Strong transient expression of the type I interferon-induced MxA protein in hepatitis A but not in acute hepatitis B and C.
The human MxA protein is a new specific marker for type I interferon activity both in vitro and in vivo. In the study presented here, this interferon-induced marker, as well as the 2',5'-oligoadenylate synthetases, was measured in circulating mononuclear cells from 21 patients with acute hepatitis A, 20 patients with acute hepatitis B and 14 patients with acute hepatitis C for determination of the activation of the interferon system in these viral diseases. In acute hepatitis A a strong expression (10 of 10 patients) of the MxA protein and the 2',5'-oligoadenylate synthetase activity in peripheral-blood mononuclear cells was observed during the first 2 wk after onset of clinical symptoms. In this period the MxA protein concentrations reached levels similar to those measured in patients treated with up to 5 x 10(6) IU interferon-alpha three times a week. Beyond wk 3, in eight of eight patients with hepatitis A no increased MxA protein levels were found. In contrast, peripheral-blood mononuclear cells from patients with acute hepatitis B contained either no measurable MxA protein or only slightly higher levels of the MxA protein, as did those of most patients (12 of 14) with acute hepatitis C. The MxA protein levels of both hepatitis B and C patients were significantly lower (p < 0.05) than those found in hepatitis A patients. Furthermore, sera from 6 of 10 patients with hepatitis A, but none of 10 patients with acute hepatitis B and C, contained measurable MxA protein. This serum MxA protein may originate from interferon-exposed and subsequently damaged liver cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Jakschies
D
D
Department of Internal Medicine, Medical School Hanover, Germany.
Zachoval
R
R
Müller
R
R
Manns
M
M
Nolte
K U
KU
Hochkeppel
H K
HK
Horisberger
M A
MA
Deicher
H
H
Von Wussow
P
P
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000208:Acute Disease; D000998:Antiviral Agents / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D019204:GTP-Binding Proteins; D006506:Hepatitis A / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007943:Leukemia, Hairy Cell / Q000188:drug therapy / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D014176:Protein Biosynthesis; D011994:Recombinant Proteins
D000998:Antiviral Agents; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins