No evidence for association of the CD40, CD40L and BLYS polymorphisms, B-cell co-stimulatory molecules, with Brazilian endemic Plasmodium vivax malaria

Capobianco, Marcela Petrolini; Cassiano, Gustavo Capatti; Furini, Adriana Antônia Cruz; Storti-Melo, Luciane Moreno; Pavarino, Érika Cristina; Galbiatti, Ana Lívia Silva; Fraga, Valéria Daltibari; Conceição, Luciana Moran; Couto, Vanja Suely Calvosa D’Almeida; Couto, Alvaro A.R.A; Machado, Ricardo Luiz Dantas

doi:10.1093/trstmh/trt031

Cited by 7 publications

(7 citation statements)

References 24 publications

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“…These results are consistent with the findings of previous studies (45)(46)(47)(48). Additionally, the difference in comparison of the above indexes between the BLyS and the TLR-9 inhibition groups were not statistically significant, with the exception of TLR-9 mRNA and BLyS.…”

Section: Tlr-9 Mrna Expression Level --------------------------------supporting

confidence: 92%

Toll-like receptor-9 is involved in the development of B cell stimulating factor-induced systemic lupus erythematosus

et al. 2017

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Abstract. The objective of the present study was to investigate the role of Toll-like receptor (TLR)-9 in B lymphocyte stimulating factor (BLyS)-induced systemic lupus erythematosus (SLE) in mice. The anti-double stranded (ds)DNA antibody titer, levels of complement proteins (C3 and C4), interleukin (IL)-10 and the disease activity [assessed by the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level] were measured. A total of 21 transgenic female mice (aged 8-10 weeks and weighing 30-40 g) expressing the Epstein-Barr virus membrane antigen, BLLF1, were studied. Mice were randomly divided into the control, the BLyS inhibition and the TLR-9 inhibition groups, with 7 mice in each group. Mice in the blank control group received intraperitoneal injections of normal saline, mice in the BLyS inhibition group received intraperitoneal injections of anti-BR3 monoclonal antibody (5,000 ng/day) and mice in the TLR-9 inhibition group received intraperitoneal injections of anti-human TLR-9 antibody (250 ng/day). The treatment regimens continued for 10 days, followed by the collection of peripheral venous blood. The relative levels of TLR-9 mRNA were measured by reverse transcription-quantitative polymerase chain reaction. Furthermore, the BLyS protein concentration and IL-10 levels were measured by ELISA. TLR-9 mRNA, BLyS, IL-10, anti-dsDNA antibody titer, C3, C4, ESR and CRP levels of the blank control group were significantly higher than those of the other two groups (P<0.05). The differences in comparison of these indexes between the BLyS inhibition and TLR-9 inhibition groups were not statistically significant (P>0.05), with the exception of TLR-9 mRNA and BLyS. In conclusion, the TLR-9 signaling pathway may be important for BLyS-induced SLE, and regulation of the inflammatory immune level.

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Section: Tlr-9 Mrna Expression Level --------------------------------supporting

confidence: 92%

Toll-like receptor-9 is involved in the development of B cell stimulating factor-induced systemic lupus erythematosus

et al. 2017

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Section: Discussionmentioning

confidence: 99%

“…Thus, the discrepancies between APRIL and BAFF levels and/or correlations found in this study could also be associated with the different biological functions of APRIL and BAFF during malaria. In addition, we cannot rule out the possibility that genetic polymorphism in the human genes encoding APRIL and BAFF molecules and/or receptors [63][64][65], can also play a role in the aforementioned discrepancies. Consistent with our previous findings [51], the levels of all cytokines increased in the acute phase of both malaria infections and continued to increase after treatment, except for IL-10.…”

Section: Malaria Is Characterized By Many Pathophysiological Changes mentioning

confidence: 99%

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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“…However, it is noteworthy that the frequency of the T allele is significantly lower in African populations than in European populations [ 47 ], and this frequency may suggest a selective advantage of the C allele due to pressure exerted by malaria. However, in a case-control study conducted in the city of Macapá in the Brazilian Amazon, no association was found between polymorphism in the CD40 gene and susceptibility to vivax malaria [ 48 ]. This same study evaluated the influence of BLYS , CD40 , and CD40L polymorphisms on the antibody response against recombinant proteins of P .…”

Section: Discussionmentioning

confidence: 99%

“…However, it is of note that this subgroup consisted of approximately 50 individuals. Moreover, it remains possible that the conditions of malaria transmission and the genetic background of the populations differ between the municipalities of Macapá and Goianésia do Pará, which could explain the differences observed [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood–Stage Proteins of Plasmodium vivax

et al. 2016

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The development of an effective immune response can help decrease mortality from malaria and its clinical symptoms. However, this mechanism is complex and has significant inter-individual variation, most likely owing to the genetic contribution of the human host. Therefore, this study aimed to investigate the influence of polymorphisms in genes involved in the costimulation of B-lymphocytes in the naturally acquired humoral immune response against proteins of the asexual stage of Plasmodium vivax. A total of 319 individuals living in an area of malaria transmission in the Brazilian Amazon were genotyped for four SNPs in the genes CD40, CD40L, BLYS and CD86. In addition, IgG antibodies against P. vivax apical membrane antigen 1 (PvAMA–1), Duffy binding protein (PvDBP) and merozoite surface protein 1 (PvMSP–119) were detected by ELISA. The SNP BLYS –871C>T was associated with the frequency of IgG responders to PvAMA–1 and PvMSP–119. The SNP CD40 –1C>T was associated with the IgG response against PvDBP, whereas IgG antibody titers against PvMSP–119 were influenced by the polymorphism CD86 +1057G>A. These data may help to elucidate the immunological aspects of vivax malaria and consequently assist in the design of malaria vaccines.

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No evidence for association of the CD40, CD40L and BLYS polymorphisms, B-cell co-stimulatory molecules, with Brazilian endemic Plasmodium vivax malaria

Cited by 7 publications

References 24 publications

Toll-like receptor-9 is involved in the development of B cell stimulating factor-induced systemic lupus erythematosus

Toll-like receptor-9 is involved in the development of B cell stimulating factor-induced systemic lupus erythematosus

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

Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood–Stage Proteins of Plasmodium vivax

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