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

• Published in: Clinical and experimental immunology Vol. 121; no. 3; pp. 491 - 498
• Main Authors: Godot, V., Harraga, S., Beurton, I., Tiberghien, P., Sarciron, E., Gottstein, B., Vuitton, D. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2000; Blackwell; Blackwell Science Inc
• Subjects: alveolar echinococcosis; Animals; Antigens, Helminth - administration & dosage; Antigens, Helminth - isolation & purification; Biological and medical sciences; Case-Control Studies; cellular immunity; Cytokines - genetics; Cytokines - metabolism; Diseases caused by cestodes; Echinococcoses; Echinococcosis - etiology; Echinococcosis - genetics; Echinococcosis - immunology; Echinococcus - immunology; Echinococcus multilocularis; g-Interferon; Haplotypes; Helminthic diseases; histocompatibility locus HLA; HLA Antigens - genetics; HLA-B8 Antigen - genetics; HLA-DQ Antigens - genetics; HLA-DR3 Antigen - genetics; Humans; IL‐10; IL‐5; Immunity to Infection; In Vitro Techniques; Infectious diseases; Interferon-gamma - genetics; Interferon-gamma - metabolism; interferon‐gamma; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-5 - genetics; Interleukin-5 - metabolism; Leukocytes, Mononuclear - immunology; Medical sciences; Parasitic diseases; RNA, Messenger - genetics; RNA, Messenger - metabolism; Th2 Cells - immunology; Tumor Necrosis Factor-alpha - metabolism; tumour necrosis factor; Human; HLA-System; Immune response; Major histocompatibility system; Cytokine; Class II histocompatibility antigen; Plathelmintha; Hepatic disease; Cellular immunity; Parasitosis; Cestoda; Helminthiasis; Cestode disease; Infection; Echinococcus multilocularis; Interleukin 5; Risk factor; Interleukin 10; Helmintha; Digestive diseases; Invertebrata; Echinococciasis; Haplotype; Gamma interferon
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2000.01309.x

Differences 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‐γ) and tumour necrosis factor (TNF) secretion by peripheral blood mononuclear cells (PBMC) isolated from eight HLA‐DR3+, DQ2+, B8+ AE patients and from 10 HLA‐DR3−, DQ2−, B8− patients after non‐specific mitogenic and specific 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 with HLA DR3+, DQ2+ 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‐γ 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+, DQ2+ B8+ 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.