0154: Anti-SMN Autoantibodies in Mixed Connective Tissue Disease Are Associated with a Scleromyositis Phenotype

Hajar El Kamouni¹, Alexandra Albert², Sabrina Hoa³, Darya S. Jalaledin⁴, Josiane Bourre-Tessier⁵, Eric Rich⁵, Jean-Richard Goulet⁶, Martial Koenig⁷, Minoru Satoh⁸, Marvin Fritzler⁹, May Choi¹⁰, Yves Troyanov¹¹, Jean-Luc Senécal⁵ and Océane Landon-Cardinal⁵, ¹Division of Rheumatology, Centre Hospitalier de l'Université de Montréal, Laval, Canada, ²Division of Rheumatology, Centre Hospitalier de l'Université Laval, Québec, QC, Canada, ³University of Montreal, Montréal, QC, Canada, ⁴Division of Internal Medicine, Centre Hospitalier de l'Université de Sherbrooke, Saint-Lambert, Canada, ⁵Division of Rheumatology, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada, ⁶Division of Rheumatology, Centre Hospitalier de l'Université de Montréal, Saint-Lambert, Canada, ⁷Division of Internal Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada, ⁸Department of Human, Information and Science, University of Occupational Environmental Health, Kitakyusyu Fukuoka, Japan, ⁹University of Calgary, Calgary, AB, Canada, ¹⁰Brigham and Women's Hospital | University of Calgary, Calgary, AB, Canada, ¹¹Division of Rheumatology, Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada

Background/Purpose: The survival of motor neuron (SMN) is a ubiquitous macromolecular complex, located in the Cajal body of mammalian nuclei, with an essential role in assembly of small nuclear RNPs. Recent data have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in scleromyositis, and as a potential biomarker for severe small bowel involvement in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of Mixed Connective Tissue Disease (MCTD) patients with and without anti-SMN aAbs.

Methods: Anti-U1RNP+ MCTD patients from a previously clinically and serologically described retrospective cohort were studied. Patients fulfilling ≥ 1 MCTD classification of Alarcon-Segovia (AS), Kasukawa (Ka), Kahn (Kn) and/or Tanaka (Ta) were included. An addressable laser bead immunoassay utilizing a full-length recombinant human protein was used to detect specific anti-SMN aAbs with normal reference range of < 300 mean fluorescence intensity (MFI) to classify 300-999 MFI as low-titer and ≥ 1000 MFI as high-titer positivity.

Clinical features were assessed for the presence of ACR/EULAR and non ACR/EULAR features of systemic sclerosis (SSc), systemic lupus erythematosus (SLE), Sjögren syndrome (SS) and myositis. Comparisons among anti-SMN+ and anti-SMN- subgroups used Fisher two-tailed exact test. Logistic regression analyses (univariable and multivariable adjusted for sex, age at diagnosis and disease duration) with 95% confidence intervals performed on outcomes of interest.

Results: Sixty-six patients were included and MCTD criteria were respectively fulfilled in 86% (AS), 73% (Ka), 97% (Kn) and 98% (Ta) patients. Fifty-eight patients (88%) were females and median age at MCTD diagnosis was 41 years (range 11–70 years). At last follow-up (median duration 12 years), 71%, 81% and 12% of 66 patients fulfilled the ACR/EULAR criteria for SSc, SLE and SS, respectively. Thirty-nine of 66 (59%) patients were positive for anti-SMN aAbs: 10 (26%) had low-titer and 29 (74%) had high-titer anti-SMN, based on highest available titer during follow-up.The presence of anti-SMN aAbs in MCTD patients was associated with a higher risk of fingertip pitting scars (23% anti-SMN+ vs 4% anti-SMN-, p=0.04), lower gastrointestinal (GI) involvement (defined as pneumatosis and/or pseudoobstruction and/or small intestinal bacterial overgrowth)

(26% vs 4%, p=0.039), myositis (37% vs 15%, p=0.09), and myocarditis (16% vs 0%, p=0.037).

On multivariable logistic regression, the risk of myositis or lower GI involvement was highest among patients with high-titer anti-SMN: adjusted OR 4.30 (95% CI, 1.11-19.86, p=0.04) and 11.99 (95% CI, 1.82-248.08, p=0.03), respectively.

The combined outcome of pitting scars and/or lower GI involvement and/or myositis and/or myocarditis was highest among those with high-titer anti-SMN: adjusted OR 7.79 (2.33-30.45, p=0.002).

Conclusion: Anti-SMN aAbs were present in 59% of patients in this criteria-defined MCTD cohort. The presence of anti-SMN aAbs, especially with high titers, were associated with a higher prevalence of myositis and SSc features, i.e., scleromyositis, compared to patients without anti-SMN aAbs.

Disclosures: H. El Kamouni, None; A. Albert, None; S. Hoa, None; D. S. Jalaledin, None; J. Bourre-Tessier, None; E. Rich, None; J. Goulet, None; M. Koenig, None; M. Satoh, None; M. Fritzler, Mitogen Diagnostics Corporation; M. Choi, AstraZeneca, MitogenDx, mallinckrodt, Janssen, AbbVie/Abbott, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol-Myers Squibb(BMS), Celltrion, Ferring, Fresenius Kabi, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche; Y. Troyanov, None; J. Senécal, None; O. Landon-Cardinal, None.