Serological Profile in Differentiating Interstitial Lung Disease (ILD) Subtypes: A report from Western India

ILDs are heterogeneous group of pulmonary disorders with overlapping clinico-radiological features, complicating ILD subtype diagnosis. Serological parameters may aid current diagnostic procedures for differentiating ILD-subtypes. This study aimed to conduct a comprehensive serological profiling of ILD patients from western India, to examine their subtype-specific expression.

In this cross-sectional study, ILD patients(n=200: CTD-ILD, IPF, idiopathic NSIP, fHP, and other ILDs), and healthy controls(n=40) were enrolled. 27 serum parameters were quantified using ELISA and multiplex immunoassays.

MMP7 levels were elevated in IPF vs CTD-ILD and fHP(14.01 vs 8.69 and 7.97ng/ml, p<0.05). The MMP7/TIMP1 ratio was highest in iNSIP vs fHP and CTD-ILD(0.10 vs 0.05 and 0.04, p<0.05). Anti-MDA5-Ab levels were elevated in CTD-ILD vs fHP and iNSIP(69.83 vs 46.71 and 51.21pg/ml, p<0.05). LDH levels were higher in CTD-ILD than iNSIP(38.76 vs 33.85pg/ml, p<0.05), while IL-22 was elevated in CTD-ILD vs fHP and IPF (4.94 vs 3.29 and 3.57pg/ml, p<0.05). Combined panels improved discrimination: IPF vs CTD-ILD (MMP7+MMP7/TIMP1+IFNγ+IL22, AUC=0.75, Sens=76.7%, Spec=72.2%), CTD-ILD vs fHP(MMP9+Anti-MDA5-Ab+IL22, AUC=0.803, Sens=84.1%, Spec=76.7%), CTD-ILD vs iNSIP(MMP1+MMP7+LDH+Anti-MDA5-Ab+MMP1/TIMP1+MMP7/TIMP1, AUC=0.805, Sens=69.5%, Spec=86.4%), and IPF vs fHP (MMP7+Anti-MDA5-Ab, AUC=0.719, Sens=50.0%, Spec=86.7%). PFT parameters were negatively correlated across ILD subtypes with disease duration, comorbidities, inflammatory markers, and cytokines, specifically, KL-6, IFN-γ, IL-22, and CIC-C1q.

This study provided a serological profile of an Indian ILD cohort that may support the differentiation of ILD subtypes alongside established diagnostic modalities. Further longitudinal studies on these serological parameters in ILD patients will strengthen the diagnostic perspective in the Indian clinical context.