Elevation of Serum B-Cell Activating Factor Levels During Visceral Leishmaniasis

Goto, Yasuyuki; Omachi, Satoko; Sanjoba, Chizu; Matsumoto, Yoshitsugu

doi:10.4269/ajtmh.14-0260

Cited by 19 publications

(16 citation statements)

References 17 publications

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“…3). The significance of BAFF in infected humans is not as clear as animal models suggest, because patients with visceral leishmaniasis also manifest elevated serum BAFF levels, but a correlation with serum IgG levels was not found (166). In the same study, a second group of patients with Chagas' disease did not have elevated serum BAFF or increased IgG levels.…”

Section: Parasites Leishmaniasis and Chagas' Diseasementioning

confidence: 89%

The Role of BAFF System Molecules in Host Response to Pathogens

Sakai

Akkoyunlu

2017

Clin Microbiol Rev

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The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.

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Section: Parasites Leishmaniasis and Chagas' Diseasementioning

confidence: 89%

The Role of BAFF System Molecules in Host Response to Pathogens

Sakai

Akkoyunlu

2017

Clin Microbiol Rev

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“…Therefore, it is possible that marked changes in cytokine/chemokine levels during malaria [51][52][53], as well as Plasmodium immune-modulatory molecules [38] drive BAFF/APRIL production by these cells. In the recent years, many research articles have reported a role for BAFF/APRIL system in the pathogenesis of autoimmune and infectious diseases [23,26,[31][32][33][34][35], including malaria [35,36,54]. However, while there is some evidence that BAFF plays a role in determining the outcome of P. falciparum malaria, nothing is known about the role of the follows: 1) APRIL in any malaria or 2) BAFF/APRIL system in P. vivax malaria.…”

Section: Malaria Is Characterized By Many Pathophysiological Changes mentioning

confidence: 99%

“…The APRIL and/or BAFF plasma levels are upregulated in many noninfectious [26,[68][69][70][71][72][73][74][75][76] and infectious diseases [32,73,77,78], including malaria [36,54] that are often accompanied by polyclonal B-cell activation, hypergammaglobulinemia, autoimmune disorders and lymphopenia. In malaria, polyclonal B-cell activation has been shown in the acute phase of P. vivax and P. falciparum malaria [15], which decreases 5-15 days after the beginning of treatment [15], with similar transient kinetics of IL-10, APRIL and/or BAFF levels, observed in our study.…”

Section: Malaria Is Characterized By Many Pathophysiological Changes mentioning

confidence: 99%

“…In the recent years, several studies have been shown that BAFF, APRIL, and their receptors play a significant role in the pathogenesis of various noninfectious and infectious diseases [23,26,[31][32][33][34][35], including BAFF in malaria [18,35,36]. In P. falciparum malaria, BAFF levels are increased in plasma samples from infected children in Kenya [36] and in placental tissue from infected pregnant women in Tanzania [37], which correlate with disease pathogenesis and severity.…”

Section: Introductionmentioning

confidence: 99%

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Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

Pinna

Santos

Perce-da-Silva

et al. 2018

Immunity Inflam & Disease

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IntroductionA proliferation‐inducing ligand (APRIL) and B cell activation factor (BAFF) are known to play a significant role in the pathogenesis of several diseases, including BAFF in malaria. The aim of this study was to investigate whether APRIL and BAFF plasma concentrations could be part of inflammatory responses associated with P. vivax and P. falciparum malaria in patients from the Brazilian Amazon.MethodsBlood samples were obtained from P. vivax and P. falciparum malaria patients (n = 52) resident in Porto Velho before and 15 days after the beginning of treatment and from uninfected individuals (n = 12). We investigated APRIL and BAFF circulating levels and their association with parasitaemia, WBC counts, and cytokine/chemokine plasma levels. The expression levels of transmembrane activator and calcium‐modulating cyclophilin ligand interactor (TACI) on PBMC from a subset of 5 P. vivax‐infected patients were analyzed by flow cytometry.ResultsAPRIL plasma levels were transiently increased during acute P. vivax and P. falciparum infections whereas BAFF levels were only increased during acute P. falciparum malaria. Although P. vivax and P. falciparum malaria patients have similar cytokine profiles during infection, in P. vivax acute phase malaria, APRIL but not BAFF levels correlated positively with IL‐1, IL‐2, IL‐4, IL‐6, and IL‐13 levels. We did not find any association between P. vivax parasitaemia and APRIL levels, while an inverse correlation was found between P. falciparum parasitaemia and APRIL levels. The percentage of TACI positive CD4+ and CD8+ T cells were increased in the acute phase P. vivax malaria.ConclusionThese findings suggest that the APRIL and BAFF inductions reflect different host strategies for controlling infection with each malaria species.

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“…This pathway strictly requires IFN‐I signaling , which seems to be necessary for enhancing antibody production. Elevated levels of B cell activating factor BAFF were also proposed as another possible mechanism . Interestingly, T follicular helper cells (TFh) do not seem to play a role in the induction or maintenance of hypergammaglobulinemia .…”

Section: Introductionmentioning

confidence: 99%

Hypergammaglobulinemia sustains the development of regulatory responses during chronic Leishmania donovani infection in mice

Silva‐Barrios

Stäger

2019

Eur J Immunol

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Visceral leishmaniasis, a chronic, potentially fatal disease, is characterized by high production of low-affinity antibodies. In humans, hypergammaglobulinemia is prediction of disease progression. Nevertheless, the contribution of hypermutated and/or classswitched immunoglobulins to disease pathogenesis has never been studied. Using Aicda −/− mice and the experimental model of Leishmania donovani infection, we demonstrate that the absence of hypermutated and/or class-switched antibodies was associated with increased resistance to disease, stronger protective Th1 responses, and a lower frequency of regulatory IFNγ + IL-10 + CD4 T cells. Interestingly, stronger Th1 responses and the absence of IFNγ + IL-10 + CD4 T cells during chronic infection in infected Aicda −/− mice were not caused by a T-cell intrinsic effect of AID, but by changes in the cytokine environment during chronic disease. Indeed TNF, IL-10 and IFN-ß expressions were only upregulated in the presence of hypermutated, class-switched antibodies and hypergammaglobulinemia at later stages of infection. Taken together, our results suggest that hypergammaglobulinemia sustains inhibitory responses during chronic visceral leishmaniasis.Keywords: AID r hypergammaglobulinemia r Leishmania donovani r regulatory T cells r T helper cells Additional supporting information may be found online in the Supporting Information section at the end of the article.

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Elevation of Serum B-Cell Activating Factor Levels During Visceral Leishmaniasis

Cited by 19 publications

References 17 publications

The Role of BAFF System Molecules in Host Response to Pathogens

The Role of BAFF System Molecules in Host Response to Pathogens

Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

Hypergammaglobulinemia sustains the development of regulatory responses during chronic Leishmania donovani infection in mice

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