mTORC1 signaling in granulomatous lesions is not specific for sarcoidosis

Introduction: Linke et al. were the first to show the role of the metabolic checkpoint kinase: mechanistic (formerly mammalian) target or rapamycin complex 1 (mTORC1) in granuloma formation of sarcoidosis. This role was partly confirmed by a recent study of Pizinni et al. with, however, a clear discrepancy between the percentage of positive patients. Since sarcoidose is not the only disorder characterized by granulomas, we investigated the specificty of mTORC1 regarding multiple granulomatour disorders. Material and methods: Tissue of 74 sarcoidosis patients, 29 patient with hypersensitivity pneumonitis (HP), 7 patients with granulomatosis with polyangiitis (GPA) and 1 patient with eosinophilic granulomatosis with polyangiitis (EGPA) were collected. Tissue sections were stained with anti-p-S6 antibody; a hallmark of mTORC1 activiation. Baseline diagnostic tests, histopathological results and clinical findings were recorded. Results: In the sarcoidosis group, 45.9% showed to have p-S6 expression within the granulomas. of the positive group, 67.6% had progressive disease with need for therapy, versus 62.5% of p-S6 negative sarcoidosis patients. Furthermore, 38.5% of patients with HP/(E)GPA also showed p-S6 expression (p=0.447). Conclusion: Expression of mTORC1 with granulomas is not specific for sarcoidosis. Furthermore, in patient with sarcoidosis as well as HP/(E)GPA activation of mTORC1 was seen in less than half of the patients, which, regarding sarcoidosis, is not in line with the findings of Pizinni et al. Finally, mTORC1 activation was not associated with disease seviry nor with necessity of treatment. demonstrating a need for consensus on the interpretation of mTORC1 activation in biopsy material.