Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

Tsubata, Shyunsuke; Ebe, Kazuto; Kawamura, Toshihiko; Ishimoto, Yuiko; Tomiyama-Miyaji, Chikako; Watanabe, Hirotaka; Sekikawa, Hiroho; Aoyagi, Yoshinobu; Abo, Toru

doi:10.1111/j.1440-1711.2005.01385.x

Cited by 8 publications

(11 citation statements)

References 15 publications

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“…Related to that, induction of antibodies against EPO molecule was observed in patients treated with recombinant human EPO which resulted in pure red cell aplasia [18]. Furthermore, the use of anti-EPO auto-antibodies as a therapy in murine malaria studies [19], is an indication of the important role it may play in severe malaria anaemia.…”

Section: Introductionmentioning

confidence: 99%

Anti-erythropoietin antibody levels and its association with anaemia in different strains of semi-immune mice infected with Plasmodium berghei ANKA

Helegbe

Huy

Yanagi

et al. 2013

Malar J

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BackgroundMalaria anaemia is still a major public health problem and its pathogenesis still unclear. Interestingly, the progression of anaemia is at relatively low parasitaemia with some mortality in the semi-immune individuals in the endemic areas despite adequate erythropoietin (EPO) synthesis. A recent study has shown that treatment with exogenous anti-erythropoietin (anti-EPO) antibodies (Ab) of infected mice gives protection against malaria infection, suggesting an important role for anti-EPO Ab in malaria. The objective of the study was to evaluate anti-EPO antibody levels in anaemic condition of different strains of semi-immune mice with malaria.MethodologySemi-immune status was attained in four mice strains (Balb/c, B6, CBA and NZW) by repeated infections with 104Plasmodium berghei ANKA, and treatment with chloroquine/pyrimethamine. ELISA was used to measure anti-EPO Ab, transferrin and EPO while inflammatory cytokines measurement was done using bead-based multiplex assay kit.ResultsThe mean anti-EPO Ab levels in the mice strains [Optical Density (OD) values at 450 nm: Balb/c (2.1); B6 (1.3); CBA (1.4) and NZW (1.7)] differed (p = 0.045), and were significantly higher when compared with uninfected controls, p < 0.0001, and mean anti-EPO Ab levels in the mice strains at recovery [OD values at 450 nm: Balb/c (1.8); B6 (1.1); CBA (1.5) and NZW (1.0) also differed (p = 0.0004). Interestingly, EPO levels were significantly high in NZW and low in Balb/c mice (p < 0.05), with those of B6 and CBA of intermediary values. Again, NZW were highly parasitaemic (20.7%) and the other strains (Balb/c, B6 and CBA) ranged between 2.2-2.8% (p = 0.015). Anti-EPO Ab correlated positively with extent of Hb loss (r = 0.5861; p = 0.003). Correlation of anti-EPO antibody with EPO was significant only in Balb/c mice (r = −0.83; p = 0.01). Significant levels of IL6 and IFNγ (p < 0.0001), both known to be associated with erythropoiesis suppression were observed in the Balb/c. Transferrin was significantly lower in Balb/c (p < 0.0001) when compared with the other mice strains (B6, CBA and NZW).ConclusionThis is the first ever report in estimating endogenous anti-EPO antibodies in malaria anaemia. The data presented here suggest that anti-EPO Ab is produced at infection and is associated with Hb loss. Host factors appear to influence anti-EPO antibody levels in the different strains of mice.

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Section: Introductionmentioning

confidence: 99%

Anti-erythropoietin antibody levels and its association with anaemia in different strains of semi-immune mice infected with Plasmodium berghei ANKA

Helegbe

Huy

Yanagi

et al. 2013

Malar J

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“…Within the first week after infection the size of the spleen increases severalfold, due in part to an influx of lymphocytes in both human (14,35,46) and mouse (54, 68) infections. Additionally, malaria-associated splenomegaly has been associated with increased erythropoiesis in mice (41,52,61,68). Malarial splenomegaly is accompanied by transient alterations in the microarchitecture during acute infection (2,9,29,32,54,65,67), which in mouse infections returns to normal several weeks after the acute parasitemia (1,54,67).…”

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confidence: 99%

Alterations of Splenic Architecture in Malaria Are Induced Independently of Toll-Like Receptors 2, 4, and 9 or MyD88 and May Affect Antibody Affinity

Cadman¹,

Abdallah²,

Voisine³

et al. 2008

Infect Immun

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Splenic microarchitecture is substantially altered during acute malaria infections, which may affect the development and regulation of immune responses. Here we investigated whether engagement of host Toll-like receptor 2 (TLR2), TLR4, TLR9, and the adaptor protein MyD88 is required for induction of the changes and whether antibody responses are modified when immunization takes place during the period of splenic disruption. The alterations in splenic microarchitecture were maximal shortly after the peak of parasitemia and were not dependent on engagement of TLR2, TLR4, or TLR9, and they were only minimally affected by the absence of the MyD88 adaptor molecule. Although germinal centers were formed in infected mice, they did not contain the usual light and dark zones. Immunization of mice with chicken gamma globulin 2 weeks prior to acute Plasmodium chabaudi infection did not affect the quantity or avidity of the immunoglobulin G antibody response to this antigen. However, immunization at the same time as the primary P. chabaudi infection resulted in a clear transient reduction in antibody avidity in the month following immunization. These data suggest that the alterations in splenic structure, particularly the germinal centers, may affect the quality of an antibody response during a malaria infection and could impact the development of immunity to malaria or to other infections or immunizations given during a malaria infection.

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“…Size of spleen increases several fold after infection, due to influx of lymphocytes in both human and mouse infection [12,13]. Malaria associated splenomegaly has been reported due to increased erythrocytes in mouse spleen [14,15]. Loss of marginal zone was observed with increase in parasitemia.…”

Section: Discussionmentioning

confidence: 99%

Structural Changes in Spleen Architecture upon Plasmodium berghei (NK-65) Infection in BALB/c Mice

Kumar¹,

Bagai²

2014

IOSRJPBS

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Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

Cited by 8 publications

References 15 publications

Anti-erythropoietin antibody levels and its association with anaemia in different strains of semi-immune mice infected with Plasmodium berghei ANKA

Anti-erythropoietin antibody levels and its association with anaemia in different strains of semi-immune mice infected with Plasmodium berghei ANKA

Alterations of Splenic Architecture in Malaria Are Induced Independently of Toll-Like Receptors 2, 4, and 9 or MyD88 and May Affect Antibody Affinity

Structural Changes in Spleen Architecture upon Plasmodium berghei (NK-65) Infection in BALB/c Mice

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