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 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.
Badenhoop
K
K
Center of Internal Medicine, University Hospital, Frankfurt am Main, Germany. badenhoop@em.uni-frankfurt.de
Donner
H
H
Neumann
J
J
Herwig
J
J
Kurth
R
R
Usadel
K H
KH
Tönjes
R R
RR
D000917:Antibody Formation / Q000502:physiology; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012016:Reference Values; D012190:Retroviridae / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
D012333:RNA, Messenger; D012367:RNA, Viral; D014759:Viral Envelope Proteins