Alpha-1-antitrypsin (AAT) anomalies are associated with lung disease due to rapidly growing mycobacteria and AAT inhibits Mycobacterium abscessus infection of macrophages, Scandinavian Journal of Infectious Diseases, Informa Healthcare

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Alpha-1-antitrypsin (AAT) anomalies are associated with lung disease due to rapidly growing mycobacteria and AAT inhibits Mycobacterium abscessus infection of macrophages

2007, Vol. 39, No. 8 , Pages 690-696 (doi:10.1080/00365540701225744)

Edward D. Chan¹,²³,⁵, Aleksandra M. Kaminska¹, Wendy Gill¹, Kathryn Chmura¹,⁶, Nicole E. Feldman¹, Xiyuan Bai¹, Corinne M. Floyd¹, Kayte E. Fulton¹, Gwen A. Huitt¹,⁴, Matthew J. Strand⁷, Michael D. Iseman¹,³⁴ and Leland Shapiro⁴,⁵ ^†

¹From the Department of Medicine, National Jewish Medical and Research Center (NJMRC), Denver, CO, USA

²Program in Cell Biology, NJMRC, Denver, CO, USA

³Division of Pulmonary Sciences and Critical Care Medicine, NJMRC, Denver, CO, USA

⁴Division of Infectious Diseases, University of Colorado at Denver and Health Sciences Center, Denver, CO, USA

⁵Denver Veterans Affairs Medical Center, Denver, CO, USA

⁶University of Colorado School of Medicine, , USA

⁷Division of Biostatistics, NJMRC, , USA

^†Correspondence: Leland Shapiro, University of Colorado at Denver and Health Sciences Center, Department of Medicine, Division of Infectious Diseases, 4200 East 9th Avenue, Box B168, Denver, CO, 80262, USA, +303 399 8020, extn 3506, +303 393 4692 leland.shapiro@uchsc.edu

Rapidly growing mycobacteria (RGM) are ubiquitous in the environment but cause lung disease in only a fraction of exposed individuals. This variable susceptibility to disease implies vulnerability to RGM infection due to weakness in host defense. Since most persons who contract RGM lung disease have no known host defense defect, it is likely that uncharacterized host deficiencies exist that predispose to RGM infection. Alpha-1-antitrypsin (AAT) is a host factor that may protect individuals from respiratory infections. Therefore, we assessed AAT protein anomalies as a risk factor for RGM lung disease. In a cohort of 100 patients with RGM lung disease, Mycobacterium (M.) abscessus was the most prevalent organism, isolated in 64 (64%) subjects. Anomalous AAT proteins were present in 27% of the cohort, which is 1.6 times the estimated prevalence of anomalous AAT proteins in the United States population (p =0.008). In in vitro studies, both AAT and a synthetic inhibitor of serine proteases suppressed M. abscessus infection of monocyte-derived macrophages by up to 65% (p<0.01). AAT may be an anti-RGM host-defense factor, and anomalous AAT phenotypes or AAT deficiency may constitute risk factors for pulmonary disease due to RGM.