OBJECTIVES: Smoking is recognised as one of the strongest environmental risk factors for the development of rheumatoid arthritis (RA). Cigarette smoke increases protein post-translational modifications (PTMs), including citrullination and carbamylation, involved in the pathogenetic mechanisms of RA. Recently, tobacco companies developed new products, such as iQOS, a heat-not-burn cigarette (HNBC), which are becoming increasingly used. To date, only two epidemiological studies have been conducted in the rheumatology field. However, no studies are available on the effects of HNBCs on the pathogenic mechanisms involved in rheumatic diseases. We aimed to evaluate whether HNBCs are associated with an increase in PTMs and their effects on cell death mechanisms, such as apoptosis. METHODS: Human bronchial cells (BEAS-2B) were treated with cigarette smoke extracts from traditional cigarettes (TC) and HNBC. Western blot was performed to assess protein citrullination and carbamylation, while apoptosis was assessed by flow cytometry, after staining with annexin V-FITC/PI and western blot through enzyme Parp1 evaluation. RESULTS: The exposure of BEAS-2B to HNBC or TC extracts causes significantly increased citrullination and carbamylation of proteins, compared with untreated cells. Furthermore, it leads to an augmentation of apoptosis, evaluated through annexin V-FITC/PI and enzyme Parp1 levels. CONCLUSION: Our results show that the extracts of HNBC and TC increase citrullination, carbamylation and influence cell death, causing an activation of apoptosis. This is the first study showing the effects of HNBC on PTMs and cell death mechanisms, raising alarm about the safety of these smoking alternatives in rheumatology. These data allow us to speculate that HNBC, like TC, could represent a risk factor for the development of RA in genetically susceptible individuals.
Ciancarella et al. (2026) studied this question.