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- Title
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.
- Authors
Badenhoop, Klaus; Donner, Horst; Neumann, Jeannette; Herwig, Jurgen; Kurth, Reinhard; Usadel, Klaus Henning; Tonjes, Ralf R.; Badenhoop, K; Donner, H; Neumann, J; Herwig, J; Kurth, R; Usadel, K H; Tönjes, R R
- 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.
- Subjects
RETROVIRUSES; AMINO acid sequence; DIABETES; AUTOANTIBODIES; PROTEIN metabolism; RNA metabolism; COMPARATIVE studies; TYPE 1 diabetes; RESEARCH methodology; MEDICAL cooperation; POLYMERASE chain reaction; PROTEINS; REFERENCE values; RESEARCH; WESTERN immunoblotting; EVALUATION research; REVERSE transcriptase polymerase chain reaction; ANTIBODY formation
- Publication
Diabetes, 1999, Vol 48, Issue 1, p215
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.48.1.215