Malondialdehyde–Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies

Background: Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUDs) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde–acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Methods: Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (−AUD/+smoke), AUD without smoke (+AUD/−smoke), and non-AUD/nonsmokers (−AUD/−smoke). Results: We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke versus −AUD/−smoke. No significant increase in MAA adducts was observed in −AUD/+smoke or in +AUD/−smoke compared to −AUD/−smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After 1 week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. Conclusions: MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.