DISCORDANT FORMS OF INTERSTITIAL LUNG DISEASES IN MONOZYGOTIC TWINS: CASE REPORT

Abstract

Interstitial lung diseases (ILDs) - heterogeneous group of chronic progressive conditions with an unfavorable prognosis, in whose pathogenesis genetic susceptibility and environmental factors interact. Despite accumulating evidence regarding the role ofMUC5Bgene polymorphism in the development of IPF and HP, the mechanisms underlying the formation of different nosological and phenotypic ILD variants in individuals with an identical genetic background remain insufficiently understood. In this context, observations of monozygotic twins are of particular scientific and clinical value, as they allow assessment of the contribution of environmental and epigenetic factors to the development of phenotypic discordance. This article presents a clinical case of two monozygotic sisters born in 1957 with discordant forms of ILD. Both patients had similar antenatal and early postnatal characteristics, an identical rs35705950MUC5Bgenotype (GG), and a positive family history of chronic cough among first-degree relatives. However, their occupational, domestic, and environmental exposures differed substantially. In the first patient, who had long-term employment in an archive with potential exposure to dust and mold, MSCT revealed a UIP pattern with subpleural and basal predominance of fibrosis and traction bronchiectasis. According to TBB findings (2024), the morphological changes were consistent with acute interstitial pneumonia. FVC was 73% of the predicted value. The combination of clinical, radiological, and morphological findings in the absence of an identifiable etiology allowed the condition to be classified as IPF. In the second patient, who had prolonged exposure to domestic birds, MSCT demonstrated a predominance of ground-glass opacities with less pronounced fibrosis. FVC was 67% of the predicted value, and the clinical–radiological pattern corresponded to nonfibrotic HP with a progressive course. Additional assessment of pulmonary function parameters and carbohydrate metabolism did not reveal differences sufficient to explain the observed phenotypic discordance. This observation demonstrates that even in individuals with complete genetic identity carryingMUC5Brisk alleles, ILD may develop along different nosological pathways, highlighting the significant role of environmental exposures and, likely, epigenetic mechanisms in shaping ILD phenotypes.