No abstract

SUMMARYTo clarify the role of Th1-and Th2-type cytokines in the various outcomes of human alveolar echinococcosis (AE), the cytokine immune response of self-cured patients was studied and compared with those of progressive AE patients and healthy subjects. Self-cured patients were divided into two groups according to the following clinical features: subjects who had positive Echinococcus multilocularis serologies and hepatic calcifications typical of AE were classified as`abortive AE' patients, and those who had positive E. multilocularis serologies but no hepatic lesions or calcifications detectable by ultrasonography were classified as`positive serology' subjects. Secretions of IL-5, IL-10 and interferon-gamma, and expression of IL-5 mRNA were evaluated in peripheral blood mononuclear cells (PBMC) stimulated in vitro with the mitogen phytohaemagglutinin-C or specific E. multilocularis antigenic preparations. The cytokine profile of abortive AE patients was the opposite of that observed in progressive AE patients. An intermediate profile was observed in positive serology subjects. PBMC from abortive AE patients, whether non-stimulated or stimulated with PHA and antigenic preparations, secreted significantly lower levels of IL-10 than those isolated from progressive AE patients. Our observations seem to confirm the regulatory role of IL-10 in the immunopathology of human AE.

Evidence in animal intermediate hosts that susceptibility to larval infection with Echinococcus multilocularis is restricted to individual host factors prompted us to investigate the susceptibility markers in humans. Because antigens of the extracellular parasite E. multilocularis are possibly presented by MHC molecules in a restricted way, we speculated that MHC polymorphism may influence resistance of the host towards infection and course of disease. We studied HLA-A, -B, -DRB1, -DQB1 and -DPB1 polymorphism in 151 patients with alveolar echinococcosis. Patients with an observation period of more than 2 years were grouped according to the clinical follow-up into cured (no recurrence following surgery) patients and patients with regressive or progressive forms of disease during benzimidazole chemotherapy. By comparing phenotypic frequency between patients with alveolar echinococcosis and healthy controls, HLA-DRB1*11 was associated with a reduced risk for disease development (odds ratio=0.55, 95% confidence interval=0.34-0.88; P=0.01). HLA-DQB1*02 was more frequent in patients with progressive disease when compared with patients with regressive disease (54.3% vs 28.3%, P=0.02). The result suggests that HLA-DRB1*11 might confer protection against alveolar echinococcosis and that HLA-DQB1*02 may indicate a risk for progressive disease development. The findings may facilitate the search for immunodominant T-cell epitopes of E. multilocularis.

Between 1986 and 1991, 21 patients received liver grafts in our center for incurable alveolar echinococcosis (AE). The aim of this study was to analyze the long-term results in 15 of these 21 patients who survived more than 1 year after undergoing a liver transplantation (LT). The follow-up, mainly aimed at the diagnosis of recurrence, consisted of repeated radiological and specific immunological investigations. The role of pre- and post-LT benzimidazole (BZM) therapy was also evaluated. Among the 15 patients, 8 patients had a palliative LT related to previously known pulmonary AE metastases and/or inextirpable abdominal parasitic foci. In the 7 remaining patients, LT was considered curative. In June 1998, the mean follow-up duration was 96 months (range: 28-138 months). Five late deaths occurred, 2 of them were directly related to residual AE. A reinfection of the graft was observed in 4 patients. Preoperative BZM therapy seemed useful in preventing or delaying the parasitic recurrence. Post-LT BZM was able to stabilize and even to reduce residual AE. The anti-Em2 enzyme-linked immunosorbent assay (ELISA), which is the standard test used in patient follow-up after partial liver resection for AE, did not appear useful in detecting recurrence here; however, an ELISA, using a crude heterologous antigen (Echinococcus granulosus) allowed early diagnosis of residual AE. In conclusion, primary disease recurrence is not rare after LT for AE. Immunosuppressive therapy may favor larval growth in extrahepatic sites; therefore, an extensive extrahepatic radiological check-up has to be performed before LT. BZM therapy seems to stabilize residual foci. Anti-Eg immunoglobulin G (IgG) follow-up is the most useful test for early diagnosis of parasite recurrence.

SUMMARYDifferences have been shown between HLA characteristics of patients with different courses of alveolar echinococcosis (AE). Notably the HLA B8, DR3, DQ2 haplotype was associated with more severe forms of this granulomatous parasitic disease. We compared IL-10, IL-5, interferon-gamma (IFN-g) and tumour necrosis factor (TNF) secretion by peripheral blood mononuclear cells (PBMC) isolated from eight HLA-DR3 1 , DQ2 1 , B8 1 AE patients and from 10 HLA-DR3 2 , DQ2 2 , B8 2 patients after nonspecific mitogenic and specific Echinococcus multilocularis antigenic in vitro stimulation. PBMC from seven HLA-DR3 1 , DQ2 1 , B8 1 healthy subjects and nine HLA-DR3 2 , DQ2 2 , B8 2 subjects were also studied as controls. PBMC from AE patients with HLA DR3 1 , DQ2 1 haplotype secreted higher levels of IL-10 without any stimulation and after specific antigenic stimulation than did patients without this haplotype. Higher levels of IL-5 and IFN-g were also produced by these patients' PBMC after stimulation with non-purified parasitic antigenic preparations; however, the specific alkaline phosphatase antigen extracted from E. multilocularis induced only Th2-type cytokine secretion. A spontaneous secretion of TNF by HLA DR3 1 , DQ2 1 B8 1 AE patients was also found. These results suggest that HLA characteristics of the host can influence immune-mediated mechanisms, and thus the course of AE in humans; specific antigenic components of E. multilocularis could contribute to the preferential Th2-type cytokine production favoured by the genetic background of the host.