<i>Tropheryma whipplei</i>Glycosylation in the Pathophysiologic Profile of Whipple’s Disease

C, Bonhomme; Renesto, Patricia; Desnues, Benoît; Ghigo, Éric; Lépidi, Hubert; Fourquet, Patrick; Fénollar, Florence; Henrissat, Bernard; Mège, Jean‐Louis; Raoult, Didier

doi:10.1086/597277

Cited by 35 publications

(30 citation statements)

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“…Paradoxically, the titer of specific immunoglobulin M (IgM) and IgG in classic Whipple's disease patients is very low or almost absent compared to carriers who do not show symptoms (87,88). This may be due to the bacterial antigen variation and/or masking from immunological detection, thereby allowing them to escape the humoral immune system (89). While IgM and IgG titers are low, the IgA titers in patients are usually much higher than in carriers (48).…”

Section: Pathogenesis Predisposing Factors For Classic Whipple's Diseasementioning

confidence: 99%

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

et al. 2017

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SUMMARY Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei, a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections.

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Section: Pathogenesis Predisposing Factors For Classic Whipple's Diseasementioning

confidence: 99%

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

et al. 2017

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“…During our preliminary study, analysis of the signal intensity of GpTw110 after deglycosylation demonstrated a large, significant decrease in sera from patients but not from carriers [14]. These data were then used to establish a diagnostic test.…”

Section: Western Blot Interpretationmentioning

confidence: 87%

“…Moreover, there was a paradoxical association of Whipple disease with a lower immunological response in patients, compared with asymptomatic carriers [13]. An antigenic shift in the bacteria, most likely linked to the glycosylation process, resulted in this loss of specificity [14]. An enzyme-linked immunosorbent assay that targeted part of the hsp65 gene was not accurate or reliable for distinguishing patients from control subjects [15].…”

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A ParadoxicalTropheryma whippleiWestern Blot Differentiates Patients with Whipple Disease from Asymptomatic Carriers

2009

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“…Thus, secretory immunity may be also impaired, since Th1 cells play a crucial role in mucosal B-cell differentiation (9). In addition, T. whipplei acquires a glycoproteic biofilm that might inhibit the specific humoral immune response (1). Indeed, in serum samples of Whipple's disease patients, reduced total IgG2 (11) and T. whipplei-specific IgG and IgM have been detected, whereas T. whipplei-specific IgA is enhanced compared to healthy persons (2).…”

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Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease

et al. 2010

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Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response toward T. whipplei. This T. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolish T. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection.Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei (15, 18). The major clinical manifestations of Whipple's disease are arthritis, weight loss, and diarrhea that resolve upon antimicrobial treatment (15).Immunoglobulins, especially IgA, are a major defense mechanism against infections at mucosal surfaces. IgA is secreted into the gut lumen, where it binds infectious agents, thereby blocking their adhesion and entry into the mucosa (9). Moreover, IgA is able to eliminate pathogens from the lamina propria and even binds viral proteins before assembly in the epithelial cells (8).The local immunological defects underlying the pathogenesis of Whipple's disease are poorly understood, and data on mucosal humoral immunity are lacking. We have shown that in the duodenum of Whipple's disease patients the numbers of T cells and unspecific and T. whipplei-specific Th1 reactivity are reduced compared to healthy controls, and that macrophages are alternatively activated (3,10,13,14). Thus, secretory immunity may be also impaired, since Th1 cells play a crucial role in mucosal B-cell differentiation (9). In addition, T. whipplei acquires a glycoproteic biofilm that might inhibit the specific humoral immune response (1). Indeed, in serum samples of Whipple's disease patients, reduced total IgG2 (11) and T. whipplei-specific IgG and IgM have been detected, whereas T. whipplei-specific IgA is enhanced compared to healthy persons (2).However, nothing is known about the quantitative production of immunoglobulins and the specificity of secretory IgA in the duodenal mucosa of Whipple's disease patients, the site of major replication of the pathogen. Thus, we quantified systemic and duodenal production of immunoglobulins and determined T. whipplei-specific secretory IgA in the supernatants of short-term cultured duodenal biopsy specimens to...

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Tropheryma whippleiGlycosylation in the Pathophysiologic Profile of Whipple’s Disease

Abstract: T. whipplei glycosylation is likely to impair antibody-mediated immune recognition in patients. Such an intracellular antigen masking system in bacteria has not previously been described.

Cited by 35 publications

References 35 publications

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

A ParadoxicalTropheryma whippleiWestern Blot Differentiates Patients with Whipple Disease from Asymptomatic Carriers

Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease

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