Alfa-1-antitrypsin deficiency: a predisposing factor leading to invasive infections?

This case report highlights for the first time a possible link between the presence of alfa-1-antitrypsin deficiency (AATD) and the susceptibility to invasive infections. The current patient, with known AATD, initially presented with nausea, vomiting and headache secondary to Listeria monocytogenes rhombencephalitis. Further on, he developed respiratory insufficiency due to probable invasive pulmonary aspergillosis. Diagnostic work-up could not show any arguments for an underlying immunodeficiency or malignancy. The consecutive course of two rare invasive infections in a healthy individual posed the hypothesis if the underlying AATD could be considered a possible trigger for infections. Indirect clinical observations in literature indeed support this link and in addition, two possible pathophysiological pathways might explain the higher susceptibility for infections in AATD patients. First, alveolar macrophages are dysfunctional in AATD patients leading to a lower apoptotic clearance of bacteria and other (mostly intracellular) pathogens. Secondly, a lower release and lower function of tumour necrosis factor α (TNFα) is seen in alfa-1-antitrypsin depletion, priming the path to more frequent infections, a mechanism that is similar in anti-TNFα treated patients. This case is the first to report on severe or invasive infections related to AATD in humans.