Evidence for a novel picornavirus in human dermatomyositis

Abstract

We prepared RNA probes from cloned segments of human and murine enteroviruses (EVs) for in situ hybridization of skeletal muscle biopsies from patients with dermatomyositis (DM), polymyositis, other inflammatory myopathies, and noninflammatory muscle diseases, and from normal control subjects. A probe derived from Theiler's murine encephalomyelitis virus (TMEV) detected viral RNA within mononuclear cells of the interstitial connective tissue in 3 of 5 patients with adult-onset DM. None of these patients showed positive hybridization to probes derived from human EVs (poliovirus type 1 and Coxsackie virus B3) applied to subjacent sections of the same biopsies. The remaining 2 adult DM patients, 4 patients with childhood-onset DM, and 24 non-DM patients did not react with either TMEV or human enterovirus probes. Histochemical stains for esterase and immunoperoxidase stains for Mac-1 antigen in the 3 DM patients who reacted positively revealed positive cells in the same distribution as, but in far greater number than, those positive by in situ hybridization. Immunoperoxidase staining for HLA-DR antigens revealed positive cells in the same distribution and number as were seen with the TMEV probe. We conclude that an EV-like agent, more closely related to TMEV than to human EVs, may be associated with DM and that this agent is probably localized within muscle macrophages that express class II major histocompatibility complex antigens.

New‐onset juvenile dermatomyositis. Comparisons with a healthy cohort and children with juvenile rheumatoid arthritis

“…Although Theiler's murine encephalomyelitis virus was identified in adult PM, none of the children with DM who have been studied were positive for this agent (31). One way to consider this information is to speculate that molecular mimicry is instrumental in disease perpetuation.…”

Dermatomyositis onset in the puerperium period

“…DM may be associated with malignant tumours3 or with viral infections,4 suggesting a possible role of both tumour immunity and/or viral infections in the pathogenesis of this disease. In contrast, little is known about the relationship between DM and pregnancy.…”

Nucleic acid detection systems for enteroviruses

“…rived EV probes (unpublished data). In a third in situ hybridization study of human tissues for EV infection, muscle biopsy specimens from 33 patients were blindly studied for EV RNA (77). When an RNA probe derived from TMEV was used, three of five specimens from patients with adult-onset dermatomyositis were positive; 15 patients with other types of inflammatory myopathy, 9 patients with noninflammatory myopathy, and 4 patients with no muscle disease were all negative by in situ hybridization.…”

“…In addition to being the causes of well-recognized acute diseases, EVs have been implicated in several chronic illnesses including juvenile onset diabetes mellitus (8,111), chronic fatigue syndrome (5), dermatomyositis and polymyositis (13,77), congenital hydrocephalus (38), and amyotropic lateral sclerosis (37). Evidence for these associations has been largely from serology or from nucleic acid hybridization studies (see below); definitive proof is lacking, and confirmatory studies remain to be done.…”