Biological activity of lymphocytotoxic antibodies in Graves’ disease and Hashimoto’s thyroiditis

Abstract
Sera of 48 patients with Graves’ disease (GD) and 23 with Hashimoto’s thyroiditis (HT) were tested for lymphocytotoxic (LCT), granulocytotoxic (GCT) and monocytotoxic (MCT) activity. In GD, 12 patients (25%) had cold-reacting LCT and 13 patients (27%) had warm-reacting LCT. LCT were cytotoxic to both B and T cells but the majority of sera with cold-reacting LCT and eluates from lymphocytes were more cytotoxic to B lymphocytes. Warm-reacting LCT were directed exclusively against B cells. LCT did not correlate with peripheral lymphocyte counts, antithyroglobulin or antimicrosomal antibodies, sex, age, pregnancies, thyroid status or medication. However the mean duration of the disease was 15 months in LCT positive group and 55 months in LCT negative group (p < 0.01). Weak GCT were found in 8 of 35 sera (23%). Six of 33 sera (18%) contained cold-reacting MCT and 9 (27%) had warm-reacting MCT. Some cytotoxins were directed against several types of cells as evidenced by cytotoxicity of eluates from lymphocytes against PMN and/or monocytes. Of 23 patients with HT, 11 (48%) had cold-reacting LCT. None had warm-reacting LCT. Sera and eluates from lymphocytes showed predominant cytotoxicity toward B cells. No correlation to the presence of antibodies, sex, age, pregnancies, thyroid status or medication was detected. Four of 23 sera had weak cold-reacting GCT, 5 had cold-reacting MCT which killed on average 31 % of monocytes and 4 had weak warm-reacting MCT. Twelve of 22 sera from GD and HT had cytotoxic activity against thyroid cells (TCT). TCT correlated with LCT at p < 0.05. Eluates from lymphocytes had TCT activity but the supernatants devoid of LCT activity retained TCT as well. Thus the identity of LCT and TCT cannot be proven at the present time. None of 4 tested sera reacted with glycolipids. Although the clinical significance of cytotoxins is unknown, their presence in the early stages of GD may mean that their production is altered by either the natural course of the disease or by therapy. Cytotoxins should be taken into consideration while investigating immunologic abnormalities in thyroid diseases.