THYROID PEROXIDASE AUTOANTIBODY FINGERPRINTS .2. A LONGITUDINAL-STUDYIN POSTPARTUM THYROIDITIS

It is not known whether epitopes recognized by autoantibodies in an in dividual remain constant or change over time, especially during pertur bations of the humoral immune response. To address this question, we s tudied the epitopic profile (''fingerprint'') of autoantibodies to thy roid peroxidase (TPO) in the sera of 19 women during the postpartum pe riod. Fingerprints were determined in competition studies using 4 reco mbinant F(ab). At delivery and at 3 time intervals over the subsequent 9-12 months, the pool of F(ab) inhibited autoantibody binding to TPO by 80-100%, consistent with the definition by these F(ab) of a TPO imm unodominant region (A1, A2, B1, and B2 domains). Despite a nide spectr um among individuals, the TPO epitopic fingerprints for all 19 women w ere relatively unchanged throughout the postpartum period. Fingerprint constancy occurred regardless of fluctuations in serum TPO autoantibo dy levels. When assessed numerically as a ratio of inhibition by the A domain F(ab) to inhibition by the B domain F(ab), the A/B domain rati os in individual women ranged from 0.2 (predominantly B domain) to mor e than 3.0 (predominantly A domain). However, for each individual woma n, the A/B epitopic ratio was conserved throughout the study interval. Our TPO autoantibody epitopic fingerprint data have potential implica tions for understanding the humoral autoimmune response in man. First, the present study indicates a remarkable lack of spreading of B cell epitopes during a state of perturbation of the immune system over a pe riod of 1 yr. Second, and perhaps more important, despite marked varia tions in TPO epitopic profiles among different individuals, their cons tancy over time suggests that TPO autoantibody fingerprints may be inh erited.