Bench to bedside review of myositis autoantibodies

Abstract

Idiopathic inflammatory myopathies represent a heterogeneous group of autoimmune diseases with systemic involvement. Even though numerous specific autoantibodies have been recognized, they have not been included, with the only exception of anti-Jo-1, into the 2017 Classification Criteria, thus perpetuating a clinical-serologic gap. The lack of homogeneous grouping based on the antibody profile deeply impacts the diagnostic approach, therapeutic choices and prognostic stratification of these patients. This review is intended to highlight the comprehensive scenario regarding myositis-related autoantibodies, from the molecular characterization and biological significance to target antigens, from the detection tools, with a special focus on immunofluorescence patterns on HEp-2 cells, to their relative prevalence and ethnic diversity, from the clinical presentation to prognosis. If, on the one hand, a notable body of literature is present, on the other data are fragmented, retrospectively based and collected from small case series, so that they do not sufficiently support the decision-making process (i.e. therapeutic approach) into the clinics.

Patients with Interstitial Lung Disease Secondary to Autoimmune Diseases: How to Recognize Them?

“…Anti-Sm and Anti-RNP can be present in several CTDs, but are specific for SLE, while anti-U1-RNP is specific for MCTD [95]. Anti-RNP is generally associated with mild myositis and ILD [96]. Anti-SSA and anti-SSB are associated with SjS, but the latter antibody was excluded by new classification criteria for SjS [97].…”

“…Both are specific for SjS, but they can be found in several other CTDs, especially SSA52 kD, which is frequently associated with IIMs [96]. It should be taken into consideration that anti-SSA can be positive at ANA negative for the loss of anti-SSA60 kD during preparation, but also because SSA52 kD recognizes a cytoplasmic antigen [96]. SSA52 kD is mainly associated with ILD in both IIMs and SjS [69].…”

“…The ENA profile also includes anti-Jo1, the most frequent antisynthetase antibody and the unique one included in ENA commercial kits. It recognizes histidyl-tRNA synthetase, a cytoplasmic protein; therefore, similarly to anti SSA52 kD, it can be positive with ANA negative [96]. Anti-Jo1 is associated with arthritis, myositis, and ILD in IIMs and mainly ASS [100,101].…”

“…A number of other, generally rare, MSAs and MAAs can be associated with ILD, the largest part belonging to the family of IIMs [96].…”

The clinical spectrum of dermatomyositis and the new autoantibodies – with regard to two clinical cases with distinct associations

“…The cases described illustrate two of the typical phenotypes that have been identified in dermatomyositis. The first case with the presence of the anti‐MDA5 autoantibody which is characteristically related to pulmonary interstitial disease, that can be rapidly progressive and potentially fatal, especially in patients with higher anti‐MDA5 titres and when this autoantibody, is associated with anti‐Ro52, which was not the case in our patient. Unlike MDA5, the anti‐TIF1‐γ antibody protects against lung disease but, over 40 years, it has a strong correlation with the paraneoplastic form of dermatomyositis, as exemplified by the second case, in which dermatomyositis arose after tumour recurrence and worsened substantially after its massive metastization.…”