Background/Purpose: Autoantibodies (aAbs) to proteins comprising the survival of motor neuron (SMN) macromolecular complex have not been thoroughly studied. Only two publications described clinical associations related to anti-SMN: the seminal publication reported three patients for which anti-SMN was associated with myositis and myositis/SSc overlap, while the second reported a patient with necrotizing myopathy and aAbs to SMN1 and gemin3.  aAbs to the SMN complex may be suggested by indirect immunofluorescence (IIF) on HEp-2 cells showing a pattern referred to as few nuclear dots (known as AC-7 in the International Consensus on ANA patterns). The AC-7 pattern has been reported to have a low predictive value for any disease. Interestingly, deletion or mutation of SMN gene causes spinal muscular atrophy. The aim of this study was to describe the ANA pattern of patients with a SSc/myositis (scleromyositis) overlap syndrome (SMOS) with no known other SSc or myositis-specific aAbs; and to evaluate the clinical features of patients with a SMOS and anti-SMN aAbs.

Methods: Patients with a SMOS with no known SSc or myositis-specific aAbs were identified from 2 retrospective cohorts of patients with myositis and/or SSc. Both the diagnosis of myositis and SSc were made by expert opinion, since fulfilling the new classification criteria for both SSc and myositis may be insensitive in early disease. Sera from patients with the AC-7 pattern were tested for anti-SMN by an addressable laser bead immunoassay (ALBIA) and validated by immunoprecipitation (IP) of homogenates of metabolically labelled cells. ALBIA results were expressed as median fluorescence units (MFU) and the cut-off was set at 3 standard deviations above normal and unrelated disease controls.

Results: Twenty-one patients with SMOS and no known SSc or myositis-specific aAbs were identified, 6 of whom had an AC-7 IIF pattern. Anti-SMN aAbs were present on ALBIA in 5/6 (83.3%) of these patients (median 13 661 MFU; range 7433–21146). In these 5 patients positive on ALBIA, IP confirmed the reactivity to SMN and gemins 2, 3 or 4. Key myopathic features at presentation of these 5 patients were proximal weakness in all, with a mean CK elevation of 2564 IU/L (range 1738-3675). SSc features at the time of myositis diagnosis included Raynaud phenomenon (100%), limited (60%) or sine (40%) skin involvement, and bilateral trigeminal neuropathy (20%). At last follow-up, all patients met the ACR/EULAR classification criteria for SSc and notable SSc features included calcinosis (60%), pneumatosis intestinalis (20%), retro-pneumoperitoneum (20%) and interstitial lung disease (20%). Although all patients had been treated with corticosteroids, SSc renal crisis did not occur. Other overlap features included arthritis (60%), Sjögren syndrome (40%) and SLE (20%). One patient had 3 siblings with spinal muscular atrophy.

Conclusion: Single-specificity anti-SMN complex aAbs may define a novel SMOS, with absent or limited skin involvement at myositis diagnosis. The few nuclear dots (AC-7) pattern may be associated with clinically relevant information and be a sensitive screening test for anti-SMN aAbs in SMOS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-specificity-anti-smn-autoantibodies-are-associated-with-a-novel-scleromyositis-overlap-syndrome/