The utility of comprehensive autoantibody testing to differentiate connective tissue disease associated and idiopathic interstitial lung disease subgroup cases

Abstract

Interstitial lung disease (ILD) comprises many heterogeneous disease groups, the largest being CTD-associated and those labelled as idiopathic out of necessity. The mechanisms causing ILD are poorly understood, but most CTD- and idiopathic-ILD cases can respond to immunosuppression, clearly suggesting a pathological role for inflammation. By contrast, corticosteroid immunosuppression causes harm without benefit in the feared idiopathic pulmonary fibrosis, suggesting that inflammation plays little pathological role, and where ILD progresses rapidly to lethal outcome even with anti-fibrotic drug use. Given the treatment response differences apparent between ILD subgroups, and the dangers and costs of corticosteroid and anti-fibrotic drug use, respectively, it has become vital in every ILD patient to make an accurate subgroup diagnosis, to optimize treatment selections. This review discusses why differentiating CTD- and idiopathic-ILD subgroup cases remains so problematic, and why existing comprehensive CTD-specific serology would, if generally available, represent an ideal biomarker tool to enhance ILD subgroup diagnostic accuracy.

Keywords: anti-synthetase syndrome; antibodies; biomarkers; connective tissue disease; interstitial lung disease; myositis; serology.

Fig. 1

A classification of ILD into groups and subgroups The IPF and RA-ILD (UIP) subgroups are formatted left in each box, and made bold, to highlight that these ILDs exhibit similar fibrotic HRCT patterns (UIP) and are similarly treatment-resistant, with rapid progression to lethal outcomes within only 3–5 years of ILD onset. In contrast, and formatted to the right in each box, the other IIP and CTD-ILD subgroups, the latter including RA-ILD (non-UIP), show varying degrees of cellularity (i.e ground glass) on HRCT, and are usually responsive to immunosuppression to some extent. IPF: Idiopathic Pulmonary Fibrosis, ILD: Interstitial Lung Disease, UIP: Usual Interstitial Pneumonia, HRCT: High Resolution Computed Tomography, IIP: Idiopathic Interstitial Pneumonia. (Adapted from Ryerson CJ, Collard HR. Update on the diagnosis and classification of ILD. Curr Opin Pulm Med 2013;19:453–9).