Anti-PL-7/PL-12 antisynthetase syndrome associated with interstitial lung disease following SARS-COV-2 infection and vaccination: A case study review

Abstract

Cumulative evidence suggests a link between specific autoimmune diseases (AD), including idiopathic inflammatory myopathies (IIM), and SARS-CoV-2 infection or COVID-19 vaccination. Anti-synthetase syndrome (ASS), a subset of IIM, is defined by the presence of autoantibodies against aminoacyl-tRNA synthetase (anti-ARS) and is strongly associated with interstitial lung disease (ILD), a major contributor to severe complications and reduced survival. We present four clinical cases of patients who developed autoantibodies against threonyl (PL-7) and alanyl (PL-12) synthetases associated with ASS-ILD shortly after SARS-CoV-2 infection or COVID-19 vaccination. Anti-ARS autoantibodies were identified using three complementary methods: immunoblotting, western blotting (WB) and the method considered the gold standard, immunoprecipitation (IP), which ensures accurate interpretation of results. The study highlights the clinical and pathogenic overlap between ASS-ILD and SARS-CoV-2-related lung involvement.Both conditions share similar high-resolution computed tomography (HRCT) patterns, including inflammation and pulmonary fibrosis (PF), driven by IFN-γ signaling, which complicates accurate diagnosis. Our results provide novel insights into the temporal association of SARS-CoV-2 and vaccine exposure with ASS-ILD, focusing on possible molecular mimicry between viral proteins and ARS molecules as a potential mechanism. Understanding the involvement of specific anti-ARS autoantibodies (PL-7 and PL-12) and the identification of genetic predispositions (HLA-B∗08:01 and HLA-DRB1∗03:01) in these patients may be key to underpinning these autoimmune manifestations. The study underscores the importance of a multidisciplinary approach and vigilant follow-up to optimize diagnosis and management. Further research is essential to elucidate the causal relationships and molecular mechanisms behind these observations.

Keywords: Anti-synthetase syndrome; COVID-19; Idiopathic inflammatory myopathies; Interstitial lung disease; SARS-CoV-2 vaccine.

Fig. 1

Indirect immunofluorescence (IIF) on Hep-2 cells. Fine dense cytoplasmic mottled pattern (AC-19) at 1:640 titer in serum from reported cases Nº1 (A) and Nº3 (B).

Fig. 2

Results for anti-PL-12 autoantibodies detection in patients Nº1 and Nº3. Anti-PL-12 autoantibodies were detected by commercial immunoblot and evaluated automatically with the EUROLineScan software showing results of very strong intensity (+++) (A). Anti-PL-12 autoantibodies of both patients were confirmed by western blotting (WB) using recombinant protein of human alanyl-tRNA synthetase (B). Gold standard RNA immunoprecipitation (IP) technique for detection of tRNA synthetases in native form with migration in the lower zone of the agarose gel. Samples from patients Nº1 (lane A) and Nº3 (lane B) show bands compatible with PL-12 tRNA synthetase. Serum from patient without known autoantibodies is used as a negative control (lane C) and serum from patient with known anti-PL12 autoantibodies is used as a positive control (lane D) (C).

Fig. 3

High-resolution computed tomography (HRCT) chest findings from patient Nº 1. Fibrotic NSIP pattern: The results show bilateral and symmetric interstitial lung involvement, predominantly in both lung bases. The involvement consists of bronchiectasis and cylindrical bronchiectasis, as well as septal thickening and faint ground-glass attenuation opacities.

Fig. 4

Chest X-ray findings from patient Nº2. Results showed patchy bilateral alveolar consolidations (A). Subsequent results demonstrated resolution of previous pulmonary infiltrates (B).

Fig. 5

High-resolution computed tomography (HRCT) chest findings from patient Nº 2. Organizing pneumonia pattern: The results show subtle areas of ground glass attenuation in the lower lobes and a small consolidation area of nodular morphology with air bronchogram in the right basal pyramid.

Fig. 6

Results for anti-PL-7 autoantibodies detection in patients Nº2 and Nº4. The analytical methods used were the same as for the detection of anti-PL12 antibodies. Anti-PL-7 autoantibodies were detected by commercial immunoblot showing results of medium and low intensity (++/+) (A). Anti-PL-7 autoantibodies of patient Nº2 were not confirmed by WB, however the result was positive in patient Nº4 (B). Patient samples Nº2 (lane C) and Nº4 (lane D) show no bands compatible with anti-PL-7 antibodies by IP. Lane A shows a serum from a patient with known anti-PL-7 autoantibodies used as a positive control and lane B shows a serum from a patient without known autoantibodies as a negative control (C).

Fig. 7

High-resolution computed tomography (HRCT) chest findings from patient Nº 3. Fibrotic NSIP pattern: The results display a bilateral and symmetrical reticular interstitial pattern with a subpleural distribution and bibasal predominance. The condition is characterized by thickening of the inter- and intra-lobular septa, bronchiectasis and traction bronchiolectasis, with a bibasal predominance.