Background/Purpose:  Routine screening for circulating autoantibodies (AAbs) on the initial evaluation of interstitial lung disease (ILD) contributes to the diagnosis of underlying autoimmune disease. However, so far, few studies have focused on the role of AAbs as an independent prognostic factor in ILD, with conflicting results. In the present study, we investigated the possible association of AAbs with functional or radiological progression and survival in patients with ILD.

Methods: We retrospectively reviewed the medical records of patients with ILD followed up in a rheumatology and a respiratory outpatient clinic. Regular clinical, functional and computed tomography (CT) imaging follow-up for at least 2 consecutive years and complete testing for a panel of AAbs most commonly associated with ILD [such as antinuclear antibodies (ANAs) (positive titers ≥1:160), AAbs to extractable nuclear antigens, anti-neutrophil cytoplasmic antibodies, rheumatoid factor or anti-citrullinated protein antibodies] were our inclusion criteria. Eligible patients were subsequently classified into two groups: those without AAbs [ILD/AAb(-)] and those with positive ANAs and/or other specific AAbs, either with or without clinical manifestations compatible with connective tissue disease (CTD) [ILD/AAb(+)]. Serial pulmonary function tests (PFTs), including measurements of forced vital capacity [FVC (% pred.)] and single-breath diffusion capacity [DLCO_SB (% pred.)], degree of dyspnea according to modified MRC scale (mMRC) (Grade 0 to 4), baseline and comparative follow-up high resolution CT (hrCT) findings and survival data were also collected. Progression of lung disease on PFTs was defined as a sustained decrease from baseline in absolute FVC of ≥10% and/or absolute DLCO_SB of ≥15%. DLCO_SB<40% pred. on at least two consecutive measurements and disease progression on hrCT were defined as secondary endpoints.

Results:  Among 185 patients with ILD initially screened, 78 met our inclusion criteria. Fifty three of them were ILD/AAb(+) and 45 had a definite diagnosis of CTD. Mean age at first outpatient visit was 57.8 years and mean duration of follow-up was 72.6 months. ILD/AAb(+) patients were predominantly female (77% vs 28%), were significantly younger (54.2 ± 15.1 vs 65.6 ± 13.0 years), and had longer duration of follow-up (84.5 ± 58.1 vs 47.5 ± 29.6), compared with ILD/AAb(-) patients (p<0.01 for each comparison). Baseline FVC (% pred.) and DLCO_SB (% pred.) did not differ significantly between the two groups. During follow-up, mortality rates and the percentage of patients with sustained FVC or DLCO_SB decline, DLCO_SB <40% pred., or severe dyspnea (Grade 3-4) were lower in the ILD/AAb(+) group (p<0.05 for each). In addition, rates of radiological deterioration were marginally significantly lower (p=0.079). In Cox regression for survival analysis, AAb positivity was also associated with a reduced adjusted hazard ratio for death, PFT decline (p<0.001 for each outcome), and radiological deterioration (p=0.036).

Conclusion:  The presence of positive AAbs in patients with ILD is associated with better survival, less rapid decline of lung function and slower progression of CT findings.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prognostic-significance-of-autoantibody-positivity-in-interstitial-lung-disease-a-retrospective-case-control-study/