The changing landscape of the clinical value of the PM/Scl autoantibody system

Abstract

Autoantibodies to the polymyositis/scleroderma (PM/Scl) complex have been associated with systemic sclerosis and PM/Scl overlap syndrome. The report of Hanke and colleagues in a recent issue of Arthritis Research and Therapy is the first to describe the separate evaluation of anti-PM/Scl-75c and PM/Scl-100 autoantibodies and their relationship to clinical manifestations of systemic sclerosis. Several observations are of paramount interest, but are not in general agreement with earlier studies. These include the prevalence of anti-PM/Scl antibodies in systemic sclerosis, the association with certain clinical manifestations and prognosis of patients. This report will hopefully trigger systematic multi-centre studies to confirm and/or elucidate the novel line immunoassay and clinical associations. BackgroundA characteristic feature of patients with systemic sclerosis (SSc; or scleroderma (Scl)) are anti-nucleolar antibodies (ANoAs), including autoantibodies (aabs) to components of the exosome, known also as the polymyositis/scleroderma (PM/Scl) complex [1,2]. While the majority of the anti-PM/Scl reactivity is directed against PM/Scl-75c and PM/Scl-100, many of the other nine core exosome components are also targeted, albeit with lower frequency and apparently limited diagnostic value [2]. Detection of PM/Scl antibodiesHistorically, anti-PM/Scl aabs were associated with PM/Scl overlap syndrome and were detected by indirect immunofluorescence (IIF) on HEp-2 cells, immunodiffusion, immunoblotting (IB), and/or immunoprecipitation. The clinical usefulness of PM/Scl aabs detected by IB and IIF was limited due to weak reactivity on IB and interference of other ANoAs in IIF. More recently, recombinant proteins (primarily PM/Scl-100) have been used as antigen targets in immunoassays, and a peptide-based PM1-Alpha enzyme-linked immunosorbent assay (ELISA) was reported to demonstrate higher sensitivity than traditional methods for the detection of anti-PM/Scl aabs [2][3][4]. Line immunoassays (LIAs), the precursor of today's more sophisticated multiplex assays such as addressable laser bead assays (ALBIAs), have become a popular technique for the simultaneous detection of aabs [5]. Several LIAs for the detection of PM/Scl aabs are available, covering a variety of myositis-and/or SSc-associated autoantigens; all of them using the PM/Scl-100 antigen to detect anti-PM/Scl reactivity [2]. With an increasing number of diagnostic platforms to test anti-PM/Scl reactivity, more diligent attention needs to be given to standardizing the autoantigens used in assays and the various platforms (LIA, ELISA, ALBIA) in which they are employed [5]. Major and early PM/Scl epitopeLike many aab responses, aabs to the PM/Scl macromolecular complex likely undergo intermolecular epitope spreading. For example, Gutiérrez-Ramos and colleagues [6] recently reported a patient with high anti-PM/Scl aab titres identified by IIF and confirmed by IB (100 kDa band). Three months later, the patient's serum contained aabs to another 39 kDa protein tha...

Autoantibody profile in a cohort of Algerian patients with systemic sclerosis

“…Comparable frequencies were observed in Caucasians but higher values were reported in Mexican patients [14,15,26]. Contrasting with previous studies, we did not find any significant association of these autoantibodies with disease subtype or specific clinical features [36,37]. Anti-SSA/Ro (Ro52 and Ro60) antibody was the second most common autoantibody (second to ATA) in our cohort with a prevalence of 32.7%.…”

Epitope specificity and significance in systemic autoimmune diseases

“…Of particular interest, the agreement between the ELISA with PM1‐α and PM/Scl‐100 was stronger in the group of PM/Scl‐overlap syndrome patients compared to the entire patient cohort, thereby indicating that anti‐PM1‐α aAbs show higher correlation to the overlap syndrome than aAbs to other epitopes of PM/Scl‐100. This observation was further supported by a study on anti‐PM/Scl‐75c and PM/Scl‐100 aAbs in SSc 125,126 …”

Autoantibodies in SLE: prediction and the p value matrix

“…the ''interferon signature'') and other proinflammatory mediators and AA changes that set the stage for progression to clinically overt disease. [45][46][47] In some individuals, the presence of an 30 Fritzler et al, 31 Mahler et al 32 and Yaniv et al 33 autoimmune signature may be limited to a transient or subclinical disease, whereas in others the disease progresses relentlessly, perhaps under the influence of a ''second hit'' by any number of endogenous or exogenous agents such as metabolic or physiologic stress and exogenous agents such as viruses, xenobiotics and toxins. 48 Efforts to determine whether AA predicted the onset of SLE were undertaken with compelling evidence that they predicted flares, remission, clinical outcome and/or prognosis in other autoimmune diseases.…”