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

Abstract

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

Understanding the value of non-specific abnormal capillary dilations in presence of Raynaud’s phenomenon: a detailed capillaroscopic analysis

“…That is rather not surprising since it mirrors the previously reported association between the RMD Open RMD Open RMD Open presence of microvascular damage and anti-Scl70 Abs (immune system activation) with an higher risk of disease progression. [44][45][46][47] Collectively taken, these findings support the essential role of NVC for properly approaching and managing RP patients, together with a complete clinical evaluation and laboratory assessment. 48 Particularly, capillaroscopic non-specific abnormalities preceding the 'scleroderma pattern' seem to be a 'very early' preclinical hallmark to be accurately detected and monitored since they may represent potential precursor signals of an incoming overt and progressive SSc-related microangiopathy.…”

Anti-RuvBL1/2 autoantibodies in patients with systemic sclerosis or idiopathic inflammatory myopathy and a nuclear speckled pattern

“…Anti-RuvBL1/2 autoantibodies have recently been described in patients with systemic sclerosis (SSc) and SSc-myositis overlap syndrome, primarily in patients without other known autoantibodies. [2][3][4][5][6] Thirteen of 15 anti-RuvBL1/2-positive patients (87%) with description of HEp-2 IIF results in literature had a nuclear speckled pattern. In this study, we evaluated the presence of anti-RuvBL1/2 autoantibodies in patients with SSc or idiopathic inflammatory myopathy (IIM) with a nuclear speckled pattern on HEp-2 IIF without other known associated autoantibodies from two tertiary referral centres in Belgium, the University Hospitals Leuven and Ghent University Hospital.…”

“…Anti-RuvBL1/2 autoantibodies have recently been described in patients with systemic sclerosis (SSc) and SSc-myositis overlap syndrome, primarily in patients without other known autoantibodies 2–6. Thirteen of 15 anti-RuvBL1/2-positive patients (87%) with description of HEp-2 IIF results in literature had a nuclear speckled pattern.…”

The Involvement of Smooth Muscle, Striated Muscle, and the Myocardium in Scleroderma: A Review

“…The authors hypothesized that myositis might represent an early SSc manifestation since it was present in 55% of the subjects as the first non-Raynaud manifestation. Moreover, skin involvement was absent in almost half of the patients at the time of myositis diagnosis, while several features (Raynaud’s phenomenon, ANA, SSc pattern in capillaroscopy, and lower esophageal dysmotility) were established as possible indicators for a scleromyositis diagnosis [ 122 ].…”