Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy

Abstract

Objective. Anti-signal recognition particle (anti-SRP) autoantibodies are associated with severe acquired necrotizing myopathies. The role of these autoantibodies remains elusive, and the evolution of anti-SRP levels over time is unknown. In this study, we developed an addressable laser bead immunoassay (ALBIA) technique to investigate a correlation between anti-SRP levels, serum creatine kinase (CK) levels, and muscle strength in patients with necrotizing myopathy.Methods. The diagnostic value of the ALBIA assay was determined by comparing serum levels of anti-SRP autoantibodies in 31 anti-SRP immunodotpositive patients to those in 190 healthy blood donors and 199 control patients with different inflammatory/ autoimmune conditions or polyclonal hypergammaglobulinemia. Among the 31 anti-SRP-positive patients, serum samples from 8 patients were monitored over time for levels of anti-SRP autoantibodies and levels of CK (determined at least 3 times, consecutively, over a mean followup period of 783 days). The relationship between levels of anti-SRP autoantibodies and levels of CK was tested using a linear mixed model.Results. The assay yielded positive results for anti-SRP in all anti-SRP immunodot-positive serum samples tested, while all control sera tested negative. The 8 anti-SRP-positive patients who were followed up longitudinally were found to have normalized CK levels and improved muscle strength. There was a striking correlation between the degree of myolysis, as measured by CK levels, in patients receiving therapy and the anti-SRP54 autoantibody levels in these same patients (P ‫؍‬ 0.002).Conclusion. Anti-SRP-positive myositis appears to be one of the few autoimmune diseases in which specific autoantibody levels are correlated with surrogate disease activity markers. These results reveal the usefulness of monitoring anti-SRP autoantibody levels in patients receiving therapy, and may also suggest a possible pathogenic role for anti-SRP autoantibodies in the necrotizing myopathies.Autoantibodies directed against signal recognition particles (anti-SRP) are present in a minority (4-6%) of patients with acquired inflammatory and/or necrotizing myopathies (1-5). Anti-SRP autoantibodies are generally associated with severe clinical forms of the disease, particularly those with heart and lung involvement (6,7) and resistance to steroid therapy (8-10).

Treatment and outcomes in necrotising autoimmune myopathy: An Australian perspective

“…In contrast, the connective-tissue disease associated patients had relatively preserved power and lower CK levels. These findings are all consistent with previous studies, with the anti-SRP subgroup tending to have the most severe weakness and statin-naïve anti-HMGCR positive patients having CK levels disproportionately high for the weakness severity (1,16,18). Our entire cohort received serological testing and all but one patient had a muscle biopsy performed, with only four patients without either positive anti-SRP or anti-HMGCR serology.…”

“…This supports the recently published diagnostic algorithm by Mammen et al, [14] which recommends serological testing for anti-HMGCR antibodies prior to muscle biopsy. Given the specificity of positive anti-HMGCR antibodies for NAM in the context of patients over 50 years with previous stain exposure [6,18,19], perhaps future diagnoses could be based on clinical picture and serology alone, without the need for invasive muscle biopsies. All patients were screened clinically for malignancy and 40% of our cohort received formal malignancy screening including either PET or CT imaging of chest, abdomen, pelvis, although no patients were found to have malignancy.…”

Expression of anti-SRP19 antibody in muscle tissues from patients with autoimmune necrotizing myopathy

“…Currently, expression of serum SRP is extensively researched in both domestic and international studies (Benveniste et al, 2011;Fernandez et al, 2013;Hanisch et al, 2013;Wang et al, 2014). It has been demonstrated that serum anti-SRP antibody is closely associated with autoimmune necrotizing myopathy (Picard et al, 2016).…”

“…We also found that anti-SRP19 antibody expression in muscle tissue of autoimmune NM patients has no apparent association with patient gender, age, duration, tension, creatine kinase, and other myositis-related antibodies. Benveniste et al (2011) quantitatively measured the level of anti-SRP antibodies in 8 cases of anti-SRP antibody-positive patients before and after glucocorticoid and immunosuppressive therapy, and found that serum CK and anti-SRP antibody concentrations decreased with improved symptoms before and after treatments (Stone et al, 2007;Mohassel and Mammen, 2013). Recent studies have confirmed that improvement of symptoms and remission of necrotizing myopathy is associated with returning of anti-SRP antibody to normal levels.…”

Paraneoplastic necrotizing myopathy in association with metastatic malignant melanoma: two case reports and a review of the literature

“…Anti-SRP subjects have unique clinical features, including more severe myopathy with dysphagia, very high CK levels, and better response to steroid therapy [3] . Two recent case series have suggested that anti-SRP levels do correlate with disease severity, and may serve as a marker of poor prognosis [13,14] . Additionally, a recent study identified anti-HMGCoA reductase autoantibodies in 63% of patients with necrotizing autoimmune myopathy [15] .…”