IDDM patients neither show humoral reactivities against endogenous retroviral envelope protein nor do they differ in retroviral mRNA expression from healthy relatives or normal individuals

Recently, human endogenous retrovirus type It (HERV-K [IDDMK(1,2)22]) was i solated from an IDDM patient's beta-cell supernatant and shown to be implic ated in expression as a superantigen. Furthermore, HERV-K RNA was found in plasma samples from newly diagnosed patients but not in those from healthy control subjects, We had earlier identified the presence of a HERV-K long t erminal repeat element of the HLA DQ gene (DQ-LTR) to be positively associa ted with IDDM, which led us to investigate whether DQ-LTR is related to tra nscription of the putative retroviral superantigen. Additionally, we sought immunological evidence to determine whether those retroviral antigens coul d evoke an antibody response. Patients with IDDM (n = 14), Hashimoto's thyr oiditits (n = 5), and Graves' disease (n = 12), as well as healthy control subjects (n = 12): were investigated, as were four nuclear families of Grav es' disease patients and two Of IDDM patients. RNA was isolated from plasma and peripheral blood lymphocytes and subjected to reverse transcription-po lymerase chain reaction for transcripts of the env region of the HERV-K (ID DMK(1,2)22) sequence, We identified ena transcripts in both plasma and peri pheral blood lymphocytes in all individuals studied: patients with recent-o nset or long-standing IDDM, their relatives, and healthy control subjects, as well as patients with thyroid autoimmune disorders. Furthermore, we scre ened the sera of patients (n = 62) and control subjects (n = 35) for eviden ce of humoral immunity against HERV-K by Western blot specific for the ENV protein. Similar frequencies of antibody-positives were observed both in pa tients with IDDM (29%) and in healthy control subjects (26%), We conclude t hat neither the ubiquitous HERV-K transcripts nor the comparable percentage of ENV protein antibodies are associated with IDDM. An earlier, presymptom atic antibody response against HERV-K (IDDMK(1,22)22) ENV cannot be ruled o ut. However the superantigen hypothesis of an endogenous retrovirus in beta -cell autoimmunity awaits confirmation.