Significance of Sjögren’s syndrome and anti-cN1A antibody in myositis patients

Abstract

Objective We recently recorded a high prevalence of inclusion body myositis (IBM) in patients with Sjögren’s syndrome (SS). Whether myositis patients with SS differ from myositis patients without SS in terms of the characteristics of the myositis is currently unknown. Anti-cytosolic 5’-nucleotidase 1 A (cN1A) has recently been proposed as a biomarker for IBM but is also frequent in SS. Whether anti-cN1A is independently associated with IBM is still an open question. We aimed to assess the significance of SS and anti-cN1A in myositis patients. Methods Cumulative data on all myositis patients (EULAR/ACR 2017 criteria) screened for SS (ACR/EULAR 2016 criteria) in a single center were analyzed. Ninety-nine patients were included, covering the whole spectrum of EULAR/ACR 2017 myositis subgroups and with a median follow-up of 6 years [range 1.0–37.5]. The 34 myositis patients with SS (myositis/SS+) were compared with the 65 myositis patients without SS (myositis/SS-). Results IBM was present in 24% of the myositis/SS+ patients vs 6% of the myositis/SS- group (p = 0.020). None of the IBM patients responded to treatment, whether they had SS or not. Anti-cN1A was more frequent in myositis/SS+ patients (38% vs 6%, p = 0.0005), independently of the higher prevalence of IBM in this group (multivariate p-value: 0.02). Anti-cN1A antibody specificity for IBM was 0.96 [95% CI, 0.87–0.99] in the myositis SS- group but dropped to 0.70 [95% CI, 0.48–0.85] in the myositis SS/+ group. Interpretation In myositis patients, SS is associated with IBM and with anti-cN1A antibodies, independently of the IBM diagnosis. As a consequence, anti-cN1A has limited specificity for IBM in myositis patients with SS.

Diagnostic and prognostic value of anti-cN1A antibodies in inclusion body myositis

“…SS has been shown to share common pathogenic mechanisms with IBM (22). In a recent study, IBM was diagnosed more freqeuntly in myositis patients with SS, than in myositis patients without SS (38). Although anti-cN1A seropositivity was more frequent in SS patients with concurrent myositis, this association between SS and anti-cN1A was shown to be independent from the diagnosis of IBM.…”

“…However, seropositivity in such conditions adds another layer of complexity when considering anti-cN1A as a diagnostic marker calling into question its specificity to IBM. In particular patients with Sjögren's syndrome (SS) and systemic lupus erythematous (SLE) have been shown to test positive for anti-cN1A antibodies fairly frequently (18,26,32,34,38,47). In the largest study investigating anti-cN1A positivity in SLE and SS, the frequency of seropositive patients ranged from 6 to Diagnostic and prognostic value of anti-cN1A antibodies in IBM / S. Salam et al…”

Inclusion body myositis: evolving concepts

“…An ongoing National Institute of Health-funded 2-year observational study is examining the influence of this serological biomarker on the natural history of IBM (NCT05046821). IBM is more common in Sjogren's syndrome patients with myositis and these patients have much higher rates of NT5c1A seropositivity [18].…”

Inclusion body myositis and Sjögren’s syndrome: the association works both ways

“…Secondly, discussing a study based on administrative data (ICD9 and ICD10), Nelke et al reported a more likely association of SjS with IBM over the other subtypes of myositis [ 6 ]. Further demonstrating this point, in an independent monocentric myositis cohort (ACR/EULAR criteria), deeply characterized at the clinical, serological and histopathological levels, covering the entire myositis spectrum and systematically screened for SjS (ACR/EULAR criteria), we showed that myositis patients with SjS more frequently present IBM than myositis patients without SjS (24% vs. 6% p = 0.02) [ 7 ].…”

“…Yet, we recently showed that in myositis patients, the association between anti-cN1A and SjS is independent of the association between IBM and SjS. Consequently, the specificity of anti-cN1A for IBM was excellent in myositis patients without SjS (0.96, 95% CI: 0.87, 0.99), but was limited in myositis patients with SjS (0.70, 95% CI: 0.48, 0.85) [ 7 ].…”