Cytokine genetic profile in Whipple’s disease

Biagi, Federico; Badulli, C.; Feurle, Gerhard E.; Müller, Christian; Moos, Verena; Schneider, Thomas; Marth, Thomas; Mytilineos, Joannis; Garlaschelli, F.; Marchese, A.; Trotta, Lucia; Bianchi, Paola Ilaria; M, Di Stefano; Cremaschi, A. L.; Silvestri, Annalisa De; Salvaneschi, L.; Martinetti, Miryam; Corazza, Gino Roberto

doi:10.1007/s10096-012-1677-8

Cited by 31 publications

(16 citation statements)

References 30 publications

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“…There is evidence for a genetic predisposition to T. whipplei infection. Genetic causes for the difference in susceptibility, recurrent infections, and some familial cases have been reported for T. whipplei (16,(66)(67)(68)(69)(70). Several immunerelated genes have been shown to correlate with disease susceptibility.…”

Section: Pathogenesis Predisposing Factors For Classic Whipple's Diseasementioning

confidence: 99%

“…The contribution of this immunological defect is probably specific, as patients with Whipple's disease do not seem to suffer more often from other infections than the general population (33,73). Human leukocyte alleles (HLA) (which are also important factors in the generation of immune responses) are other contributing risk factors, and in one study, 26 patients were positive for HLA DRB1*13 and/or DQB1*06 (16,62,69,70,74). The genetic cytokine profiles of 111 German patients and 22 Italian patients were analyzed, and these patients were all low secretors of transforming growth factor ␤1 (TGF-␤1) and high producers of IL-4 (70).…”

Section: Pathogenesis Predisposing Factors For Classic Whipple's Diseasementioning

confidence: 99%

“…IL-4 is known to downregulate IL-12 and gamma interferon (IFN-␥) secretion (61), while TGF-␤1 activates the Th17 subset (75). This immunological background may be responsible for the diminished Th1 and Th17 reactivity, which is suggested to contribute to the transition from the initial infection to classic Whipple's disease (70). There is also evidence for an association with IL-16 polymorphisms and some other Th2 response genes that probably contribute to long-term carriage of T. whipplei (69,70,76).…”

Section: Pathogenesis Predisposing Factors For Classic Whipple's Diseasementioning

confidence: 99%

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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%

Section: Pathogenesis Predisposing Factors For Classic Whipple's Diseasementioning

confidence: 99%

Section: Pathogenesis Predisposing Factors For Classic Whipple's Diseasementioning

confidence: 99%

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Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

et al. 2017

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“…Furthermore, no other immunological deficits were detected, thus leading to the hypothesis of a relationship between Whipple's disease and cellular immune dysfunction. According to the literature, patients with Whipple's disease have a markedly altered Th1 reactivity and their levels of interferon-γ are reduced [16,17]. Such alterations may be responsible for an increased susceptibility to some opportunistic infections such as esophageal candidiasis.…”

Section: Discussionmentioning

confidence: 95%

Whipple’s disease concomitant with candida esophagitis and subsequent Giardia lamblia coinfection

Sulis¹,

Villanacci²,

Missale³

et al. 2014

European Journal of Gastroenterology &Amp; Hepatology

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Whipple's disease is a rare systemic condition resulting from a chronic infection by Tropheryma whipplei. Clinical presentation can be widely heterogeneous, often leading to delayed diagnosis and treatment. Furthermore, little is known about the underlying pathogenic mechanisms, although several abnormalities in immune cell function have been observed. We describe the case of a 51-year-old woman presenting with dysphagia, odynophagia, long-lasting low-grade fever, and malabsorption syndrome who underwent an upper gastrointestinal endoscopy showing esophageal candidiasis. On the same occasion, duodenal biopsies were also performed, with evidence of mucosal infiltration of periodic acid-Schiff-positive and CD68+ foamy macrophages at microscopic examination. Such findings were suggestive of Whipple's disease, as also confirmed by molecular analysis by PCR for T. whipplei. No specific risk factors were identified in our patient that could explain the occurrence of an opportunistic infection such as candida esophagitis, thus leading to the hypothesis of a direct correlation with Whipple's disease. Interestingly, a Giardia lamblia coinfection was subsequently identified, which is consistent with an underlying immune deficit although still undefined.

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“…Since T. whipplei is common in the environment and genetically heterogeneous (7)(8)(9), the discrepancy among the widespread presence of T. whipplei, the frequency of self-limiting infections with T. whipplei (10), and the rarity of the disease is likely to be explained by immunogenetic host factors and susceptibility to the infection. It was recently shown that CWD is associated with the human leukocyte antigens DRB1*13 and DQB1*06 and that the cytokine genetic profile of CWD patients is skewed toward T-helper cell type 2 (Th2) and regulatory T-cell responses (11,12). Family cases of the disease have also been described (13)(14)(15).…”

Section: Lassical Whipple's Disease (Cwd) Is a Rare Chronic Systemimentioning

confidence: 99%

Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease

et al. 2017

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Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-␥) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei, the proportions of activated effector CD4 ϩ T cells, determined as CD40L ϩ IFN-␥ ϩ , were significantly lower in patients with CWD than in healthy controls; CD8 ϩ T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei-specific degranulation, although CD69 ϩ IFN-␥ ϩ CD8 ϩ T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei-derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei-derived proteins may contribute to the pathogenesis of CWD.

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Cytokine genetic profile in Whipple’s disease

Cited by 31 publications

References 30 publications

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Whipple’s disease concomitant with candida esophagitis and subsequent Giardia lamblia coinfection

Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease

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