Molecular markers of disease in rheumatoid arthritis associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF)
| Observation in RA-ILD | Observation in IPF | |
| Telomere length | Shortened telomeres associated with RA-ILD and associated with worse survival [8, 79] | Shortened telomeres associated with IPF and associated with worse survival [62, 78] |
| MMP-7 | Differentiates RA-ILD from RA without ILD and correlated with worse pulmonary function and diffusing capacity [88] | Differentiates IPF from controls and correlated with worse pulmonary function and diffusing capacity [83-85] |
| ACPA | Differentiates RA-ILD from RA without ILD and correlated with worse pulmonary function and diffusing capacity [64-67] | Higher rates in IPF than seen in controls [92], unclear association with pulmonary function |
| IP-10/CXCL10 | Differentiates RA-ILD from RA without ILD and correlated with worse pulmonary function and diffusing capacity [88] | Not reported in IPF; currently under investigation as therapeutic target, given effects seen in murine models of IPF [107] |
| Rheumatoid factor | Levels of rheumatoid factor increased in RA-ILD when compared to RA without ILD; with higher levels in subclinical lung disease than clinically evident RA-ILD [24] | Not reported in IPF |
| SP | SP-D differentiates RA-ILD from RA without ILD as a part of a diagnostic model when combined with MMP-7, PARC and clinical risk factor score [24] | SP-A/D differentiate IPF from normal controls and correlated with worse survival [108] |
| KL-6 | Associated with deterioration in RA-ILD; additionally, KL-6 levels decreased with successful treatment of RA-ILD, indicating possible role of KL-6 as a theragnostic biomarker [109] | Elevated KL-6 levels in IPF were associated with poorer prognosis; serial increases in KL-6 portend more rapid decline in pulmonary physiology and increased mortality [110] |
| CCL-18 | CCL-18 levels higher in the BALF of RA-ILD subjects than controls, and CCL-18 levels in BALF predicted mortality during hospitalisation [111] | Baseline levels of CCL-18 predicted decline in FVC and DLCO at 6 months and baseline CCL-18 level in IPF correlated with worse survival [112] |
| LOXL2 | Serum LOXL2 levels in RA-ILD higher than those in control subjects; LOXL2 was highest in those RA-ILD patients with shorter duration of lung involvement (<3 months compared to >3 months) and LOXL2 was correlated with worse FVC and DLCO [113] | In IPF cohorts, higher serum LOXL2 levels were correlated with worse pulmonary physiology and greater risk for mortality and disease progression [114] |
| Periostin | Not reported in RA-ILD | Associated with IPF disease progression [115] |
| IL-8 | Not reported in RA-ILD | Correlated with worse FVC and DLCO and predicts disease activity [116] |
| HSP | Autoantibodies to HSP-90 differentiated RA-ILD from IPF and differentiated RA-ILD patients from RA patients without ILD, unclear association with disease activity [117] | Patients with IPF who have autoantibodies to HSP-70 have worse near-term decline in FVC and DLCO and worse mortality [118] |
| CXCL-13 | Not studied in RA-ILD | Higher levels of CXCL-13 in IPF are associated with worse prognosis [119] |
| CA-125 | Differentiates RA-ILD patients from RA without ILD patients; not clear if has prognostic ability in RA-ILD [120, 121] | Differentiates IPF from CTD-ILDs; correlated with disease progression and worsened survival; associated with lung cancer in IPF [122, 123] |
| YKL-40 | Not studied in RA-ILD | Differentiates IPF patients from controls and idiopathic NSIP, serum and BALF levels associated with worsened survival [124, 125] |
MMP: matrix metalloproteinase; ACPA: anti-citrullinated protein antibodies; IP: interferon-γ induced protein; CXCL: C-X-C motif chemokine; SP: surfactant protein; KL: Krebs von den Lungen; CCL: C-C chemokine ligand; LOXL: lysyl oxidase-like; IL: interleukin; PARC: pulmonary and activation-regulated chemokine; BALF: bronchoalveolar lavage fluid; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; HSP: heat shock protein; NSIP: nonspecific interstitial pneumonia; CTD-ILD: connective tissue associated interstitial lung disease.