Antibody Responses to Two Epstein-Barr Virus Nuclear Antigens Defined by Gene Transfer

By transfecting small fragments of Epstein-Barr virus (EBV) DNA into cells, we defined two nuclear antigens, termed M and K, and examined serum from 258 subjects for antibodies against these antigens. We hoped to learn whether such single-antigen systems would clarify the association of EBV with various diseases. Although reactivity to M antigen was found in only 14 per cent of healthy EBV-seropositive subjects, 90 per cent of Chinese and North African patients with nasopharyngeal carcinoma had antibody to M. Nearly all persons (96 per cent) who were EBV seropositive, as judged by their serologic reaction to a nuclear antigen encoded by the complete virus (EBNA), had a reaction to K antigen. However, serum samples from three patients with chronic active EBV infection did not react to K, even though the serum contained anti-M titers above 1:1000. Lymphoid cells from one such patient carried a normal gene for K and made K protein of correct size. Therefore, in this patient the absence of antibody to K had not resulted from a viral mutation that destroyed the K protein. These serologic studies show that some patients with chronic active EBV infection have an abnormal immune response to a specific viral gene product. (N Engl J Med 1985; 312:750–5.) ANTIBODY responses to the Epstein–Barr virus (EBV) are an important element of the association of the virus with infectious mononucleosis, endemic Burkitt's lymphoma, and nasopharyngeal carcinoma. 1 2 3 4 For example, screening for nasopharyngeal carcinoma in China depends on the presence of serum IgA antibodies to viral antigens. 5 , 6 Some patients with chronic active EBV infection have exceedingly high antibody titers to viral components. 7 By contrast, patients with immunodeficiency, who have diffuse lymphoproliferative syndromes due to EBV, often have impaired serologic responses, particularly to the Epstein–Barr nuclear antigen (EBNA). 8 When such serologic and diagnostic studies have been performed previously, they have employed complex antigens . . .