Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related anemia

Tsiakalos, Aristotelis; Kordossis, T.; Ziakas, Panayiotis D.; Kontos, Athanasios; Kyriaki, Despina; Sipsas, Nikolaos V.

doi:10.1016/j.jinf.2009.12.013

Cited by 12 publications

(14 citation statements)

References 27 publications

(28 reference statements)

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“…Alternatively, anaemia of chronic disease – in this case due to advanced HIV disease and related co-morbidities - has also been known to present a similar morphological picture. Another well studied cause of anemia in adults is the presence of antibodies to endogenous erythropoietin [21]. This in children has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Anaemia in HIV-infected children: severity, types and effect on response to HAART

2012

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BackgroundHIV and anaemia are major health challenges in Africa. Anaemia in HIV-infected individuals is associated with more rapid disease progression and a poorer prognosis if not addressed appropriately. This study aimed at determining the severity and types of anaemia among HIV infected children and its effect on short term response to antiretroviral therapy (ART).MethodsAt baseline, clinical and haematological parameters of 257 HIV-infected ART-naïve children aged 3 months to 18 years were assessed to determine the prevalence, severity and types of anaemia. ART eligible patients were started on therapy according to WHO criteria, enrolled (n=88) into an observational cohort and followed up for 6 months.ResultsAnaemia was present in 148/257 (57.6%) of children, including (93/148) 62.2% with mild anaemia, 47/148 (32.0%) moderate anaemia, and 7/148 (4.8%) with severe anaemia. The mean haemoglobin (hb) was lower among children with more advanced HIV disease (p<0.0001). Microcytic-hypochromic anaemia (44.9%) was the commonest type of anaemia. Anaemia was independently associated with young age (p <0.0001), advanced HIV WHO disease stage (p = 0.034) and low CD4 percentage (p = 0.048). The proportion of children who had attained viral suppression (viral load <400 copies/ml) at 3 months was significantly lower among the anaemic children, 31/58 (53.4%) compared to the non-anaemic children 26/30 (86.7%) (p=0.002). However, the difference in clinical and immunological response between the anaemic and non-anaemic patients did not reach statistical significance.ConclusionAnaemia is highly prevalent among HIV-infected children in a rural Ugandan clinic and is associated with poorer virological suppression. However, the anaemia did not impact clinical and immunological response to ART among these children.

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Section: Discussionmentioning

confidence: 99%

Anaemia in HIV-infected children: severity, types and effect on response to HAART

2012

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“…Studies in some auto-immune diseases and HIV patients revealed high level of anti-EPO auto-antibodies and its association with anaemia [8-10]. But this has not been studied in malaria anaemia cases.…”

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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“…It is important to point out that the erythropoietin ELISA originally used to detect anti-EPO autoantibodies in SLE [ 26 ] and then in HIV patients [ 11 , 12 ] has not been rigorously validated and is known to be prone to high rates of false positive results [ 27 , 28 ]. In the three studies reporting anti-EPO autoantibodies in HIV associated with anemia, well-characterized anti-EPO antibody samples from patients with pure red cell aplasia were not used for validation, but rather SLE and HIV patient sera was employed [ 11 – 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…These autoantibodies include those targeted against HLA-DR [ 7 ], interferon-α (IFN-α) [ 8 ], interleukin-2 (IL-2) [ 9 ], immunoglobulins [ 10 ] and EPO [ 11 – 13 ]. The presence of these antibodies has been inferred to cause immune suppression and anemia [ 7 – 9 , 11 , 12 , 14 , 15 ] In particular, anti-EPO autoantibodies have been found in 20% to 41% of untreated HIV patients and are associated with impaired erythropoiesis and HIV-associated anemia [ 11 – 13 ]. Despite these and other studies, the seroprevalence of autoantibodies against such cellular targets in HIV disease has not been substantiated employing defined recombinant proteins with new antibody profiling technologies.…”

Section: Introductionmentioning

confidence: 99%

Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects

et al. 2015

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Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO), interferon-α (IFN-α), interleukin-2 (IL-2), and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase Immunoprecipitation System (LIPS) was used to investigate the presence of such autoantibodies in HIV-infected adults. High levels of antibodies to HIV proteins such as capsid (p24), matrix (p17), envelope (gp41), and reverse transcriptase (RT) were detected using LIPS in both untreated and anti-retroviral-treated HIV-infected individuals but not in uninfected controls. LIPS readily detected anti-EPO autoantibodies in serum samples from subjects with presumptive pure red cell aplasia but not in any of the samples from HIV-infected or uninfected individuals. Similarly, subjects with HIV lacked autoantibodies to IFN-α, IL-2, HLA-DR and the immunoglobulin lambda light chain; all purported targets of molecular mimicry. While molecular mimicry between pathogen proteins and self-proteins is a commonly proposed mechanism for autoantibody production, the findings presented here indicate such a process is not common in HIV disease.

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Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related anemia

Cited by 12 publications

References 27 publications

Anaemia in HIV-infected children: severity, types and effect on response to HAART

Anaemia in HIV-infected children: severity, types and effect on response to HAART

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

Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects

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