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Analysis of Immunoglobulin G Antithyroid Peroxidase Antibodies from Different Tissues in Hashimoto’s Thyroiditis¹

Department of Medicine, University of Sheffield Clinical Sciences Center, Northern General Hospital (R.S.M., M.S.A., E.H.K., P.F.W., A.P.W.), Sheffield, United Kingdom S5 7AU; the Department of Biochemistry, Medical Center of Postgraduate Education (A.G.), Warsaw 01 813, Poland; and the Department of Medicine, Kings College School of Medicine (J.P.B.), Denmark Hill, London, United Kingdom SE5 8RX

Address all correspondence and requests for reprints to: Prof. A. P. Weetman, Department of Medicine, University of Sheffield Clinical Sciences Center, Northern General Hospital, Sheffield, United Kingdom S5 7AU.

Antibodies (Ab) to thyroid peroxidase (TPO) are common in patients with autoimmune thyroid disease and may play a role in disease pathogenesis. We have prepared immunoglobulin G (IgG) and IgG phage display combinatorial libraries from the cervical (thyroid-draining) lymph nodes of 2 Hashimoto’s thyroiditis patients and from the thyroid of 1 patient. After selection with purified recombinant human TPO, up to 10 high affinity IgG clones from each tissue source were analyzed further. No IgG Fab were detected in the patient with the highest TPO Ab titer. Sequence analysis of the clones showed restricted heavy and light chain usage, similar to that in previously published TPO-reactive Fabs. This was despite the substantially larger sizes of the initial libraries, the use of lymph node tissue to generate libraries, and the analysis of the repertoire in patients with Hashimoto’s thyroiditis rather than Graves’ disease. There was overall similarity in sequences obtained from lymph node and thyroid libraries, with higher levels of somatic hypermutation in the former. The Fab inhibited binding of serum TPO Ab from five patients by 55–95%. These data together with those from previous reports indicate that although there is no unique Ab gene usage, there is the recurrent presence of certain variable regions in the high affinity TPO Ab response.

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