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Keywords:

  • cytokines;
  • IL-2;
  • IL-4;
  • IFN-γ;
  • IL-10;
  • lymphoproliferative responses;
  • Th1;
  • Th2

Abstract

Background:  Infection with hepatitis E virus (HEV) is a major cause of acute viral hepatitis in several developing countries. Although usually self-limiting and benign, the disease is particularly severe among pregnant women, with mortality rates reaching 15–20%.

Methods:  Immune parameters among pregnant women with acute hepatitis E (P-HEV) were investigated and compared with those in non-pregnant patients with hepatitis E (N-HEV), and healthy pregnant (PC) and non-pregnant (NPC) women.

Results:  Peripheral blood mononuclear cells (PBMC) from P-HEV patients had lower lymphocyte proliferation response to phytohemagglutinin (PHA) than those in the PC and NPC groups. A positive lymphocyte proliferation response to HEV antigen (HEVAg), a mixture of eight peptides derived from HEV proteins, was observed in 7/19 (37%) P-HEV patients, 3/9 (33%) N-HEV patients and only 2/21 (10%) PC and 2/14 (14%) NPC subjects; the stimulation indices in the P-HEV group were similar to the N-HEV group and higher than the PC group. Measurement of cytokine production by PBMC in response to PHA and HEVAg showed a reduction in production of T-helper 1 (Th1) cytokines and an increase in that of Th2 cytokines in the P-HEV group. Cytokine mRNA levels showed similar changes.

Conclusion:  These results show the existence of a Th2 bias in pregnant women with acute hepatitis E. The role of this Th2 bias in the greater severity of hepatitis E among pregnant women needs further investigation.