title: Humoral response against heat shock proteins and other mycobacterial antigens after intravesical treatment with bacille Calmette-Guérin (BCG) in patients with superficial bladder cancer.
abstract: Few studies have analysed the antibody response during intravesical BCG immunotherapy for superficial bladder cancer. We have examined the evolution in serum antibody response against several heat shock proteins (hsp), including the recombinant mycobacterial hsp65 and the native protein P64 from BCG, GroEL from Escherichia coli (hsp60 family), recombinant mycobacterial hsp70 and the E. coli DnaK (hsp70 family), against purified protein derivative of tuberculin (PPD) and the AG85 complex of Mycobacterium bovis BCG, as well as against tetanus toxoid in 42 patients with a superficial bladder tumour, 28 treated with six intravesical BCG instillations and 14 patients used as controls. We also analysed the lymphoproliferative response of peripheral blood mononuclear cells against PPD in this population. Data of antibody responses at 6 weeks post BCG were available in all 28 patients, and at 4 month follow up in 17 patients. All patients who demonstrated a significant increase in IgG antibodies against PPD at 4 months follow up had a significant increase already at 6 weeks of follow up. In contrast, IgG antibodies against hsp increased significantly from 6 weeks to 4 months post-treatment. A significant increase in IgG antibodies against PPD, hsp65, P64, GroEL, and hsp70 at 4 months follow up was observed in 10/17, 8/17, 10/17, 4/17 and 8/17 patients. Native P64 protein elicited a higher antibody response than recombinant mycobacterial hsp65. No increase in antibody response was observed against Dnak from E. coli, against AG85 or tetanus toxoid after BCG therapy. An increase in IgG antibodies against P64 at 4 months follow up compared with pretreatment values was found to be a significant predictor of tumour recurrence (P<0.01). Further studies with a larger number of patients are needed to confirm the value of the antibody response against P64 as a clinical independent prognostic factor.
authors.affiliation: Department of Urology, Erasme Hospital, University Clinics of Brussels, Belgium.
authors.forename: A R
authors.initials: AR
authors.lastname: Zlotta
authors.forename: A
authors.initials: A
authors.lastname: Drowart
authors.forename: K
authors.initials: K
authors.lastname: Huygen
authors.forename: J
authors.initials: J
authors.lastname: De Bruyn
authors.forename: H
authors.initials: H
authors.lastname: Shekarsarai
authors.forename: M
authors.initials: M
authors.lastname: Decock
authors.forename: M
authors.initials: M
authors.lastname: Pirson
authors.forename: F
authors.initials: F
authors.lastname: Jurion
authors.forename: K
authors.initials: K
authors.lastname: Palfliet
authors.forename: O
authors.initials: O
authors.lastname: Denis
authors.forename: F
authors.initials: F
authors.lastname: Mascart
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: C C
authors.initials: CC
authors.lastname: Schulman
authors.forename: J P
authors.initials: JP
authors.lastname: Van Vooren
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002455:Cell Division; D018834:Chaperonin 60 / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007167:Immunotherapy; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D014373:Tuberculin; C063842:dnaK protein, E coli