Serological microarray for a paradoxical diagnostic of Whipple’s disease

• Published in: European journal of clinical microbiology & infectious diseases 2008-10, Vol.27 (10), p.959-968
• Main Authors: Bonhomme, C. J., Renesto, P., Nandi, S., Lynn, A. M., Raoult, D.
• Format: Article
• Language: English
• Subjects: Antibodies; Antibodies, Bacterial - blood; Antigens; Asymptomatic; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Candidates; Carrier State - diagnosis; Cloning; Disease; Gastroenterology. Liver. Pancreas. Abdomen; Genomes; Humans; Immune response; Immunization; Immunoglobulin A - blood; Immunoglobulin G - blood; Infections; Infectious diseases; Internal Medicine; Medical Microbiology; Medical sciences; Other diseases. Semiology; Penicillin; Proteins; Serologic Tests - methods; Serology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tropheryma - immunology; Tropheryma - isolation & purification; Whipple Disease - diagnosis
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-008-0528-0

Whipple’s disease is a systemic chronic infection caused by Tropheryma whipplei . Asymptomatic people may carry T. whipplei in their digestive tract and this can be determined by PCR, making serological diagnosis useful to distinguish between carriers and patients. Putative antigenic proteins were selected by computational analysis of the T. whipplei genome, immunoproteomics studies and from literature. After expression, putative T. whipplei antigens were screened by microimmunofluorescence with sera of immunized rabbit. Selected targets were screened by microarray using sera from patients and carriers. Paradoxically, with 19 tested recombinant proteins and a glycosylated native protein of T. whipplei , a higher immune response was observed with asymptomatic carriers. In contrast, quantification of human IgA exhibited a higher reaction in patients than in carriers against 10 antigens. These results were used to design a diagnostic test with a cut-off value for each antigen. A blind test assay was performed and was able to diagnose 6/8 patients and 11/12 carriers. Among people with positive T. whipplei PCR of the stool, patients differ from carriers by having positive IgA detection and a negative IgG detection. If confirmed, this serological test will distinguish between carriers and patients in people with positive PCR of the stool.