Circulating mannan-binding lectin, M-, L-, H-ficolin and collectin-liver-1 levels in patients with acute liver failure

Tea L Laursen, Thomas D Sandahl, Sidsel Støy, Frank V Schiødt, William M Lee, Hendrik Vilstrup, Steffen Thiel, Henning Grønbaek, US Acute Liver Failure Study Group, William M Lee, Julie Polson, Carla Pezzia, Ezmina Lalani, Linda S Hynan, Joan S Reisch, Anne M Larson, Jeffrey S Crippin, Laura Gerstle, Timothy J Davern, Katherine Partovi, Sukru Emre, Timothy M McCashland, Tamara Bernard, J Eileen Hay, Cindy Groettum, Natalie Murray, Sonnya Coultrup, A Obaid Shakil, Diane Morton, Andres T Blei, Jeanne Gottstein, Atif Zaman, Jonathan Schwartz, Ken Ingram, Steven Han, Val Peacock, Robert J Fontana, Suzanne Welch, Brendan McGuire, Linda Avant, Raymond Chung, Deborah Casson, Robert Brown Jr, Michael Schilsky, Laren Senkbeil, M Edwyn Harrison, Rebecca Rush, Adrian Reuben, Nancy Huntley, Santiago Munoz, Chandra Misra, Todd Stravitz, Jennifer Salvatori, Lorenzo Rossaro, Colette Prosser, Raj Satyanarayana, Wendy Taylor, Raj Reddy, Mical Campbell, Tarek Hassenein, Fatma Barakat, Alistair Smith, Tea L Laursen, Thomas D Sandahl, Sidsel Støy, Frank V Schiødt, William M Lee, Hendrik Vilstrup, Steffen Thiel, Henning Grønbaek, US Acute Liver Failure Study Group, William M Lee, Julie Polson, Carla Pezzia, Ezmina Lalani, Linda S Hynan, Joan S Reisch, Anne M Larson, Jeffrey S Crippin, Laura Gerstle, Timothy J Davern, Katherine Partovi, Sukru Emre, Timothy M McCashland, Tamara Bernard, J Eileen Hay, Cindy Groettum, Natalie Murray, Sonnya Coultrup, A Obaid Shakil, Diane Morton, Andres T Blei, Jeanne Gottstein, Atif Zaman, Jonathan Schwartz, Ken Ingram, Steven Han, Val Peacock, Robert J Fontana, Suzanne Welch, Brendan McGuire, Linda Avant, Raymond Chung, Deborah Casson, Robert Brown Jr, Michael Schilsky, Laren Senkbeil, M Edwyn Harrison, Rebecca Rush, Adrian Reuben, Nancy Huntley, Santiago Munoz, Chandra Misra, Todd Stravitz, Jennifer Salvatori, Lorenzo Rossaro, Colette Prosser, Raj Satyanarayana, Wendy Taylor, Raj Reddy, Mical Campbell, Tarek Hassenein, Fatma Barakat, Alistair Smith

Abstract

Background & aims: The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), M-, L-, and H-ficolin and collectin-liver-1 (CL-L1), which are predominantly synthesized in the liver. We aimed to study lectin levels in ALF patients and associations with clinical outcome.

Methods: Serum samples from 75 patients enrolled by the US ALF Study Group were collected on days 1 and 3. We included 75 healthy blood donors and 20 cirrhosis patients as controls. Analyses were performed using sandwich-type immunoassays (ELISA, TRIFMA).

Results: At day 1, the MBL level in ALF patients was 40% lower compared with healthy controls {[median (interquartile range) 0.72 μg/ml(0.91) vs. 1.15 (1.92)(P = 0.02]}, and increased significantly by day 3 [0.83 μg/ml(0.94)(P = 0.01)]. The M-ficolin level was 60% lower [0.54 μg/ml(0.50) vs. 1.48(1.01)(P < 0.0001)]. The CL-L1 level at day 1 was slightly higher compared with healthy controls [3.20 μg/ml(2.37) vs. 2.64(0.72)(P = 0.11)]; this was significant at day 3 [3.35(1.84)(P = 0.006)]. H- and L-ficolin levels were similar to healthy controls. Spontaneous ALF survivors had higher levels of MBL at day 1 [0.96 μg/ml(1.15) vs. 0.60(0.60)(P = 0.02)] and lower levels of L-ficolin by day 3 compared with patients who died or were transplanted [1.61 μg/ml(1.19) vs. 2.17(2.19)(P = 0.02)].

Conclusion: We observed significant dynamics in lectin levels in ALF patients, which may suggest they play a role in ALF pathogenesis. High MBL and low L-ficolin levels are associated with survival.

Keywords: acute liver failure; collectin-liver-1; complement system; ficolins; mannan-binding lectin; the lectin pathway.