Anti-Myxovirus Resistance Protein-1 Immunoglobulin A Autoantibody in Idiopathic Pulmonary Fibrosis

Abstract

Background: We have previously analysed serum autoantibody levels in patients with idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), and healthy controls and identified the autoantibody against anti-myxovirus resistance protein-1 (MX1) to be a specific autoantibody in iNSIP. We found that a higher anti-MX1 autoantibody level was a significant predictor of a good prognosis in patients with non-IPF idiopathic interstitial pneumonias. In this retrospective study, we sought to clarify the prognostic significance of the anti-MX1 autoantibody in IPF.

Methods: We measured anti-MX1 immunoglobulin (Ig) G, IgA, and IgM autoantibody levels by enzyme-linked immunosorbent assay in serum collected at the time of diagnosis from 71 patients with IPF diagnosed according to the 2018 IPF guideline. The gender-age-physiology (GAP) index was calculated in each case.

Results: The study population (59 men and 12 women) had a median age of 67 years. Serum anti-MX1 IgG and IgA autoantibody levels correlated positively with GAP stage (p < 0.05). Univariate Cox proportional hazards regression analysis did not identify an elevated anti-MX1 IgG, IgA, or IgM autoantibody level as a significant prognostic factor; however, a higher anti-MX1 IgA autoantibody level heralded significantly poorer survival after adjustment for GAP stage (p=0.030) and for percent forced vital capacity and modified Medical Research Council score (p=0.018). Neither the anti-MX1 IgG autoantibody nor the IgM autoantibody could predict survival after these adjustments.

Conclusions: The serum anti-MX1 IgA autoantibody level is a significant prognostic factor in IPF. Further studies are needed to clarify the pathophysiological role of this autoantibody in IPF.

Figure 1

Survival (a) and incidence of acute exacerbation (AE) (b) in patients with idiopathic pulmonary fibrosis (IPF). Median survival time was 2079 days (a) and median interval from diagnosis to AE was 2707 days (b).

Figure 2

Survival (a) and incidence of acute exacerbation (b) in patients with idiopathic pulmonary fibrosis (IPF). Survival of IPF with higher levels (>0.312; n = 4, bold line) of serum anti-MX1 IgA autoantibody was significantly worse than that with lower levels (≤0.312; n = 67, dotted line) (log-rank test, p < 0.001). AE occurred significantly more frequently in IPF with higher levels of serum anti-MX1 IgA autoantibody (>0.312; n = 4, bold line) than in IPF with lower levels (≤0.312; n = 67, dotted line) (log-rank test, p=0.035).