Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia.
OBJECTIVE
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.
Kim
So Youn
SY
Section on Cellular Differentiation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-1830, USA.
Weinstein
David A
DA
Starost
Matthew F
MF
Mansfield
Brian C
BC
Chou
Janice Y
JY
D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002452:Cell Count; D054426:Chemokine CXCL2 / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D005953:Glycogen Storage Disease Type I / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*
D015415:Biomarkers; D054426:Chemokine CXCL2; D016209:Interleukin-8