An inverse association between plasma levels of α2-macroglobulin and α1- antitrypsin in COPD patients

Compared to normal PiMM, individuals with α1-antitrypsin (AAT) PiZZ (Glu342Lys) genotype are at higher risk of developing early-onset chronic obstructive pulmonary disease (COPD)/emphysema. We aimed to investigate putative differences in plasma levels of acute phase proteins (APP) and neutrophil transcriptomes between PiMM and PiZZ COPD patients. Nephelometric analysis of seven plasma APPs we performed in 67 PiMM and 44 PiZZ COPD patients (21 with and 19 without intravenous AAT therapy (IV-AAT)) in stable condition. For RNA sequencing, blood neutrophils were isolated from 6 PiMM and 10 PiZZ patients (4 with and 6 without IV-AAT). Western blotting using specific mouse monoclonal antibodies (2C1 and LG96) determined plasma levels of Z-AAT polymers. In addition to lower plasma AAT, PiZZ patients had higher α2-macroglobulin (A2MG) levels than PiMM patients. PiZZ patients who received IV-AAT had higher AAT but lower A2MG values than PiZZ without IV-AAT. Regardless of the AAT genotype, AAT levels inversely correlated with A2MG, and the AAT/A2MG ratio directly correlated with lung diffusion capacity (DCLO%). All PiZZ patients had circulating Z-AAT polymers, which correlated directly with A2MG and inversely with the FEV1/FVC ratio. Combined measurement of plasma AAT and A2MG levels may be of clinical value in assessing the progression of COPD and requires further attention. NSC2018/29/B/NZ5/02346