BACKGROUND/AIMS: Glycogen storage disease type Ia (GSD-Ia) patients manifest the long-term complication of hepatocellular adenoma (HCA) of unknown etiology. We showed previously that GSD-Ia mice exhibit neutrophilia and elevated serum cytokine levels. This study was conducted to evaluate whether human GSD-Ia patients exhibit analogous increases and whether in GSD-Ia mice a correlation exists between immune abnormalities and, biochemical and histological alterations in the liver. METHODS: Differential leukocyte counts and cytokine levels were investigated in GSD-Ia patients. Hepatic chemokine production, neutrophil infiltration, and histological abnormalities were investigated in GSD-Ia mice. RESULTS: We show that GSD-Ia patients exhibit increased peripheral neutrophil counts and serum interleukin-8 (IL-8). Compared to normal subjects, HCA-bearing GSD-Ia patients have a 2.8-fold higher serum IL-8 concentration, while GSD-Ia patients without HCA have a 1.4-fold higher concentration. Hepatic injury in GSD-Ia mice is evidenced by necrotic foci, markedly elevated infiltrating neutrophils, and increased hepatic production of chemokines. CONCLUSIONS: Peripheral neutrophilia and elevated serum chemokines are characteristic of GSD-Ia with HCA-bearing GSD-Ia patients having the highest serum IL-8. In GSD-Ia mice these elevations correlate with elevated hepatic chemokine levels, neutrophil infiltration, and necrosis. Taken together, peripheral neutrophilia and increased serum chemokines may indicate hepatic injuries in GSD-Ia.
BACKGROUND/AIMS: Glycogen storage disease type Ia (GSD-Ia) patients manifest the long-term complication of hepatocellular adenoma (HCA) of unknown etiology. We showed previously that GSD-Iamice exhibit neutrophilia and elevated serum cytokine levels. This study was conducted to evaluate whether humanGSD-Iapatients exhibit analogous increases and whether in GSD-Iamice a correlation exists between immune abnormalities and, biochemical and histological alterations in the liver. METHODS: Differential leukocyte counts and cytokine levels were investigated in GSD-Iapatients. Hepatic chemokine production, neutrophil infiltration, and histological abnormalities were investigated in GSD-Iamice. RESULTS: We show that GSD-Iapatients exhibit increased peripheral neutrophil counts and serum interleukin-8 (IL-8). Compared to normal subjects, HCA-bearing GSD-Iapatients have a 2.8-fold higher serum IL-8 concentration, while GSD-Iapatients without HCA have a 1.4-fold higher concentration. Hepatic injury in GSD-Iamice is evidenced by necrotic foci, markedly elevated infiltrating neutrophils, and increased hepatic production of chemokines. CONCLUSIONS: Peripheral neutrophilia and elevated serum chemokines are characteristic of GSD-Ia with HCA-bearing GSD-Iapatients having the highest serum IL-8. In GSD-Iamice these elevations correlate with elevated hepatic chemokine levels, neutrophil infiltration, and necrosis. Taken together, peripheral neutrophilia and increased serum chemokines may indicate hepatic injuries in GSD-Ia.
Authors: Li-Yuan Chen; Jeng-Jer Shieh; Baochuan Lin; Chi-Jiunn Pan; Ji-Liang Gao; Philip M Murphy; Thomas F Roe; Shimon Moses; Jerrold M Ward; Eric J Lee; Heiner Westphal; Brian C Mansfield; Janice Yang Chou Journal: Hum Mol Genet Date: 2003-08-12 Impact factor: 6.150
Authors: Young Mok Lee; Hyun Sik Jun; Chi-Jiunn Pan; Su Ru Lin; Lane H Wilson; Brian C Mansfield; Janice Y Chou Journal: Hepatology Date: 2012-08-27 Impact factor: 17.425
Authors: Wai Han Yiu; Young Mok Lee; Wen-Tao Peng; Chi-Jiunn Pan; Paul A Mead; Brian C Mansfield; Janice Y Chou Journal: Mol Ther Date: 2010-04-13 Impact factor: 11.454
Authors: Andrew Specht; Laurie Fiske; Kirsten Erger; Travis Cossette; John Verstegen; Martha Campbell-Thompson; Maggie B Struck; Young Mok Lee; Janice Y Chou; Barry J Byrne; Catherine E Correia; Cathryn S Mah; David A Weinstein; Thomas J Conlon Journal: J Biomed Biotechnol Date: 2011-01-03