T cells and autoantibodies to human HSP70 in type 1 diabetes in children.
We studied T-cell proliferative responses (stimulation index: SI) and autoantibodies to human HSP60, HSP70 and HSP90 proteins in 25 children (mean age 10.1+/-3.8 years) newly diagnosed with Type 1 diabetes. The control group for T cells included 25 adults and three pediatric donors without Type 1 diabetes. Controls for antibodies included 10 pediatric subjects. The T-cell responses to HSP70 of the test group (mean SI=4.5+/-3.1) were significantly greater than those of the control group (meanSI=1.4+/-0.6; p<0.0001); the incidence of HSP70 responders was (85%) compared to 14% in the control group. All but three of the Type 1 children who responded to HSP70 also responded to HSP60 (85%). The T-cell responses of the Type 1 group to HSP90 (mean SI=1.7+/-1.1) were similar to those of the control group (mean SI=1.5+/-0.7). We mapped HSP70 epitopes recognized by T cells in seven subjects using overlapping peptides of the molecule. Among the Type 1 subjects, IgG seropositivity was 45% to HSP60, 30% to HSP70, and 15% to HSP90. Thus, we conclude that children with newly diagnosed Type 1 diabetes manifest heightened T-cell autoimmunity to HSP70 and HSP60, but not to HSP90.
Abulafia-Lapid
Rivka
R
HBRC Department of Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Ein-Karem, Jerusalem, Israel. rivka_abulafia@yahoo.com
Gillis
David
D
Yosef
Orit
O
Atlan
Henri
H
Cohen
Irun R
IR
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000235:genetics; D016022:Case-Control Studies; D018834:Chaperonin 60 / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D007074:Immunoglobulin G