Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity

Iago Pinal-Fernandez, David R. Amici, Cassie A. Parks, Assia Derfoul, Maria Casal-Dominguez, Katherine Pak, Richard Yeker, Paul Plotz, Jose C. Milisenda, Josep M. Grau-Junyent, Albert Selva-O'Callaghan, Julie Paik, Jemima Albayda, Andrea Markl Corse, Thomas Lloyd, Lisa Christopher-Stine, Andrew L. Mammen

Research output: Contribution to journalArticle

Abstract

Objective: Although more than a dozen myositis-specific autoantibodies (MSAs) have been identified, most patients with myositis are positive for a single MSA. The specific overexpression of a given myositis autoantigen in myositis muscle has been proposed as initiating and/or propagating autoimmunity against that particular autoantigen. The present study was undertaken to test this hypothesis. Methods: In order to quantify autoantigen RNA expression, RNA sequencing was performed on muscle biopsy samples from control subjects, MSA-positive patients with myositis, regenerating mouse muscles, and cultured human muscle cells. Results: Muscle biopsy samples were available from 20 control subjects and 106 patients with autoantibodies recognizing hydroxymethylglutaryl-coenzyme A reductase (n = 40), signal recognition particles (n = 9), Jo-1 (n = 18), nuclear matrix protein 2 (n = 12), Mi-2 (n = 11), transcription intermediary factor 1γ (n = 11), or melanoma differentiation–associated protein 5 (n = 5). The increased expression of a given autoantigen in myositis muscle was not associated with autoantibodies recognizing that autoantigen (all q > 0.05). In biopsy specimens from both myositis muscle and regenerating mouse muscles, autoantigen expression correlated directly with the expression of muscle regeneration markers and correlated inversely with the expression of genes encoding mature muscle proteins. Myositis autoantigens were also expressed at high levels in cultured human muscle cells. Conclusion: Most myositis autoantigens are highly expressed during muscle regeneration, which may relate to the propagation of autoimmunity. However, factors other than overexpression of specific autoantigens are likely to govern the development of unique autoantibodies in individual patients with myositis.

Original languageEnglish (US)
JournalArthritis and Rheumatology
DOIs
StatePublished - Jan 1 2019

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Myositis
Autoantigens
Autoantibodies
Regeneration
Muscles
Autoimmunity
Biopsy
Muscle Cells
Signal Recognition Particle
RNA Sequence Analysis
Muscle Proteins
Coenzyme A
Melanoma
Oxidoreductases
Transcription Factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Pinal-Fernandez, I., Amici, D. R., Parks, C. A., Derfoul, A., Casal-Dominguez, M., Pak, K., ... Mammen, A. L. (2019). Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity. Arthritis and Rheumatology. https://doi.org/10.1002/art.40883

Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity. / Pinal-Fernandez, Iago; Amici, David R.; Parks, Cassie A.; Derfoul, Assia; Casal-Dominguez, Maria; Pak, Katherine; Yeker, Richard; Plotz, Paul; Milisenda, Jose C.; Grau-Junyent, Josep M.; Selva-O'Callaghan, Albert; Paik, Julie; Albayda, Jemima; Corse, Andrea Markl; Lloyd, Thomas; Christopher-Stine, Lisa; Mammen, Andrew L.

In: Arthritis and Rheumatology, 01.01.2019.

Research output: Contribution to journalArticle

Pinal-Fernandez, I, Amici, DR, Parks, CA, Derfoul, A, Casal-Dominguez, M, Pak, K, Yeker, R, Plotz, P, Milisenda, JC, Grau-Junyent, JM, Selva-O'Callaghan, A, Paik, J, Albayda, J, Corse, AM, Lloyd, T, Christopher-Stine, L & Mammen, AL 2019, 'Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity', Arthritis and Rheumatology. https://doi.org/10.1002/art.40883
Pinal-Fernandez, Iago ; Amici, David R. ; Parks, Cassie A. ; Derfoul, Assia ; Casal-Dominguez, Maria ; Pak, Katherine ; Yeker, Richard ; Plotz, Paul ; Milisenda, Jose C. ; Grau-Junyent, Josep M. ; Selva-O'Callaghan, Albert ; Paik, Julie ; Albayda, Jemima ; Corse, Andrea Markl ; Lloyd, Thomas ; Christopher-Stine, Lisa ; Mammen, Andrew L. / Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity. In: Arthritis and Rheumatology. 2019.
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abstract = "Objective: Although more than a dozen myositis-specific autoantibodies (MSAs) have been identified, most patients with myositis are positive for a single MSA. The specific overexpression of a given myositis autoantigen in myositis muscle has been proposed as initiating and/or propagating autoimmunity against that particular autoantigen. The present study was undertaken to test this hypothesis. Methods: In order to quantify autoantigen RNA expression, RNA sequencing was performed on muscle biopsy samples from control subjects, MSA-positive patients with myositis, regenerating mouse muscles, and cultured human muscle cells. Results: Muscle biopsy samples were available from 20 control subjects and 106 patients with autoantibodies recognizing hydroxymethylglutaryl-coenzyme A reductase (n = 40), signal recognition particles (n = 9), Jo-1 (n = 18), nuclear matrix protein 2 (n = 12), Mi-2 (n = 11), transcription intermediary factor 1γ (n = 11), or melanoma differentiation–associated protein 5 (n = 5). The increased expression of a given autoantigen in myositis muscle was not associated with autoantibodies recognizing that autoantigen (all q > 0.05). In biopsy specimens from both myositis muscle and regenerating mouse muscles, autoantigen expression correlated directly with the expression of muscle regeneration markers and correlated inversely with the expression of genes encoding mature muscle proteins. Myositis autoantigens were also expressed at high levels in cultured human muscle cells. Conclusion: Most myositis autoantigens are highly expressed during muscle regeneration, which may relate to the propagation of autoimmunity. However, factors other than overexpression of specific autoantigens are likely to govern the development of unique autoantibodies in individual patients with myositis.",
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AU - Pinal-Fernandez, Iago

AU - Amici, David R.

AU - Parks, Cassie A.

AU - Derfoul, Assia

AU - Casal-Dominguez, Maria

AU - Pak, Katherine

AU - Yeker, Richard

AU - Plotz, Paul

AU - Milisenda, Jose C.

AU - Grau-Junyent, Josep M.

AU - Selva-O'Callaghan, Albert

AU - Paik, Julie

AU - Albayda, Jemima

AU - Corse, Andrea Markl

AU - Lloyd, Thomas

AU - Christopher-Stine, Lisa

AU - Mammen, Andrew L.

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N2 - Objective: Although more than a dozen myositis-specific autoantibodies (MSAs) have been identified, most patients with myositis are positive for a single MSA. The specific overexpression of a given myositis autoantigen in myositis muscle has been proposed as initiating and/or propagating autoimmunity against that particular autoantigen. The present study was undertaken to test this hypothesis. Methods: In order to quantify autoantigen RNA expression, RNA sequencing was performed on muscle biopsy samples from control subjects, MSA-positive patients with myositis, regenerating mouse muscles, and cultured human muscle cells. Results: Muscle biopsy samples were available from 20 control subjects and 106 patients with autoantibodies recognizing hydroxymethylglutaryl-coenzyme A reductase (n = 40), signal recognition particles (n = 9), Jo-1 (n = 18), nuclear matrix protein 2 (n = 12), Mi-2 (n = 11), transcription intermediary factor 1γ (n = 11), or melanoma differentiation–associated protein 5 (n = 5). The increased expression of a given autoantigen in myositis muscle was not associated with autoantibodies recognizing that autoantigen (all q > 0.05). In biopsy specimens from both myositis muscle and regenerating mouse muscles, autoantigen expression correlated directly with the expression of muscle regeneration markers and correlated inversely with the expression of genes encoding mature muscle proteins. Myositis autoantigens were also expressed at high levels in cultured human muscle cells. Conclusion: Most myositis autoantigens are highly expressed during muscle regeneration, which may relate to the propagation of autoimmunity. However, factors other than overexpression of specific autoantigens are likely to govern the development of unique autoantibodies in individual patients with myositis.

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