Atypical memory B-cells and autoantibodies correlate with anemia during Plasmodium vivax complicated infections

Rivera-Correa, Juan; Yasnot, María Fernanda; Tovar, Nubia Catalina; Easton, Alice V.; Rodrı́guez, Ana

doi:10.1371/journal.pntd.0008466

Cited by 21 publications

(17 citation statements)

References 40 publications

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“…Plasma samples from complicated and uncomplicated P. vivax infections and controls were collected from patients recruited at Hospital San Jerónimo of Monteria and Hospital San José of Tierralta, Córdoba, Colombia, between 2017 and 2019 as described before ( Rivera-Correa et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

et al. 2021

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High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.

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Section: Methodsmentioning

confidence: 99%

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

et al. 2021

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“…A consequence of the production of anti‐PS Abs is the removal of uninfected RBCs that express PS on their surface in the spleen, thereby contributing to the anemia associated with this infection 141 . Anti‐PS Abs may contribute to the anemia seen with P. falciparum and P. vivax infection, as IgG auto‐Abs against normal RBCs are found at an increased quantity in patients with anemia and are inversely correlated to hemoglobin levels 144–147 . Abs against PS are not the only auto‐Abs induced by Plasmodium infection, as Abs against nuclear and brain Ags and ssDNA are often commonly found in patients in endemic regions 148–150 .…”

Section: Generation Of Protective Immune Responsesmentioning

confidence: 99%

The spleen: “epicenter” in malaria infection and immunity

Ghosh

Stumhofer

2021

Journal of Leukocyte Biology

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The spleen is a complex secondary lymphoid organ that plays a crucial role in controlling bloodstage infection with Plasmodium parasites. It is tasked with sensing and removing parasitized RBCs, erythropoiesis, the activation and differentiation of adaptive immune cells, and the development of protective immunity, all in the face of an intense inflammatory environment. This paper describes how these processes are regulated following infection and recognizes the gaps in our current knowledge, highlighting recent insights from human infections and mouse models.

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“…Autoimmunity has been suggested to play an important role in promoting pathology during trypanosome infection [3,26]. The objective of this study was to assess whether autoimmunity against PS by atypical B-cells had a role in acute anemia during infection with trypanosomes, hence expanding our previous studies of acute anemia during malaria [7][8][9][10][11][12]. During malaria, autoimmunity against PS is a transient phenomenon that contributes to acute-phase anemia through clearance of RBCs mediated by the binding of anti-PS autoantibodies to exposed PS on RBC [10].…”

Section: Discussionmentioning

confidence: 96%

“…ABCs were first discovered in aged mice and mouse models of autoimmunity, and have been the hallmark of different human autoimmune diseases [ 17 , 18 ]. Our previous work has established a key role for ABCs in promoting malarial anemia, through the secretion of anti-PS and other autoantibodies, in both mice and patients [ 8 , 9 , 11 , 12 ]. These studies raised the question whether ABCs could be playing a similar role during other highly inflammatory infections.…”

Section: Discussionmentioning

confidence: 99%

“…Autoimmune anemia has been a well-documented complication during different infections but has been complex to understand due to its multi-factorial etiology [5]. During malaria, autoimmune antibodies targeting the membrane lipid phosphatidylserine (PS) exposed in the membrane of uninfected erythrocytes promote their lysis and premature clearance in both mice and humans, aggravating anemia [6][7][8][9][10][11]. These anti-PS autoantibodies are secreted primarily by autoimmune B-cells (called atypical B-cells or Age-Associated B-cells, ABCs), that are characterized by the expression of the transcription factor T-bet and the integrin CD11c, and associated with anemia during malaria [12].…”

Section: Introductionmentioning

confidence: 99%

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Autoimmunity to phosphatidylserine and anemia in African Trypanosome infections

et al. 2021

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Anemia caused by trypanosome infection is poorly understood. Autoimmunity during Trypanosoma brucei infection was proposed to have a role during anemia, but the mechanisms involved during this pathology have not been elucidated. In mouse models and human patients infected with malaria parasites, atypical B-cells promote anemia through the secretion of autoimmune anti-phosphatidylserine (anti-PS) antibodies that bind to uninfected erythrocytes and facilitate their clearance. Using mouse models of two trypanosome infections, Trypanosoma brucei and Trypanosoma cruzi, we assessed levels of autoantibodies and anemia. Our results indicate that acute T. brucei infection, but not T. cruzi, leads to early increased levels of plasma autoantibodies against different auto antigens tested (PS, DNA and erythrocyte lysate) and expansion of atypical B cells (ABCs) that secrete these autoantibodies. In vitro studies confirmed that a lysate of T. brucei, but not T. cruzi, could directly promote the expansion of these ABCs. PS exposure on erythrocyte plasma membrane seems to be an important contributor to anemia by delaying erythrocyte recovery since treatment with an agent that prevents binding to it (Annexin V) ameliorated anemia in T. brucei-infected mice. Analysis of the plasma of patients with human African trypanosomiasis (HAT) revealed high levels of anti-PS antibodies that correlated with anemia. Altogether these results suggest a relation between autoimmunity against PS and anemia in both mice and patients infected with T. brucei.

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Atypical memory B-cells and autoantibodies correlate with anemia during Plasmodium vivax complicated infections

Cited by 21 publications

References 40 publications

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

The spleen: “epicenter” in malaria infection and immunity

Autoimmunity to phosphatidylserine and anemia in African Trypanosome infections

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