PubMed · 7541112
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L Steinman. 1995-06-29. Multiple sclerosis. Presenting an odd autoantigen.. https://doi.org/10.1038/375739b0
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We previously identified a complex of 3' --> 5' exoribonucleases, designated the exosome, that is expected to play a major role in diverse RNA processing and degradation pathways. Further biochemical and genetic analyses have revealed six novel components of the complex. Therefore, the complex contains 11 components, 10 of which are predicted to be 3' --> 5' exoribonucleases on the basis of sequence homology. Human homologs were identified for 9 of the 11 yeast exosome components, three of which complement mutations in the respective yeast genes. Two of the newly identified exosome components are homologous to known components of the PM-Scl particle, a multisubunit complex recognized by autoimmune sera of patients suffering from polymyositis-scleroderma overlap syndrome. We demonstrate that the homolog of the Rrp4p exosome subunit is also a component of the PM-Scl complex, thereby providing compelling evidence that the yeast exosome and human PM-Scl complexes are functionally equivalent. The two complexes are similar in size, and biochemical fractionation and indirect immunofluorescence experiments show that, in both yeast and humans, nuclear and cytoplasmic forms of the complex exist that differ only by the presence of the Rrp6p/PM-Scl100 subunit exclusively in the nuclear complex.
Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4(+) T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.
A RARE DISEASE: Paraneoplastic pemphigus is an rare autoimmune bullous skin disease recently recognized. About 50 cases have been reported since its first description in 1990. CLINICAL MANIFESTATIONS: Clinical signs are polymorphous resembling the cutaneomucosal manifestations of pemphigus vulgar (skin and mucosa erosions, fragile interdermal bullae), pemphigoid (urticaria, distended subepidermal bullae), and polymorphous erythema (plaque lesions). Mucosal erosions predominate however. ASSOCIATED CANCERS: Most cancers associated with paraneoplastic pemphigus are hematologic diseases (non-Hodgkin's lymphomas, chronic lymphoid leukemia). SEVERE PROGNOSIS: No standard treatment has been defined. General corticosteroids and treatment of the causal disease are indicated. The clinical course of paraneoplastic pemphigus does not always follow the course of the associated neoplasm. POSITIVE DIAGNOSIS: Pathology criteria (keratinocyte necrosis, suprabasal keratinocyte vacuolization, intraepidermal acantholysis) and immunohistological findings (antibody and complement deposits at the dermo-epidermal junction and within the keratinocytes on different epithelial substrates) are insufficient for positive diagnosis. Autoantibodies must be identified by immunoprecipitation or immunoblotting to identify the target antigen complex plakin components (desmoplakin I and II, periplakin, envoplakin), the major pemphigoid antigen, desmoglein 3, and certain yet unidentified antigens with a molecular weight of 170 kD. PATHOGENESIS: Paraneoplastic pemphigus appears as a model autoimmune paraneoplastic disease. Its origin remains elusive. It has been hypothesized that tumor-induced inhibition of tolerance to certain antigens implicated in the keratinocyte junctional systems could be involved.