title: Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease.
abstract: BACKGROUND
  Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD.
  
  
  METHODS
  Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögren's syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA(®) (Memory Lymphocyte Immuno Stimulation Assay).
  
  
  RESULTS
  In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P<0.0001). The most frequent allergens were nickel, mercury, gold and palladium.
  
  
  CONCLUSIONS
  Patients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies.
authors: Wenner-Gren Institute for Experimental Biology, University of Stockholm, Stockholm, Sweden. Electronic address: vera@melisa.org.
authors: Vera
authors: V
authors: Stejskal
authors: Chemical Pathology, Burton Hospitals NHS Foundation Trust, Burton upon Trent, United Kingdom.
authors: Tim
authors: T
authors: Reynolds
authors: Council for Nutritional and Environmental Medicine, Mo i Rana, Norway.
authors: Geir
authors: G
authors: Bjørklund
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016022:Case-Control Studies; D003793:Dental Restoration, Permanent / Q000009:adverse effects* / Q000295:instrumentation; D005260:Female; D006046:Gold / Q000276:immunology / Q000633:toxicity; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000453:epidemiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008628:Mercury / Q000276:immunology / Q000633:toxicity; D008670:Metals / Q000276:immunology / Q000633:toxicity*; D008875:Middle Aged; D009532:Nickel / Q000276:immunology / Q000633:toxicity; D010165:Palladium / Q000276:immunology / Q000633:toxicity; D012859:Sjogren's Syndrome / Q000276:immunology*; D014025:Titanium / Q000276:immunology / Q000633:toxicity; D055815:Young Adult
chemical_list: D008670:Metals; D010165:Palladium; D006046:Gold; D009532:Nickel; D014025:Titanium; D008628:Mercury
keywords: Delayed type hypersensitivity; Metal allergy; Rheumatoid arthritis; Sjögren's syndrome; Systemic lupus erythematosus