KF4 anti-CELA1 Antibody and Purified α1-Antitrypsin Have Similar but Not Additive Efficacy in Preventing Emphysema in Murine α1-Antitrypsin Deficiency.

Alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema. Chymotrypsin-like Elastase 1 (CELA1) is a serine protease neutralized by AAT and is important in emphysema progression. Cela1-deficiency is protective in a murine models of AAT-deficient emphysema. KF4 anti-CELA1 antibody prevented emphysema in PPE and cigarette smoke models in wild type mice. We evaluated potential toxicities of KF4 and its ability to prevent emphysema in AAT deficiency. We found Cela1 protein expression in mouse lung, pancreas, small intestine, and spleen. In toxicity studies, mice treated with KF4 25 mg/kg weekly for four weeks showed an elevation in blood urea nitrogen and slower weight gain compared to lower doses or equivalent dose IgG. In histologic grading of tissue injury of the lung, kidney, liver, and heart, there was some evidence of liver injury with KF4 25 mg/kg, but in all tissues, injury was less than in control mice subjected to cecal ligation and puncture. In efficacy studies, KF4 doses as low as 0.5 mg/kg reduced the lung elastase activity of AAT-/- mice treated with 0.2 units of PPE. In this injury model, AAT-/- mice treated with KF4 1 mg/kg weekly, human purified AAT 60 mg/kg weekly, and combined KF4 and AAT treatment had less emphysema than mice treated with IgG 1 mg/kg weekly. However, the efficacy of KF4, AAT, or KF4 & AAT was similar. While KF4 might be an alternative to AAT replacement, combined KF4 and AAT replacement does not confer additional benefit.

Participant diversity in ACER: 2010-2022.

BACKGROUND: Increasing diversity has become a priority for all fields working with human subjects due to historic exclusions and misrepresentations of participants with minoritized identities. To create a more representative and generalizable science of alcohol use, the Research Society on Alcohol (RSA) and its official journal, Alcohol: Clinical and Experimental Research (ACER), have increasingly incorporated diversity and inclusion into their posted values and programming. METHODS: We analyzed the content of articles published in ACER from 2010 through 2022 (6 years before and after the formation of RSA's Diversity Committee) to assess the reporting of participants' demographic information and whether there has been increased inclusion of diverse samples in alcohol research over time. Our team screened 3292 abstracts for data extraction; studies were included if they were primary analyses of data collected from human subjects (n = 1043). RESULTS: Reporting of all demographic variables increased over time, with significant increases in reporting for race/ethnicity, sexual orientation, gender identity, socioeconomic status (SES), income, and educational attainment. Demographic variables were also increasingly used in analyses. However, representation of research outside the United States diminished significantly over time. CONCLUSIONS: We provide recommended journal article reporting standards for ACER to continue the positive progress in reporting demographics in alcohol research and facilitate meta-analyses examining demographic modulation and the impact of social determinants of health.