Elevated soluble HLA II protein levels in patients with alpha-1 antitrypsin deficiency with or without COPD

Elevated levels of human leukocyte antigen (HLA) proteins have been reported in several pathologic conditions that are associated with increased concentrations of white blood cells (e.g., infection, inflammation, and lymphoproliferative disorders). The mechanisms by which HLA proteins are solubilized from cell membranes are insufficiently understood. We hypothesized that HLA proteins may be cleaved from cell membranes by insufficiently inhibited leukocytic elastase, as expected in alpha-1 antitrypsin deficiency (A1ATD), resulting in elevated plasma levels of soluble HLA (sHLA) proteins. Using an enzyme-linked immunosorbent assay, we measured sHLA II levels in the peripheral blood of patients with A1ATD with or without co-existing chronic obstructive pulmonary disease (COPD), with COPD only, and in a control group. Mean (±SD) sHLA II plasma levels were 110 ± 200 pg/mL in patients with A1ATD and COPD (Group 1), 10 ± 30 pg/mL in patients with COPD without A1ATD (Group 2), 70 ± 90 pg/mL in patients with A1ATD without COPD (Group 3), and 10 ± 30 pg/mL in healthy donors (Group 4). Soluble HLA II plasma levels were significantly higher in Group 1 (P = .001) and Group 3 (P = .002) versus Group 4. Our preliminary results suggest that leukocytic elastase and probably other proteinases solubilize HLA proteins from cell membranes. This mechanism would operate in inflammation with elevated leukocytic elastase levels but more so with inflammation and A1ATD, where elastase would be insufficiently inhibited. If this mechanism is verified, plasma sHLA levels could potentially be used to measure cell damage due to proteinases and, therefore, for monitoring the therapeutic efficacy of alpha-1 antitrypsin (A1AT) augmentation therapy.