Fine Epitope Specificity of Anti-erythropoietin Antibodies Reveals Molecular Mimicry With HIV-1 p17 Protein: A Pathogenetic Mechanism for HIV-1–Related Anemia

Tsiakalos, Aristotelis; Routsias, John G.; Kordossis, T.; Moutsopoulos, Haralampos Μ.; Tzioufas, Athanasios G.; Sipsas, Nikolaos V.

doi:10.1093/infdis/jir433

Cited by 35 publications

(28 citation statements)

References 28 publications

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“…The molecular mimicry between HIV protein and self-antigen may explain these higher risks of incident SLE and autoimmune haemolytic anaemia in patients with HIV. The molecular mimicry between HIV viral protein and self-antigens could induce autoantibody production2 19 and might be associated with the development of autoimmune diseases 28…”

Section: Discussionmentioning

confidence: 99%

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Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000–2012

Yen

Chuang

Jen³

et al. 2016

Ann Rheum Dis

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Section: Discussionmentioning

confidence: 99%

“…When HIV infects a host, it may induce production of autoantibodies due to the structural antigen similarity between viral proteins and self-antigens 2 3. The molecular mimicry between HIV protein and self-antigens could cause antibody cross-reactions and lead to development of autoimmune disease 4.…”

Section: Introductionmentioning

confidence: 99%

Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000–2012

Yen

Chuang

Jen³

et al. 2016

Ann Rheum Dis

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“…A recent report demonstrates that molecular mimicry between erythropoietin (EPO) and the HIV-1 p17 protein can lead to circulating auto-antibodies against endogenous EPO in some HIV ϩ patients, blunting the normal physiologic cytokine response to anemia. 18 Several studies have also demonstrated a direct effect of HIV on hematopoietic progenitor cells and EPO responsiveness. HIV-2 infection of BM progenitor cells in the in vitro setting has been shown previously to inhibit erythyropoiesis directly at the BFU-E and CFU-E stage of differentiation.…”

Section: Multifactorial Pathogenesis Of Anemia In Hivmentioning

confidence: 99%

Pathogenesis and clinical implications of HIV-related anemia in 2013

Redig¹,

2013

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Anemia is a common feature of HIV-related disease and has been uniformly demonstrated to be an independent predictor of morbidity and mortality. Although anemia often responds to combination antiretroviral therapy, many patients remain anemic despite therapy and such persistent anemia continues to negatively affect prognosis regardless of drug response. Anemia is also a common feature of normal aging. We postulate that the pathophysiology of anemia in HIV, especially that which persists in the face of combination antiretroviral therapy, is a reflection of underlying proinflammatory pathways that are also thought to contribute to anemia in the elderly, as well as other age-related chronic diseases such as cardiovascular disease and chronic obstructive pulmonary disease. This suggests that HIV induces inflammatory pathways that are associated with a pattern of accelerated aging and that anemia is a biomarker of these processes. A better understanding of the pathophysiology of HIV-related anemia may provide important entry points for improving the chronic manifestations of HIV-related disease.

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“…[8] The mechanisms potentially involved in the production of AAbs in the context of HIV infection include molecular mimicry, [9,10] dysregulation of the interaction between B and T lymphocytes, [11] and polyclonal B lymphocyte activation. Studies investigating this latter hypothesis did not find a significant relationship between polyclonal hypergammaglobulinemia and the presence of ANAs, ANCAs, or aPL, but these studies were mostly performed in the pre-highly active antiretroviral therapy (HAART) era and patients’ immunovirological status was not always well described.…”

Section: Introductionmentioning

confidence: 99%

Nonorgan-specific autoantibodies in HIV-infected patients in the HAART era

et al. 2017

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Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status.Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-β2glycoprotein1 (anti-β2GP1), and antineutrophil cytoplasmic antibodies (ANCAs). Clinically relevant AAbs were defined as ANAs with titers ≥1:160, anti-dsDNA or anti-ENA antibodies; aCL or anti-β2GP1 antibodies with a level ≥40 U/ml; and ANCAs reacting with proteinase 3 or myeloperoxidase.We included 92 patients (mean age 47 years, men 55%, sub-Saharan African background 55%, HAART 85%, mean CD4 lymphocyte count 611/mm3, viral load < 40 copies/mL 74%). At least 1 AAb was detected in 45% of patients, mostly ANAs (33%) and ANCAs (13%); 12% had ≥1 clinically relevant AAb. Above-normal IgG levels were found in 71% of patients. We found an inverse association between the presence of ≥1 AAb and CD4 lymphocyte count (P = 0.03) and between above-normal IgG levels and duration of virological control (P = 0.02) and non-sub-Saharan African background (P = 0.001).In sum, in HIV1-infected patients without any major concomitant illness in the HAART era, the prevalence of AAbs remains high but AAb patterns leading to high suspicion of autoimmune diseases are rather uncommon. AAb presence is associated with reduced CD4 lymphocyte count but not hypergammaglobulinemia.

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Fine Epitope Specificity of Anti-erythropoietin Antibodies Reveals Molecular Mimicry With HIV-1 p17 Protein: A Pathogenetic Mechanism for HIV-1–Related Anemia

Abstract: These results suggest that the main body of anti-Epo is directed against a functional domain of Epo, and that the presence of anti-Epo can be considered to be a result of a molecular mimicry mechanism, which is caused by the similarity between the Ep1 region and the p17 protein.

Cited by 35 publications

References 28 publications

Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000–2012

Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000–2012

Pathogenesis and clinical implications of HIV-related anemia in 2013

Nonorgan-specific autoantibodies in HIV-infected patients in the HAART era

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