Autoantibodies to survival of motor neuron complex in patients with polymyositis: Immunoprecipitation of D, E, F, and G proteins without other components of small nuclear ribonucleoproteins

Minoru Satoh, Jason Y F Chan, Steven J. Ross, Angela Ceribelli, Ilaria Cavazzana, Franco Franceschini, Yi Li, Westley H. Reeves, Eric S. Sobel, Edward K L Chan

Research output: Contribution to journalArticle

Abstract

Objective Autoantibodies in the systemic rheumatic diseases are clinically useful biomarkers of the diagnosis or of certain clinical characteristics. An unusual pattern of immunoprecipitation, in which the D, E, F, and G proteins of small nuclear RNPs (snRNP) but without other components of the snRNP, was noticed at the autoantibody screening. The purpose of this study was to examine the target antigens and clinical manifestations associated with this specificity. Methods Autoantibodies in sera from 1,966 American patients (including 434 with systemic lupus erythematosus, 121 with scleroderma, 86 with polymyositis/dermatomyositis [PM/DM]) and 248 Italian patients with autoimmune diseases were screened by immunoprecipitation of 35S-methionine- labeled cell extracts. Sera with which D, E, F, and G proteins of snRNP was immunoprecipitated, but without the other snRNP proteins, were further examined by analysis of RNA components by immunoprecipitation (silver staining), Western blotting using survival of motor neuron (SMN) complex, and immunofluorescence. Results Three sera that immunoprecipitated D, E, F, and G proteins without other components (U1-70K, A, B-/B, C) of the snRNP were found. Four additional proteins (130 kd, 120 kd, 38 kd, and 33 kd) were also commonly immunoprecipitated. The target antigen was identified as SMN complex (Gemin 3, Gemin 4, SMN, and Gemin 2, respectively), which plays a critical role in the assembly of snRNP. In immunofluorescence analyses, all 3 sera showed nuclear dots (Cajal bodies) and cytoplasmic staining. Only 1 serum was weakly positive on Western blotting of SMN, suggesting that these sera mainly recognize native molecule or quaternary structure. All 3 patients were white women with PM, an interesting finding, since deletion or mutation of SMN is known to cause spinal muscular atrophy. Conclusion SMN complex was identified as a new Cajal body autoantigen recognized by sera from white patients with PM. The biologic and clinical significance of anti-SMN autoantibodies will need to be clarified.

Original languageEnglish
Pages (from-to)1972-1978
Number of pages7
JournalArthritis and Rheumatism
Volume63
Issue number7
DOIs
Publication statusPublished - Jul 2011

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

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