transformation test (LTT), can be used. In this study we analyzed the overall frequency and distribution of metal sensitization among symptomatic, metal-exposed patients. In addition, we determined the reproducibility of the assay and assessed its clinical relevance for detecting and monitoring hypersensitivity to metals.
  
  
  METHODS
  To analyze the frequency and distribution of metal sensitization, blood from 700 consecutive patients was tested against a total of 26 metals in the validated LTT-MELISA. For reproducibility testing, 391 single metal tests from 63 patients were performed in parallel. Finally, to assess clinical relevance, 14 patients with known metal exposure showing local (dry mouth, Oral Lichen Planus, Burning Mouth Syndrome, eczema) and/or systemic (chronic infections, fatigue, autoimmune disorders, central nervous system disturbances, depression) effects were tested in LTT-MELISA. In 7 cases testing was repeated following removal of the allergy-causing metals or, in 2 additional cases, without therapeutic intervention.
  
  
  RESULTS
  Of the 700 patients tested, 74.6% responded to >/= 1 metal in LTT-MELISA, with a subgroup of 17.9% responding to >/= 3 metals. Reactivity was most frequent to nickel (68.2%), followed by cadmium (23.7%), gold (17.8%), palladium (12.7%), inorganic mercury (11.4%), molybdenum (10.8%), beryllium (9.7%), titanium dioxide (4.2%), lead (3.7%), and platinum (3.4%). Reproducibility was 94.9%, with most discordant results in a low-positive range. Removal of the alloys or prostheses containing allergenic metals resulted in remarkable clinical improvement correlating with a significant reduction or complete normalization of specific lymphocyte reactivity. In contrast, both LTT-MELISA reactivity and clinical symptoms remained unchanged in follow-up samples from the 2 patients who did not remove the source of metal exposure.
  
  
  CONCLUSIONS
  The optimized LTT-MELISA test is a clinically useful and reliable tool for identifying and monitoring metal sensitization in symptomatic metal-exposed individuals.
authors.affiliation: Laboratory Center Bremen, Bremen, Germany. evt@laborzentrum-bremen.de.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Valentine-Thon
authors.forename: Kurt
authors.initials: K
authors.lastname: Müller
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Guzzi
authors.forename: Sybille
authors.initials: S
authors.lastname: Kreisel
authors.forename: Peter
authors.initials: P
authors.lastname: Ohnsorge
authors.forename: Martin
authors.initials: M
authors.lastname: Sandkamp
mesh_terms: D000328:Adult; D000368:Aged; D003723:Dental Amalgam / Q000633:toxicity; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy; D007118:Immunoassay / Q000379:methods*; D008213:Lymphocyte Activation; D008670:Metals / Q000633:toxicity*; D008875:Middle Aged; D016273:Occupational Exposure; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D008670:Metals; D003723:Dental Amalgam