Signal recognition particle immunoglobulin g detected incidentally associates with autoimmune myopathy

Metha Apiwattanakul, Margherita Milone, Sean J Pittock, Thomas J. Kryzer, James P. Fryer, Orna O'toole, Andrew B McKeon, Vanda A Lennon

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
JournalMuscle and Nerve
DOIs
StateAccepted/In press - 2016

Fingerprint

Signal Recognition Particle
Muscular Diseases
Immunoglobulins
Immunoglobulin G
Autoantibodies
Myositis
Ribonucleoproteins
Rough Endoplasmic Reticulum
Purkinje Cells
Electromyography
Immunosuppressive Agents
Immunoenzyme Techniques
Immunoprecipitation
Immunoblotting
Immunotherapy
Fluorescent Antibody Technique
Early Diagnosis
Neoplasms
Cytoplasm
Breast

Keywords

  • Autoantibody
  • Necrotizing myopathy
  • Paraneoplastic
  • Serological marker

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)
  • Physiology

Cite this

Signal recognition particle immunoglobulin g detected incidentally associates with autoimmune myopathy. / Apiwattanakul, Metha; Milone, Margherita; Pittock, Sean J; Kryzer, Thomas J.; Fryer, James P.; O'toole, Orna; McKeon, Andrew B; Lennon, Vanda A.

In: Muscle and Nerve, 2016.

Research output: Contribution to journalArticle

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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.",
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AU - Fryer, James P.

AU - O'toole, Orna

AU - McKeon, Andrew B

AU - Lennon, Vanda A

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N2 - 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.

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