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

Abstract

Recently, human endogenous retrovirus type K (HERV-K [IDDMK(1,2)22]) was isolated from an IDDM patient's beta-cell supernatant and shown to be implicated 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 terminal repeat element of the HLA DQ gene (DQ-LTR) to be positively associated with IDDM, which led us to investigate whether DQ-LTR is related to transcription of the putative retroviral superantigen. Additionally, we sought immunological evidence to determine whether those retroviral antigens could evoke an antibody response. Patients with IDDM (n = 14), Hashimoto's thyroiditits (n = 5), and Graves' disease (n = 12), as well as healthy control subjects (n = 12), were investigated, as were four nuclear families of Graves' disease patients and two of IDDM patients. RNA was isolated from plasma and peripheral blood lymphocytes and subjected to reverse transcription-polymerase chain reaction for transcripts of the env region of the HERV-K (IDDMK(1,2)22) sequence. We identified env transcripts in both plasma and peripheral blood lymphocytes in all individuals studied: patients with recent-onset or long-standing IDDM, their relatives, and healthy control subjects, as well as patients with thyroid autoimmune disorders. Furthermore, we screened the sera of patients (n = 62) and control subjects (n = 35) for evidence of humoral immunity against HERV-K by Western blot specific for the ENV protein. Similar frequencies of antibody-positives were observed both in patients with IDDM (29%) and in healthy control subjects (26%). We conclude that neither the ubiquitous HERV-K transcripts nor the comparable percentage of ENV protein antibodies are associated with IDDM. An earlier, presymptomatic antibody response against HERV-K (IDDMK(1,22)22) ENV cannot be ruled out. However, the superantigen hypothesis of an endogenous retrovirus in beta-cell autoimmunity awaits confirmation.