Background/Purpose: The survival of motor neuron (SMN)/gemin proteins are components of a multifunctional protein complex that plays an essential role in RNA metabolism. SMN is present in Cajal bodies, i.e. nuclear structures that play an essential role in the assembly of small nuclear RNPs. Deletion or mutation of the SMN gene is associated with spinal muscular atrophy. Autoantibodies (aAbs) to SMN (anti-SMN) have not been thoroughly studied. Anti-SMN have been associated with scleromyositis (SM), originally in a cohort of 163 autoimmune myositis (AIM) (n=3, 1.8%) patients, and recently in a cohort of 20 seronegative SM (n=5, 25%). In another report, a single patient with anti-U1RNP and anti-SMN aAbs had a necrotizing autoimmune myopathy. The aim of this study was to evaluate the prevalence of anti-SMN aAbs in patients with anti-U1RNP+ AIM, and compare phenotypic differences in patients with and without anti-SMN aAbs.

Methods: All patients with a diagnosis of AIM associated with anti-U1RNP were identified from a clinically and serologically described retrospective cohort of 100 AIM patients. Sera were analyzed for anti-SMN by addressable laser bead immunoassay with results expressed as median fluorescence units (MFU) and positivity defined as 3 SD above the mean of normal and unrelated disease controls ( >900 MFU), as previously validated by protein A-assisted immunoprecipitation. Clinical features were collected to assess the presence of ACR/EULAR and non ACR/EULAR features of systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and Sjögren syndrome (SS).

Results: Of 9 AIM patients with anti-U1RNP+, 8 (88.9%) were females and median age at myositis diagnosis was 45 years old (range 24–61). At presentation, clinical features included Raynaud phenomenon (100% of patients), sclerodactyly (100%), lower esophageal dysmotility (88%), arthritis (78%) and proximal weakness (100%). Mean serum CK level was 2601 IU/L (range 329–6000). At myositis diagnosis, 88%, 22% and 22% of 9 patients fulfilled the ACR/EULAR criteria for SSc, SLE and SS, respectively. Five of 9 patients (55.6%) had anti-SMN aAbs (median 15952 MFU, range 4321–18848). These patients had a higher proportion of neck flexor weakness (60% vs 0%), bilateral trigeminal neuropathy (40% vs 25%), interstitial lung disease (40% vs 0%), acute lupus rash (80% vs 25%) and leucopenia (80% vs 25%) compared to patients without anti-SMN aAbs. Strikingly, only patients with anti-SMN aAbs had SSc small-bowel involvement (n=4/5, 80% vs n=0/4, 0%, P=0.048 by Fisher’s exact test) that included pneumatosis intestinalis (n=2/4), small intestine bacterial overgrowth (n=3/4) and pseudo-obstruction (n=4/4). One of these patients required parenteral nutrition whereas 3 others presented severe pseudo-obstruction necessitating hospitalization. At last follow-up (mean duration 12 years), 100%, 22% and 67% of 9 patients fulfilled the ACR/EULAR criteria for SSc, SLE and SS, respectively.

Conclusion: More than 50% of patients with anti-U1RNP+ AIM and SSc also have high titers of anti-SMN aAbs. The presence of anti-SMN aAbs may be predictive of severe SSc small bowel involvement compared to patients without anti-SMN aAbs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-smn-autoantibodies-are-associated-with-systemic-sclerosis-small-bowel-involvement-in-anti-u1rnp-positive-autoimmune-myositis/