An Italian Multicenter Study on Anti-NXP2 Antibodies: Clinical and Serological Associations

Abstract

The identification of anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some reports, with cancer. Historically, these associations with anti-NXP2 antibodies have been detected by immunoprecipitation (IP), but in the last few years commercial immunoblotting assays have been released. The aim of this collaborative project was to analyse the clinical features associated to anti-NXP2 antibodies, both with commercial line blot (LB) and IP. Myositis-specific and myositis-associated autoantibodies were detected in single centres by commercial line blot (LB); available sera were evaluated in a single centre by protein and RNA immunoprecipitation (IP), and IP-Western blot. Sixty patients anti-NXP2+ (NXP2+) positive by LB were compared with 211 patients anti-NXP2 negative with idiopathic inflammatory myositis (IIM). NXP2+ showed a younger age at IIM onset (p = 0.0014), more frequent diagnosis of dermatomyositis (p = 0.026) and inclusion-body myositis (p = 0.009), and lower rate of anti-synthetase syndrome (p < 0.0001). As for clinical features, NXP2+ more frequently develop specific skin manifestations and less frequently features related with overlap myositis and anti-synthetase syndrome. IP confirmed NXP2 positivity in 31 of 52 available sera (62%). Most clinical associations were confirmed comparing NXP2 LB+/IP+ versus NXP2-negative myositis, with the following exceptions: inclusion-body myositis diagnosis was not detected, whilst dysphagia and myositis were found more frequently in NXP2 LB+/IP+ patients. The 21 LB+ /IP-myositis patients did not show differences in clinical features when compared with the NXP2-myositis patients and more frequently displayed multiple positivity at LB. Risk of developing cancer-associated myositis was similar between NXP2-positive and NXP2-negative myositis patients, either when detected by LB or IP. Protein-IP confirmed NXP2 antibodies in nearly 60% of sera positive for the same specificity with commercial assay. Double-positive cases rarely occurred in myositis patients with a clinical diagnosis other than dermatomyositis. Patients only positive by LB (LB+/IP−) did not display clinical features typical of NXP2. NXP2 positivity by LB should be confirmed by other methods in order to correctly diagnose and characterize patients affected by idiopathic inflammatory myositis.

Update on autoantibodies and related biomarkers in autoimmune inflammatory myopathies

“…In another study of anti-small ubiquitin-like modifier activating enzyme (SAE) in suspected inflammatory myositis [ 46 ], a higher cut-off on LIA >=36 units) yielded better agreement with IP. Similar limitations and approaches to LIA testing of anti-melanoma differentiation-associated protein (MDA5), anti-NXP2 (nuclear matrix protein) and anti-TIF1-γ (transcriptional intermediary factor) were reported by others [ 47 , 48 , 49 ▪ , 50 , 51 ]. A study of anti-HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) antibodies showed that detection of anti-HMGCR autoantibodies using LIA had high estimated clinical sensitivity and good concordance with an in-house laboratory developed ELISA [ 52 ].…”

Clinical, histologic and prognostic features of clinically amyopathic dermatomyositis

“…However, in patients with CADM, we did not observe an increased prevalence of cancer, underscoring the notion that cancer screening should be conducted in all patients with DM, regardless of their clinical presentation or autoantibody profile. Finally, all patients with anti-NXP2 or -Mi-2 antibodies exhibited muscle involvement, which should always be investigated and treated in these subclasses of DM frequently characterised by severe muscle involvement (14,17,18).The primary factors affecting prognosis in DM patients, independently from other serological and clinical features, appear to be ILD and cancer, without differences among DM, HDM, and CADM. The latter finding was unexpected as CADM showed a higher prevalence of lung involvement and it might be due to unknown confounding factors or the small sample size.…”

Profile of specific and associated autoantibodies in patients with idiopathic inflammatory myopathies in a Colombian population

“…It was found to be the only positive antibody in a patient with skin involvement. NXP2-positive cases have been reported to more frequently show typical manifestations of facial DM as a heliotrope rash ( p < 0.0001; OR 3.4, 95% CI 1.88–6.2) ( 49 ). Like many MSAs, its prevalence is highly variable, as is its association with the development of cancer ( 35 , 42 ).…”