Autoantibodies during infectious diseases: Lessons from malaria applied to COVID-19 and other infections

Rivera-Correa, Juan; Rodrı́guez, Ana

doi:10.3389/fimmu.2022.938011

Cited by 13 publications

(5 citation statements)

References 78 publications

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“…Autoimmune activity contributing to prothrombotic and inflammatory processes in the context of systemic infections has become increasingly appreciated (30,65). Here, we evaluated whether prothrombotic autoimmune processes play a role in the pathogenesis of pediatric malaria.…”

Section: Discussionmentioning

confidence: 99%

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Vera,

Kessler,

Harawa

et al. 2024

Journal of Clinical Investigation

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Background. Features of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM.Methods. Plasma from children with uncomplicated malaria (UM, n=124) and CM (n=136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-Platelet Factor 4/polyanion (anti-PF4/P), anti-Phospholipid, anti-Phosphatidylserine, anti-Myeloperoxidase, anti-Proteinase 3, anti-dsDNA, anti-Beta-2-Glycoprotein I (β2GPI), and anti-Cardiolipin. Non-malarial coma (NMC, n=49) and healthy controls (HC, n=56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses.Results. Median anti-PF4/P and anti-PS IgG levels were elevated with malaria infection relative to HC (p<0.001) and NMC (PF4/P: p<0.001). Anti-PF4/P IgG levels were elevated in CM (median=0.27, IQR: 0.19-0.41) compared to UM (median=0.19, IQR: 0.14-0.22, p=<0.0001). Anti-PS IgG levels did not differ between UM and CM (p=0.39). When CM cases were stratified by malaria retinopathy (Ret) status, levels of anti-PF4/P IgG correlated negatively with peripheral platelet count in Ret+ CM cases (Rs= 0.201, p=0.04) and associated positively with mortality (OR=15.2, 95% CI: 1.02 -275, p=0.048).Plasma from CM patients induced greater platelet activation in an ex-vivo assay relative to plasma from UM patients (p=0.02), and the observed platelet activation was associated with anti-PF4/P IgG levels (Rs= 0.293, p=0.035). Conclusions.Thrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.

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Section: Discussionmentioning

confidence: 99%

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Vera,

Kessler,

Harawa

et al. 2024

Journal of Clinical Investigation

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“…There is accumulating evidence of autoantibody generation during malaria and other infectious diseases, while their potential pathological role remains insufficiently known [11]. Autoimmune hemolytic anemia, antiphospholipid antibodies, new fluorescence type of ANA, and different ANCA patterns had previously been described in patients suffering from malaria [12][13][14][15].…”

Section: Discussionmentioning

confidence: 99%

Myositis-specific autoantibodies in a non-traveler, patient from a non-endemic country, with Plasmodium vivax malaria

Stojanovic,

Barac,

Miskovic

et al. 2023

J Infect Dev Ctries

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Introduction: Autoantibodies (AAb) are a hallmark of immune-mediated inflammatory diseases. Malaria is a parasitic disease caused by Plasmodium protozoa. Individuals with malaria may present with a wide range of symptoms. It is frequently linked to the development of different AAb. Case description: A 35-year-old male presented with repeated episodes of fever, malaise, myalgia, dark urine, and yellowish sclera. Initial diagnostic workup revealed severe Coombs-positive anemia, increased C-reactive protein, and procalcitonin, pathological liver tests, high concentration of serum IgE, IgG, IgM, IgA, positive antinuclear antibodies (ANA), and positive antineutrophil cytoplasmatic antibodies (ANCA). In addition, myositis-specific antibodies directed to polymiositis-scleroderma 75 protein (PmScl75), threonyl-tRNA synthetase (PL-7), alanyl-tRNA synthetase (PL-12), Mi-2 antigen (Mi-2), Ku DNA helicase complex (Ku), signal recognition particle (SRP), and antiaminoacyl tRNA synthetase (EJ) were detected. The patient was suspected of having systemic lupus erythematosus and sent to the Clinic of Allergy and Immunology for further evaluation and treatment. A peripheral blood film examined by the hematologist during an episode of fever revealed intra-erythrocytic parasitic forms of Plasmodium vivax (P. vivax). After being diagnosed with P. vivax malaria, he was transferred to the Clinic for Infective and Tropical Diseases. The therapy consisted of artesunate/mefloquine and prednisone led to a complete clinical recovery and autoantibodies gradually disappeared. Conclusions: Malaria would not normally be considered during the initial diagnostic workup in a non-traveler and a patient from a non-endemic country. However, a thorough parasitic evaluation in patients presenting with a broad range of autoantibodies might be of particular importance.

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“…Finally, it has been observed that antibodies produced during an infection can trigger neuropsychiatric complications due to a cross-reaction in which antibodies recognize pathogen antigens but may also recognize self-antigens[ 68 , 69 ]. It has been proposed that genetic factors of the host and infectious agent influence the development of these complications[ 70 ].…”

Section: Other Immunological Mechanisms Inducing Psychiatric Complica...mentioning

confidence: 99%

How inflammation influences psychiatric disease

Ferat-Osorio,

Maldonado-García,

Pavón

2024

World J Psychiatry

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Recent studies highlight the strong correlation between infectious diseases and the development of neuropsychiatric disorders. In this editorial, we comment on the article “Anti-infective therapy durations predict psychological stress and laparoscopic surgery quality in pelvic abscess patients” by Zhang et al , published in the recent issue of the World Journal of Psychiatry 2023; 13 (11): 903-911. Our discussion highlighted the potential consequences of anxiety, depression, and psychosis, which are all linked to bacterial, fungal, and viral infections, which are relevant to the impact of inflammation on the sequelae in mental health as those we are observing after the coronavirus disease 2019 pandemic. We focus specifically on the immune mechanisms triggered by inflammation, the primary contributor to psychiatric complications. Importantly, pathophysiological mechanisms such as organ damage, post-injury inflammation, and infection-induced endocrine alterations, including hypocortisolism or autoantibody formation, significantly contribute to the development of chronic low-grade inflammation, promoting the emergence or development of psychiatric alterations in susceptible individuals. As inflammation can have long-term effects on patients, a multidisciplinary treatment plan can avoid complications and debilitating health issues, and it is crucial to recognize and address the mental health implications.

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Autoantibodies during infectious diseases: Lessons from malaria applied to COVID-19 and other infections

Cited by 13 publications

References 78 publications

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Myositis-specific autoantibodies in a non-traveler, patient from a non-endemic country, with Plasmodium vivax malaria

How inflammation influences psychiatric disease

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