Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes.
Markedly elevated levels of serum IL-4 were reported previously in 50% of a small group of type 1 diabetes nonprogessors. To determine the patterns of expression for this phenotype, a larger cohort of 58 families containing type 1 diabetic patients was examined. Analysis of the two-site ELISA assay used to measure serum IL-4 revealed evidence for heterophile antibodies, i.e., nonanalyte substances in serum capable of binding antibodies mutivalently and providing erroneous analyte (e.g., IL-4) quantification. Interestingly, relatives without type 1 diabetes were significantly more likely to have this phenotype than were patients with the disease (P = 0.003). In addition, the trait appears to have clustered within certain families and was associated with the protective MHC allele DQB1*0602 (P = 0.008). These results suggest that heterophile antibodies represent an in vivo trait associated with self-tolerance and nonprogression to diabetes.
Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
J X
JX
She
T M
TM
Ellis
S B
SB
Wilson
C H
CH
Wasserfall
M
M
Marron
S
S
Reimsneider
S C
SC
Kent
D A
DA
Hafler
D S
DS
Neuberg
A
A
Muir
J L
JL
Strominger
M A
MA
Atkinson
D000483:Alleles; D000910:Antibodies, Heterophile / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D015847:Interleukin-4 / Q000097:blood*; D008285:Major Histocompatibility Complex; D010641:Phenotype
D000910:Antibodies, Heterophile; D016207:Cytokines; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D015847:Interleukin-4