Recognising the spectrum of scleromyositis: HEp-2 ANA patterns allow identification of a novel clinical subset with anti-SMN autoantibodies.

Abstract

OBJECTIVE:

To describe systemic sclerosis (SSc) with myopathy in patients without classic SSc-specific and SSc-overlap autoantibodies (aAbs), referred to as seronegative scleromyositis.

METHODS:

Twenty patients with seronegative scleromyositis diagnosed by expert opinion were analysed retrospectively for SSc features at myositis diagnosis and follow-up, and stratified based on HEp-2 nuclear patterns by indirect immunofluorescence (IIF) according to International Consensus of Autoantibody Patterns. Specificities were analysed by protein A-assisted immunoprecipitation. Myopathy was considered an organ involvement of SSc.

RESULTS:

SSc sine scleroderma was a frequent presentation (45%) at myositis diagnosis. Myositis was the most common first non-Raynaud manifestation of SSc (55%). Lower oesophagal dysmotility was present in 10 of 11 (91%) investigated patients. At follow-up, 80% of the patients met the American College of Rheumatology/EULAR SSc classification criteria. Two-thirds of patients had a positive HEp-2 IIF nuclear pattern (all with titers ≥1/320), defining three novel scleromyositis subsets. First, antinuclear antibody (ANA)-negative scleromyositis was associated with interstitial lung disease (ILD) and renal crisis. Second, a speckled pattern uncovered multiple rare SSc-specific aAbs. Third, the nuclear dots pattern was associated with aAbs to survival of motor neuron (SMN) complex and a novel scleromyositis subset characteriszed by calcinosis but infrequent ILD and renal crisis.

CONCLUSIONS:

SSc skin involvement is often absent in early seronegative scleromyositis. ANA positivity, Raynaud phenomenon, SSc-type capillaroscopy and/or lower oesophagal dysmotility may be clues for scleromyositis. Using HEp-2 IIF patterns, three novel clinicoserological subsets of scleromyositis emerged, notably (1) ANA-negative, (2) ANA-positive with a speckled pattern and (3) ANA-positive with nuclear dots and anti-SMN aAbs.

• Authors: Océane Landon-Cardinal, Alexandra Baril-Dionne, Sabrina Hoa, Alain Meyer, Valérie Leclair, Josiane Bourré-Tessier, Anne-Marie Mansour, Farah Zarka, Jean-Paul Makhzoum, Jessica Nehme, Eric Rich, Jean-Richard Goulet, Tamara Grodzicky, Martial Koenig, France Joyal, Isabelle Richard, Marie Hudson, Ira Targoff, Minoru Satoh, Marvin J Fritzler, Yves Troyanov, Jean-Luc Senécal
• Journal: RMD open (RMD Open) Vol. 6 Issue 2 (09 2020) ISSN: 2056-5933 [Electronic] England
• PMID: 32892170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antibodies, Antinuclear
• Autoantibodies
• SMN Complex Proteins

Topics

• Antibodies, Antinuclear (blood, immunology)
• Autoantibodies (blood, immunology)
• Autoimmunity
• Disease Susceptibility
• Female
• Fluorescent Antibody Technique, Indirect
• Humans
• Immunoprecipitation
• Male
• Myositis (blood, diagnosis, etiology)
• Retrospective Studies
• SMN Complex Proteins (immunology)
• Scleroderma, Systemic (blood, diagnosis, etiology)
• Serologic Tests