Involvement of human intracisternal A‐type retroviral particles in autoimmunity

Abstract

Prior studies have linked retroviruses to various arthropathies and autoimmune diseases. Sjögren's syndrome (SS), a systemic autoimmune disease, is characterized by aggressive infiltration of lymphocytes into the salivary and lacrimal glands, resulting in destruction of the glands and dry mouth and eyes (sicca syndrome). The infiltrating lymphocytes in SS may become overtly malignant, and thus, the incidence of lymphoma is greatly increased in SS patients. A human intracisternal A-type retroviral particle type I (HIAP-I) has been isolated from persons with SS. HIAP-I shares a limited number of antigenic epitopes with human immunodeficiency virus (HIV), but is distinguishable from HIV by morphological, physical, and biochemical criteria. A substantial majority of patients with SS or systemic lupus erythematosus (SLE) have serum antibodies to the proteins of this human retrovirus. Fewer than 3% of the normal blood donor population have antibodies to any HIAP-associated proteins. A second type of a human intracisternal A-type retrovirus, HIAP-II, was detected in a subset of patients with idiopathic CD4 lymphocytopenia (ICL), an AIDS-like immunodeficiency disease. Most HIAP-II positive ICL patients were also antinuclear antibody positive. Reviewed here are additional studies from several laboratories suggesting that HIAP or related viruses may be involved in SLE and other autoimmune conditions. Additionally, results of comprehensive surveys of autoimmune patients to determine seroreactivity to HIAP, and other human retroviruses, including HIV and human T-lymphotropic virus type I, are reported.

Persistent Viral Infection in Primary Sjogren’s Syndrome: Review and Perspectives

“…Similar results were found by Yamano et al who also observed IAPs in epithelial cells of pSS patients with electron microscopy [20]. Later on, Sander et al showed that patients with pSS, systemic lupus erythematosus, Still's disease, and idiopathic T lymphocytopenia have antibodies against purified IAP proteins [21]. These results lead to several questions that deserve further investigation:…”

An IAP retrotransposon in the mouse ADAMTS13 gene creates ADAMTS13 variant proteins that are less effective in cleaving von Willebrand factor multimers

“…[18][19][20] IAP may also be involved in the pathogenesis of certain autoimmune diseases. 21 An IAP element of 6026 base pairs is located in intron 23 of the ADAMTS13 gene in some strains of mice. 22 This IAP element is 92% homologous to the MIA14 IAP element (M17551) originally identified in the kappa light-chain gene of a mouse hybridoma cell line.…”

Endogenous retroelements and autoimmune disease

“…Because of their abrupt appearance in a tissue, these proteins could bypass or override tolerance mechanisms that delete lymphocytes specific for constitutive self antigens. This antigen-based mechanism has been proposed in the context of multiple sclerosis [8], SLE [9], Sjogrens syndrome [10], and other autoimmune disorders in which specific retroviruses may give rise to the targeted autoantigens. Although the proteins of retroelements could in principle serve as antigens, there is no clear evidence for an autoimmune disease caused by autoreactive lymphocyte responses to endogenous retroviral antigens.…”