Researchers have developed a method of using quantitative inclusion analysis to quantify polymer aggregation in alpha-1 antitrypsin deficiency (AATD), which can be used to identify patients who are at risk of disease progression and suitable candidates for therapeutic intervention, according to a study published in PLoS One. 

The reason for studying polymer aggregation in AATD is that it is likely directly responsible for liver disease, such as cirrhosis. Hence, the retention of polymers in AATD can be described as toxic.

Current methods to characterize polymer aggregation in AATD are fairly limited — only a semiqualitative scale is available for use by pathologists. The researchers of this study decided to develop their own method to quantify polymer aggregation in AATD and understand how this causes pathology in patients. 

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Researchers enrolled patients with PiZZ AATD between November 2013 and October 2016 in a single-center prospective cohort study and examined their percutaneous liver biopsy samples. Exclusion criteria included a history of decompensated liver disease, as well as having undergone a previous lung or liver transplant. Researchers then used whole slides of liver biopsies to measure polymer-specific AAT using a novel polymer-specific monoclonal antibody. 

Researchers discovered that this method reliably quantified polymer accumulation in patients with AATD. The results showed that liver fibrosis was associated with polymer accumulation but not total AAT. They also found that men were more affected by AAT accumulation than women. 

The researchers acknowledged that advances in imaging and computer technology in recent years have made the gleaning of quantitative insights from tissue specimens possible.

Current therapy focuses on inhibiting AAT accumulation in the liver by means of autophagy or silencing of AAT expression before the patient develops advanced liver disease. The authors of the study wrote that the tools developed in this study “are intended to advance the quantitative value of histological samples for research” and “may also be useful for evaluating the efficacy of therapeutics aimed at reducing accumulation of AAT.” 


Marek G, Collinsworth A, Liu C, Brantly M, Clark V. Quantitative measurement of the histological features of alpha-1 antitrypsin deficiency-associated liver disease in biopsy specimens. PLoS One. Published online August 16, 2021. doi:10.1371/journal.pone.0256117