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
- 1.Whipple GH (1907) A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Bull Johns Hopkins Hosp 18:382–391Google Scholar
- 3.Dobbins WO III (1987) Whipple’s disease. Charles C. Thomas, Springfield, ILGoogle Scholar
- 4.Marth T (1996) Whipple-Erkrankung. In: Hahn EG, Riemann JF (eds) Klinische Gastroenterologie, 3rd edn. Thieme, Stuttgart, pp 947–951Google Scholar
- 12.Wilson KH, Blitchington R, Frothingham R, Wilson JAP (1991) Phylogeny of the Whipple’s disease-associated bacterium. Lancet II:474Google Scholar
- 19.Feurle GE, Dörken B, Schöpf E, Lenhard V (1979) HLA-B27 and defects in the T cell system in Whipple’s disease. Eur J Clin Investig 9:385Google Scholar
- 20.Feurle GE (1985) Association of Whipple’s disease with HLA-B27. Lancet 8:1336Google Scholar
- 21.Paulley JW (1952) A case of Whipple’s disease (intestinal lipodystrophy). Gastroenterol 22:128Google Scholar
- 29.Janeway CA, Travers P, Walport M, Shlomchik M (2001) Immunobiology: the immune system in health and disease, 5th edn. Garland, LondonGoogle Scholar
- 37.Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, Drysdale P, Jouanguy E, Doffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL (1998) Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280:1432–1435PubMedGoogle Scholar
- 38.Picard C, Fieschi C, Altare F, Al-Jumaah S, Al-Hajjar S, Feinberg J, Dupuis S, Soudais C, Al-Mohsen IZ, Genin E, Lammas D, Kumararatne DS, Leclerc T, Rafii A, Frayha H, Murugasu B, Wah LB, Sinniah R, Loubser M, Okamoto E, Al-Ghonaium A, Tufenkeji H, Abel L, Casanova JL (2002) Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am J Hum Genet 70:336–348PubMedGoogle Scholar