Decreased levels of interleukin-12p40 in the serum of patients with Whipple’s disease
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An impaired production of interleukin (IL)-12 and T cell interferon-γ (IFN-γ) of in vitro stimulated monocytes has been discussed as a pathogenic factor in Whipple’s disease (WD). It is unclear whether this defect of cellular immunity is translated to the humoral immune system and to serum correlates.
We analyzed the serum of 40 patients with Whipple’s disease in various degrees of disease activity by sandwich enzyme-linked immunosorbent assay for differences in cytokine and cell adhesion molecule concentrations compared with age- and sex-matched controls.
We observed a highly significant reduction of IL-12p40 levels (patients, 0.18±0.05 ng/ml (mean±SEM); controls, 3.19±0.39 ng/ml; p<0.01) in all stages of disease activity, whereas the concentration of IL-12p70 was comparable with controls. Furthermore, we observed a slight decrease in tumour necrosis factor α (TNF-α) concentrations in the serum of patients (patients, 6.36±0.90 pg/ml; controls, 10.5±1.23 pg/ml; p<0,05). The levels of other cytokines such as IFN-γ, IL-2, IL-13 and transforming growth factor β, as well as soluble cell adhesion molecules lymphocyte function-associated antigen 3 and intercellular adhesion molecule 1, were not significantly different compared with controls. Levels of immunoglobulin G2 (IgG2) measured in the serum of WD patients were below normal in 24 of 29 patients and were even below the 95% confidence interval in 10 patients.
Our data demonstrate a persistent defect of the cellular immune response with decreased serum concentrations of IL-12p40 and TNF-α and decreased IgG2 levels in a large group of WD patients. These data support as in vivo finding the results obtained in previous investigations with stimulated monocytes/lymphocytes. The isolated decrease in IL-12p40 may hint at possible defects in the IL-12/IFN-γ promoter system.
KeywordsWhipple’s disease Immunology Cytokines Immunoglobulin
analysis of variance
enzyme-linked immunosorbent assay
intercellular adhesion molecule
interferon consensus sequence binding protein
lymphocyte function-associated antigen
transforming growth factor beta
tumor necrosis factor alpha
We would like to acknowledge Prof. Dr. Feurle, Neuwied, Germany, for the provision of serum samples of some patients of group 1 (n=3), which have already been included in a therapy study, Studie zur Initialtherapie des Morbus Whipple (SIMW) of WD.
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