Cytokine genetic profile in Whipple’s disease

• Published in: European journal of clinical microbiology & infectious diseases Vol. 31; no. 11; pp. 3145 - 3150
• Main Authors: Biagi, F., Badulli, C., Feurle, G. E., Müller, C., Moos, V., Schneider, T., Marth, T., Mytilineos, J., Garlaschelli, F., Marchese, A., Trotta, L., Bianchi, P. I., Di Stefano, M., Cremaschi, A. L., De Silvestri, A., Salvaneschi, L., Martinetti, M., Corazza, G. R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-11-2012; Springer; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cytokines; Cytokines - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Genotype & phenotype; Genotypes; Germany; Haplotypes; Heterogeneity; Humans; Immune response; Immunology; Infectious diseases; Internal Medicine; Italy; Male; Medical Microbiology; Medical sciences; Middle Aged; Nervous system; Other diseases. Semiology; Pathogens; Polymerase chain reaction; Polymorphism; Polymorphism, Genetic; Rare diseases; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Th2 Cells - immunology; Tropheryma - immunology; Tropheryma whipplei; Whipple Disease - genetics; Young Adult; Italy; Germany; Cytokine Gene; Italian Control; Human Leukocyte Antigen Allele; German Patient; Treg Cell; Infection; Microbiology; Intestinal malabsorption; Cytokine; Bacteriosis; Digestive diseases; Intestinal disease; Whipple disease; Genetic disease
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-012-1677-8

Whipple’s disease (WD) is a very rare chronic systemic condition characterised by a Th2/T regulatory (Treg) dysregulated immune response versus
Tropheryma whipplei
, a bacterium widely diffuse in the environment. To investigate whether this Th2/Treg polarised response has a genetic background, we investigated the Th1, Th2, Th17 and Treg cytokine genetic profile of 133 patients with WD. Thanks to the European Consortium on WD (QLG1-CT-2002-01049), the polymorphism of 13 cytokine genes was analysed in 111 German and 22 Italian patients using the polymerase chain reaction with sequence-specific primers (PCR-SSP) technique. The frequencies of the genotypes, haplotypes and functional phenotypes were compared with those obtained in 201 German and 140 Italian controls. Clinical heterogeneity was also considered. Functionally, WD patients may be considered as low producers of TGF-β1, having an increased frequency of the genotype
TGF-β1+869C/C,+915C/C
[12.3 % vs. 3.81 %, odds ratio (OR) = 4.131,
p
 = 0.0002] and high secretors of IL-4, carrying the genotype
IL-4-590T/T
(5.34 % vs. 1.17 %, OR = 5.09,
p
 = 0.0096). No significant association was found between cytokine polymorphism and clinical variability. Analogously to the recent cellular findings of a Th2/Treg polarised response, we showed that the cytokine genetic profile of WD patients is skewed toward a Th2 and Treg response. This was similar in both German and Italian populations. However, the significant deviations versus the controls are poorer than that expected on the basis of these recent cellular findings.