WITHDRAWN: Characterization of Interstitial Lung Disease Subtypes by Bronchoalveolar Lavage Cytokine Profiles: A Cluster-Based Approach.

OBJECTIVE

To identify subgroups of ILD based on BALF cytokine profiles using cluster analysis and explore their clinical relevance and relationship with traditional disease classification, with particular focus on rheumatoid arthritis-associated ILD (RA-ILD).

METHODS

We reanalyzed the BALF cytokine dataset. BALF samples were collected from 84 patients with various types of ILDs, including 14 with IPF, 18 with NSIP, 6 with organizing pneumonia, 17 with sarcoidosis, 19 with myositis-associated ILD, and 10 with RA-ILD. A multiplex bead assay was used to measure the levels of the 17 cytokines. Cluster, principal component, cosine similarity, and discriminant analyses were performed to identify cytokine-based subgroups and investigate their clinical associations.

RESULTS

Three distinct cytokine clusters were identified: Cluster 1, characterized by high cytokine levels; Cluster 2, moderate levels; and Cluster 3, low expression. Cluster 1 was associated with a poor prognosis, whereas Cluster 3 was associated with favorable outcomes. No significant associations were found between the clusters and traditional disease classifications, except for cluster 3 and sarcoidosis. RA-ILD cases mainly appeared in Clusters 1 and 2, together with other ILDs, except sarcoidosis, and exhibited cytokine profiles similar to usual interstitial pneumonia IPF/NSIP. However, RA-ILD was uniquely characterized by elevated interleukin-17 and granulocyte-macrophage colony-stimulating factor levels, setting it apart from IPF/NSIP.

CONCLUSIONS

BALF cytokine profiling identified prognostically relevant ILD subgroups, independent of the traditional classification. RA-ILD shares cytokine profiles with IPF/NSIP but also exhibits distinct signatures. These results suggest that intrapulmonary cytokine profiling could serve as a tool for ILD stratification.