ABSTRACT
INTRODUCTION: Paraneoplastic autoantibody screening of 150,000 patient sera by tissue-based immunofluorescence incidentally revealed 170 with unsuspected signal recognition particle (SRP) immunoglobulin G (IgG), which is a recognized biomarker of autoimmune myopathy. Of the 77 patients with available information, 54 had myopathy. We describe the clinical/laboratory associations. METHODS: Distinctive cytoplasm-binding IgG (mouse tissue substrate) prompted western blot, enzyme-linked immunoassay, and immunoprecipitation analyses. Available histories were reviewed. RESULTS: The immunostaining pattern resembled rough endoplasmic reticulum, and mimicked Purkinje-cell cytoplasmic antibody type 1 IgG/anti-Yo. Immunoblotting revealed ribonucleoprotein reactivity. Recombinant antigens confirmed the following: SRP54 IgG specificity alone (17); SRP72 IgG specificity alone (3); both (32); or neither (2). Coexisting neural autoantibodies were identified in 28% (low titer). Electromyography revealed myopathy with fibrillation potentials; 78% of biopsies had active necrotizing myopathy with minimal inflammation, and 17% had inflammatory myopathy. Immunotherapy responsiveness was typically slow and incomplete, and relapses were frequent on withdrawal. Histologically confirmed cancers (17%) were primarily breast and hematologic, with some others. CONCLUSIONS: Autoimmune necrotizing SRP myopathy, both idiopathic and paraneoplastic, is underdiagnosed in neurological practice. Serological screening aids early diagnosis. Cancer surveillance and appropriate immunosuppressant therapy may improve outcome. Muscle Nerve 53: 925-932, 2016.
Subject(s)
Autoimmune Diseases , Immunoglobulin G/blood , Muscular Diseases , Signal Recognition Particle/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/immunology , Autoimmune Diseases/blood , Autoimmune Diseases/complications , Autoimmune Diseases/immunology , Brain/metabolism , Brain/pathology , Electromyography , Enzyme-Linked Immunosorbent Assay , Female , Glutamate Decarboxylase , Humans , Immunoglobulin G/metabolism , Immunoprecipitation , Male , Middle Aged , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscular Diseases/blood , Muscular Diseases/complications , Muscular Diseases/immunology , Neurons/metabolism , RNA, Messenger/metabolism , Signal Recognition Particle/classification , Signal Recognition Particle/genetics , Young AdultABSTRACT
The signal recognition particle (SRP) is a phylogenetically conserved ribonucleoprotein that associates with ribosomes to mediate the targeting of membrane and secretory proteins to biological membranes. In higher eukaryotes, SRP biogenesis involves the sequential binding of SRP19 and SRP54 proteins to the S domain of 7S RNA. The recently determined crystal structures of SRP19 in complex with the S domain, and that of the ternary complex of SRP19, the S domain and the M domain of SRP54, provide insight into the molecular basis of S-domain assembly and SRP function.
