Background/Purpose:

Autoantibodies occur in 75-95% of Systemic Sclerosis (SSc) patients. Studies have shown that the presence of particular SSc-specific autoantibodies (anti-centromere, anti-topoisomerase-1, anti-RNA polymerase III, anti-U3RNP, anti-U11/U12 RNP and anti-To/Th) correlates with distinct clinical subsets of patients. Additionally, SSc-related autoantibodies (PmScl, Ku, Ro60, La and U1RNP) can be found in a variety of other connective tissue diseases including SSc patients with overlap features. However, despite this vast array of SSc associated autoantibodies, there still remains a minority of patients that appear to be autoantibody negative. Here we report a novel SSc-specific autoantibody in 7 SSc patients.

Methods:

Serum and clinical data were available from 379 patients with SSc investigated for interstitial lung disease (ILD) at the Royal Brompton Hospital and a separate 169 unselected SSc patients (Bath). Serum was also available from a control population consisting of 171 patients with other forms of connective tissue disease (dermatomyositis, polymyositis, systemic lupus erythematosus and rheumatoid arthritis), 141 patients with idiopathic ILD and 88 healthy normal controls. All sera were tested by routine serological techniques followed by radiolabelled protein immunoprecipitation (IPP) for samples negative for anti-centromere, anti-topoisomerase 1 and anti-RNA polymerase III. Patients’ sera immunoprecipiating a novel 30 kDa band were further analyzed by indirect immunofluorescence and IPP using depleted cell extracts, to establish a common reactivity. A combination of non-radiolabelled IPP and mass spectrometry (MS) was used to identify the novel autoantigen and findings were confirmed using a commercial antibody in both immunodepletion and IPP-western blotting assays.

Results:

A novel autoantigen at ~30 kDa was recognized by sera from 7 sera from patients with SSc and by no controls. None of the 7 positive sera contained other known SSc-specific autoantibodies, although one patient co-immunoprecipiated SSc-associated Ro60 autoantigens. All 7 sera resulted in a cytoplasmic speckled pattern on IIF. Immunodepletion experiments indicated that all 7 serum samples immunoprecipitated the same autoantigen and MS analysis identified the novel autoantigen as EIF2B (Eukaryotic Initiation Factor 2B, subunit β). These findings were confirmed by both IPP and IPP-western blotting using a commercial anti-EIF2B antibody. Clinically, 6 anti-EIF2B positive patients had confirmed ILD, whilst the 7^th patient did not have a chest CT, but had a reduced pulmonary gas transfer, demonstrating an association between anti-EIF2B and ILD (p=0.018). Six of the patients had diffuse cutaneous involvement (p=0.008) and four had overlap features with other autoimmune diseases (two polymyositis and two RA).

Conclusion:

We report the presence of SSc-specific autoantibodies to anti-EIF2B in approximately 1% of SSc / SSc overlap patients. These autoantibodies are associated with the presence of ILD and diffuse cutaneous disease, and may therefore act as a biomarker, aiding in the clinical diagnosis and treatment of this subset of patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-eif2b-a-novel-interstitial-lung-disease-associated-autoantibody-in-patients-with-systemic-sclerosis/