HODGKINS-DISEASE TREATED WITH NECK RADIATION IS ASSOCIATED WITH INCREASED ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY AGAINST HUMAN EXTRAOCULAR-MUSCLE CELLS

Patients with Hodgkin's disease have higher a prevalence of thyroid fu nction abnormalities and, perhaps, orbitopathy than the general popula tion, but the pathophysiology of this association and its relationship to Hodgkin's disease treatment remain unclear. We analyzed the freque ncy of thyroid function abnormalities, autoantibodies against thyroid antigens, and autoimmunity against extraocular muscle cell antigens by Western blot analyses and antibody-dependent cellular cytotoxicity (A DCC) assays in patients with Hodgkin's disease (n=20) and controls (n= 10). Hodgkin's disease patients were subdivided into those treated wit h thyroidal external beam radiation therapy (XRT, n=15) or chemotherap y (MOPP/ABVD, n=5). The ADCC assay against extraocular muscle cells wa s increased in patients with Hodgkin's disease (5.5% vs. <1.0%, p=.026 ) when compared with controls. In addition, Hodgkin's disease patients treated with XRT (with or without chemotherapy) had significantly hig her ADCC tests than controls (9.7% vs. <1.0%, p=.010), In contrast, AD CC assays were not different between Hodgkin's disease patients treate d with chemotherapy alone and controls (<1.0% vs. <1.0%, p=.53). Hodgk in's patients treated with XRT had higher ADCC assays than those treat ed with chemotherapy alone (p=.087), although this difference did not achieve statistical significance. Serum measurements of antithyroid pe roxidase (TPO) antibodies, antithyroglobulin (Tg) antibodies, thyroid binding inhibitory immunoglobulins (TBII), and thyroid stimulating imm unoglobulin (TSI) were. similar in all groups. Antibodies against the 64 kDa orbital antigen were detected in 1 patient and 1 control subjec t. Excluding patients already treated with L-thyroxine for hypothyroid ism (n=5), free T-3, but not free T-4, was lower in the Hodgkin's dise ase group than in controls (2.2 pg/mL vs. 2.7 pg/mL, p=.008). Thyrotro pin (TSH) concentrations were not statistically different between thes e groups. In summary, these data show: (1) ADCC against human orbital muscle cells is increased in patients with Hodgkin's disease compared with controls: (2) these differences were noted among Hodgkin's diseas e patients treated with thyroidal XRT, with or without chemotherapy, a nd not among those patients treated with chemotherapy alone; and (3) n o statistically significant differences in the frequency of thyroid au toantibodies were found. These data suggest that patients with Hodgkin 's disease display altered antibody-dependent immune function toward e xtraocular muscle cells that may possibly be related to by ?CRT. Large r, prospective studies assessing thyroid and orbital-related immunolog ic abnormalities in Hodgkin's disease are warranted.