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Transcriptomic Profiling and Drug Repurposing Identify Fostamatinib as a Candidate Therapeutic Agent for IgG4-Related
Motohisa Yamamoto1, Ryuta Kamekura2, Masaaki Uehara1
1Department of Rheumatology, Allergy and Clinical Immunology, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Objectives:
To identify therapeutic candidates for IgG4-related sialadenitis, a manifestation of IgG4-related disease characterized by IgG4-positive plasma cell infiltration and limited treatment options beyond glucocorticoids, using transcriptomic profiling and in silico drug repurposing.
Methods:
Submandibular gland tissues from 49 patients with IgG4-related sialadenitis and 3 controls were analyzed by RNA sequencing. Differentially expressed genes were screened against DrugBank to identify druggable targets. Candidate drugs were prioritized based on their ability to modulate disease-associated gene signatures. Molecular docking was performed to evaluate binding affinities to key targets.
Results:
Transcriptomic analysis revealed upregulation of immune-related pathways. DrugBank integration identified fostamatinib as a top candidate targeting multiple kinases, including SYK, BTK, and JAK3. Docking analysis demonstrated favorable binding affinity, particularly to BTK.
Conclusion:
This integrative approach highlights fostamatinib as a promising therapeutic candidate and supports a role for the SYK-BTK axis in IgG4-RD pathogenesis, suggesting a potential alternative to glucocorticoids.
