A Paradoxical Screening Serological Assay for the Diagnosis of Whipple’s Disease (infection with Tropheryma whipplei)

Abstract

ABSTRACTWhipple’s disease (WD) is a rare infection due to Tropheryma whipplei. Following in-vitro cultivation of T. whipplei, an indirect-immunofluorescence serological assay (IFA) was developed. We tested the hypothesis that this assay could be used to either identify WD patients, or rule out WD, in patients in whom the diagnosis is being considered, based on the antibody titers of their IgM and IgG antibody responses. In this small study fourteen WD patients and 22 healthy volunteers’ sera were obtained from across Australia. All specimens were coded and de-identified before testing. A patient with an IgG antibody titer of ≤1:16 may have WD [sensitivity 57% (8/14) and specificity close to 100% (22/22)]. High IgM antibody titers (≥1:256) were more common in WD patients [sensitivity 50% (7/14) and specificity 86% (19/22)] than in controls. The area under Receiver-Operator-Characteristic curve for IgG in the IFA assay was 0.84 (95% CI 0.69-1.00). At an IgG antibody titer of ≤1:16 the Youden’s index was 0.57. WD patients’ under-produce IgG antibody to T.whipplei but are more likely to over-produce IgM antibodies. This screening IFA serological assay may be clinically useful in detecting those with a possible diagnosis of WD. Patients with an IgG antibody titer of ≤1:16 and an IgM antibody titer of ≥1:256 may have WD and should proceed to a tissue biopsy and PCR for confirmation. Further validation of this assay, by increasing the sample size, by testing it in patients with non-WD disease and trialing in other countries should be undertaken.