Combinations of scleroderma hallmark autoantibodies associate with distinct clinical phenotypes

Abstract

Systemic sclerosis (SSc) is characterized by the presence of SSc-specific or SSc-associated antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (U3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/To (Th/To), each being associated with specific clinical features and prognosis. The detection of more than one SSc-Abs in SSc patients is rare and only few data about these patients’ clinical phenotype is available. The aim of our study was to evaluate the frequency and the disease’s features associated with the presence of > 1 SSc-Abs positivity in a large cohort of SSc patients. The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with > 1 SSc-Abs were identified. Clinical features were collected and compared to a large historical cohort of SSc patients with single SSc-Ab positivity. SSc patients were excluded if previously treated with rituximab, intravenous immunoglobulins or stem cell transplantation. Non-parametric tests were used for statistical analysis. Nearly 5% of SSc patients from our cohort had ≥ 2 autoantibody positivity, and 2.3% (n = 72) had ≥ 2 SSc-Abs positivity. Th e most common combination was U1RNP and ATA (35%). These patients were younger than patients with single autoantibody positivity and showed more commonly a diffuse cutaneous SSc form. They also had higher rates of overlap features compared to ATA patients. Other combinations included U1RNP and ACA (13%), ATA and ACA (7%) and U1RNP and PmScl (5%). In our study we observed that, while infrequently, SSc patients can present with a combination of two SSc-Abs and that the double positivity can influence their clinical phenotype compared to patients with single SSc-Ab positivity. The importance of re-testing SSc-Abs in patients with changing clinical phenotypes was also highlighted, as this may confer a differing risk stratification.

Release of High-Mobility Group Box-1 after a Raynaud’s Attack Leads to Fibroblast Activation and Interferon-γ Induced Protein-10 Production: Role in Systemic Sclerosis Pathogenesis

“…As in many autoimmune diseases, SSc patients are often characterized by disease-specific autoantibodies including anti-scl70, anti-centromere, anti-RNA polymerase III autoantibodies and others [ 28 ]. Although these autoantibodies have been associated with specific clinical manifestations and used as prognostic biomarkers, little is known about their pathogenetic mechanisms [ 29 ]. Recently, Raschi et al [ 30 ] have studied the pathogenetic effects of SSc-specific autoantibodies on endothelial cells.…”

Biomarkers in the Pathogenesis, Diagnosis, and Treatment of Systemic Sclerosis

“… 32 For instance, a recent study by Clark et al demonstrated that only 5% of SSc patients had ≥2 any autoantibody positivity and only 2.3% had ≥2 SSc-specific antibody positivity, with the most common combination being anti-U1RNP and anti-topoisomerase I antibodies. 33 …”

Systemic sclerosis following COVID-19 infection with recurrent corticosteroid-induced scleroderma renal crisis

“…7 Immune dysregulation resulting in autoantibody production is the serological hallmark of SSc with autoantibodies observed in 95% of cases. 8 The most frequent antibodies include anti-topoisomerase-1 (20%-45%), anti-centromere (12%-44%) and anti-RNA-polymerase III (5%-31%). 9 Antitopoisomerase-1 positivity is seen more frequently with diffuse subtype SSc, with patients typically displaying increased disease activity with more extensive skin involvement, with an increased risk of developing ILD.…”

“…Immune dysregulation resulting in autoantibody production is the serological hallmark of SSc with autoantibodies observed in 95% of cases 8. The most frequent antibodies include anti-topoisomerase-1 (20%–45%), anti-centromere (12%–44%) and anti-RNA-polymerase III (5%–31%) 9.…”