D1.356 - Atypical association of anti-EJ and anti-RNA polymerase III antibodies in a patient referred for interstitial lung disease

Background

Interstitial lung disease (ILD) may contribute to the presentation of systemic autoimmune conditions such as the anti-synthetase syndrome (ASS), systemic sclerosis (SSc) or scleromyositis. The specificities of autoantibodies (aAb) and the associated clinical findings guide the diagnosis.

Case

A septuagenarian female patient was referred for etiological investigation of ILD with chronic respiratory failure requiring oxygen for the past three years. Notable medical history included heart failure due to hypertensive and arrhythmic cardiomyopathy, two ischemic strokes with resulting left hemiparesis and right hemiplegia, and gastro-esophageal reflux.

Clinical examination did not find evidence of systemic disease. There was no edema of the lower limbs, no finger clubbing, no digital fissure syndrome, no sclerodactyly, and no Raynaud's syndrome. The patient did not complain of joint pain or fever and skin examination was normal. Renal function and creatine kinase levels were normal.

Chest CT scan showed multiple hilar and mediastinal lymphadenopathy and diffuse interstitial lung fibrosis with peribronchovascular lesions, consolidations containing traction bronchiectasis, predominantly in the lower halves of the lungs, no reticulation and no honeycombing.

Line immuno-assays revealed high titers (3+) of anti-EJ (Glycyl-tRNA synthetase), anti-Ro52 and anti-RNA polymerase III (ARA) aAb (Euroimmun + Dtek) with consistent Hep2 nuclear (i.e fine-speckled nucleoplasmic stain with bright dots) and AC-19 cytoplasmic patterns.

Discussion

Anti-EJ Ab are part of the 23 specific Ab of ASS. Their presence, with ILD, fulfills the criteria necessary for the diagnosis of ASS according to the Connors 2010 classification but not according ACR/EULAR 2017 or any other classification. However, isolated ILD at disease onset is the most frequent presentation for anti-EJ Ab associated with nonspecific interstitial pneumonia. The positivity of Ro52 Ab argues in favor of ASS, as they are strongly associated with ASS, ILD, dysphagia, female predominance and with a decreased frequency of muscle involvement in an ASS cohort.

ARA are considered specific of systemic sclerosis (SSc) and were not reported with scleromyositis, which makes the anti-EJ - ARA association intriguing. However, heart involvement and ILD are associated with ARA positivity in SSc. Thus, this association of anti-EJ and ARA aAb constitutes a real diagnosis challenge.