Baker · Annals of internal medicine 1988 · Case report with in vitro lymphocyte culture and hybridoma analysis · n=1

Seronegative Hashimoto thyroiditis with thyroid autoantibody production localized to the thyroid.

Cited 86 times in the scientific literature.

Level 4 - case-series / case-control

Single case report with in vitro laboratory characterization of patient-derived tissue.

PubMed 3337512 · doi:10.7326/0003-4819-108-1-26 · record verified 2026-08-28

What was done

A patient presenting with neck compression from a goiter and negative serologic autoimmune tests underwent thyroidectomy. Histologic analysis of the excised thyroid tissue was performed. Lymphocytes isolated from both the patient's thyroid gland and peripheral blood were transformed in vitro into lymphoblastoid cells using Epstein-Barr virus with cyclosporine. In addition, intrathyroidal lymphocytes were fused with SHM-D33 heteromyeloma cells to generate human monoclonal antibodies and assess binding to thyroid antigens.

What was found

Histology confirmed changes compatible with Hashimoto disease. Transformed intrathyroidal lymphocytes produced antibodies targeting thyroglobulin, thyroid microsomes, thyrocyte membranes, and thyrotropin, and intrathyroidal hybridomas produced antibodies with high-affinity binding specific to thyroid antigens. Transformed peripheral blood lymphocytes showed no antithyroid activity. The abstract reported no numerical titers, percentages, or binding constants.

Why it matters

This study provides mechanistic evidence that Hashimoto thyroiditis can occur as an organ-restricted autoimmune process without circulating autoantibodies, explaining how seronegative patients can still have histologically active disease.

Limits

The study is limited to a single patient (n = 1), precluding any estimate of how frequently isolated intrathyroidal autoimmunity occurs. Measurements relied on in vitro transformation and hybridoma culture rather than direct quantification of in situ antibody levels. No numerical values or confidence intervals were provided in the abstract.

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