Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. II. Influence of the HLA B8, DR3, DQ2 haplotype

Differences have been shown between HLA characteristics of patients with di fferent courses of alveolar echinococcosis (AE). Notably the HLA B8, DR3, D Q2 haplotype was associated with more severe forms of this granulomatous pa rasitic disease. We compared IL-10, IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) secretion by peripheral blood mononuclear cell s (PBMC) isolated from eight HLA-DR3(+), DQ2(+), B8(+) AE patients and from 10 HLA-DR3(-), DQ2(-), B8(-) patients after non-specific mitogenic and spe cific Echinococcus multilocularis antigenic in vitro stimulation. PBMC from seven HLA-DR3(+), DQ2(+), B8(+) healthy subjects and nine HLA-DR3(-), DQ2( -), B8(-) subjects were also studied as controls. PBMC from AE patients wit h HLA DR3(+), DQ2(+) haplotype secreted higher levels of IL-10 without any stimulation and after specific antigenic stimulation than did patients with out this haplotype. Higher levels of IL-5 and IFN-gamma were also produced by these patients' PBMC after stimulation with non-purified parasitic antig enic preparations; however, the specific alkaline phosphatase antigen extra cted from E. multilocularis induced only Th2-type cytokine secretion. A spo ntaneous secretion of TNF by HLA DR3(+), DQ2(+) B8(+) AE patients was also found. These results suggest that HLA characteristics of the host can influ ence immune-mediated mechanisms, and thus the course of AE in humans; speci fic antigenic components of E. multilocularis could contribute to the prefe rential Th2-type cytokine production favoured by the genetic background of the host.