title: Serum antibodies against CD28-- a new potential marker of dismal prognosis in melanoma patients.
abstract: BACKGROUND
  Autoantibodies against CD28 have been found in patients with autoimmune and atopic diseases. These antibodies may act as superagonists and activate T cells but may also be antagonistic or induce immunosuppressive effects by activating regulatory T cells. Autoimmunity in melanoma patients has been discussed controversially.
  
  
  OBJECTIVE
  We investigated 230 melanoma patients for the occurrence of CD28 antibodies and the effect of the latter on overall and progress-free survival.
  
  
  METHODS
  We constructed an ELISA assay to measure CD28 serum antibodies. 230 patients with melanoma and a control-group of 625 patients consistent of 212 patients with virus hepatitis b or c, 149 patients with allergies, 78 patients with psoriasis, 46 patients with plasmocytoma and 140 healthy blood donors were investigated for the occurrence of CD28 antibodies.
  
  
  RESULTS
  CD28 abs occur at a higher percentage in patients with melanoma and in patients with viral hepatitis than in other groups investigated (p<0.001). Occurrence of CD28 abs is significantly higher in patients receiving interferons independent from the underlying disease (p<0.001). In vitro CD28 serum antibodies have an inhibitory effect on the CD28 receptor as they lead to reduced stimulation of Jurkat cells. Presence of CD28 was correlated with a higher risk of dying from melanoma (p = 0.043), but not with a significantly shortened overall survival or progression-free survival.
  
  
  CONCLUSIONS
  Interferon therapy appears to induce the production of CD28 abs. In light of reports that these CD28 abs induce immunosuppressive Tregs and - as our data show - that they are inhibitors of CD28 receptor mediated stimulation, the continuation of therapies with interferons in melanoma patients developing CD28 antibodies should be critically reconsidered, since our data indicate a worse outcome of patients with CD28 abs.
authors.affiliation: Department of Dermatology, Saarland University Hospital, Homburg/Saar, Germany. rebecca.koerner@uks.eu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Körner
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Preuss
authors.forename: Natalie
authors.initials: N
authors.lastname: Fadle
authors.forename: Darius
authors.initials: D
authors.lastname: Madjidi
authors.forename: Frank
authors.initials: F
authors.lastname: Neumann
authors.forename: Lennart
authors.initials: L
authors.lastname: Bergeler
authors.forename: Stefan
authors.initials: S
authors.lastname: Gräber
authors.forename: Cornelia S L
authors.initials: CS
authors.lastname: Müller
authors.forename: Frank
authors.initials: F
authors.lastname: Grünhage
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.forename: Claudia
authors.initials: C
authors.lastname: Pföhler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018106:CD28 Antigens / Q000097:blood / Q000276:immunology*; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057809:HEK293 Cells; D006505:Hepatitis / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D019169:Jurkat Cells; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000276:immunology*; D008875:Middle Aged; D011379:Prognosis; D011994:Recombinant Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000097:blood* / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D018106:CD28 Antigens; D011994:Recombinant Proteins; D007372:Interferons; D013954:Thyroglobulin