Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Anti-SRP Auto-Antibody Titers Correlate with Serum Creatine Kinase in Necrotising Myopathy.
Benveniste1, Olivier, Drouot3, Laurent, Jouen3, Fabienne, Herson2, Serge, Charuel2, Jean-Luc, Bloch2, Coralie, Behin2, Anthony
Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, France
Inserm, U905, Rouen University, France
Rouen University Hospital, Department of Internal Medicine, France
Anti-signal recognition particle (SRP) auto-antibodies (aAbs) are associated with severe, generally treatment-resistant forms of acquired necrotising myopathies. The physiological role of the SRP complex is to guide the translocation of nascent polypeptides into the endoplasmic reticulum during protein synthesis. Since the expression of SRP is ubiquitous, the role of anti-SRP aAbs in myopathies remains elusive. Notably, clinical studies have been hampered by the lack of a quantitative assay for the longitudinal follow-up of anti-SRP aAb titers. To this end, we developed a Luminex-based quantitative test of anti-SRP aAb, referred to as Fluorescence Microsphere Immunoassays for quantification of SRP54-specific aAb (FMI-SRP54), and asked whether there was a correlation between anti-SRP aAb titers and serum creatine kinase (CK) levels.
The diagnostic value of the test was determined by comparing serum titers from 31 anti-SRP aAb positive patients to that of 190 healthy blood donors and 167 control patients with different inflammatory/autoimmune conditions including 80 rheumatoid arthritis, systemic sclerosis or lupus, 30 anti-tRNA synthetase aAb positive myositis, 30 inclusion body myositis and 27 patients with polyclonal hypergammaglobulinemia. Among the 31 anti-SRP aAb positive patients, 8 were sampled over time for monitoring of anti-SRP aAb titers and CK levels (at least 3 times consecutively with a mean follow-up of 722 days). The date of the first sample corresponded to the initiation of treatment (for naive patients) or restart of a modified one (for relapsing patients). The relationship between anti-SRP aAb titers and CK levels was tested using a linear mixed model.
The specificity of the assay was 100% with a confidence interval of [98%100%] and the sensitivity was 100%[89%100%]. There was a clear predominance of the IgG1 and IgG4 isotypes among anti-SRP54 aAbs. FMI-SRP54 permitted to measure the degree of aAb depletion after plasma exchanges that repeatedly reduced anti-SRP54 aAb titers by more than 2-fold in one patient studied. Importantly, the longitudinal follow-up of the 8 patients revealed a striking correlation between the degree of myolysis under therapy measured by CK levels and the anti-SRP54 aAb titers (p<0.005).
Anti-SRP aAb positive myopathy appears as one of the few human autoimmune diseases in which specific aAb titers correlate with surrogate disease activity markers. These results may also suggest a pathogenic role for anti-SRP aAbs and prompts to evaluate B-cell targeting therapies in patients with this particular form of necrotising myopathy.
To cite this abstract, please use the following information:
Benveniste, Olivier, Drouot, Laurent, Jouen, Fabienne, Herson, Serge, Charuel, Jean-Luc, Bloch, Coralie, et al; Anti-SRP Auto-Antibody Titers Correlate with Serum Creatine Kinase in Necrotising Myopathy. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :915