Reactivation of Chagas-Mazza disease during treatment with infliximab

Vacas, Aldana Soledad; Gómez-Santana, L.V.; Torre, Ana Clara; Galimberti, Ricardo

doi:10.1590/abd1806-4841.20177346

Cited by 12 publications

(3 citation statements)

References 2 publications

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“…Lastly, since leukocyte influx towards target tissues is at least in part regulated by the interaction of cytokines and/or chemokines with ECM components, manipulating these interactions before the establishment of the cardiac damage may represent a potential therapeutic approach in chronic chagasic patients. Nevertheless, discordant results were reported in preclinical settings after blocking TNF-a (Bilate et al, 2007;Peŕez et al, 2009;Pereira et al, 2015), and the administration of an anti-TNF antibody to chronic chagasic patients correlated with Chagas disease reactivation (Vacas et al, 2017;Ringer et al, 2021), thus preventing its use in chagasic patients. By contrast, the administration of an anti-VLA-4 antibody attenuated experimental T. cruzi-driven brain inflammation, since it abrogated T-cell influx towards neuroendocrine tissues by blocking VLA-4/VCAM-1 and VLA-4/fibronectin interactions (Roffêet al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression

Berbert

González

Villar

et al. 2021

Front. Cell. Infect. Microbiol.

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Trypanosoma cruzi infection in humans leads to progression to chronic chagasic myocarditis (CCM) in 30% of infected individuals, paralleling T cell inflammatory infiltrates in the heart tissue. T-cell trafficking into the hearts of CCM patients may be modulated by in situ expression of chemotactic or haptotactic molecules, as the chemokine CXCL12, the cytokine tumor necrosis factor-alpha (TNF-α), and extracellular matrix proteins (ECM), such as fibronectin. Herein we evaluated the expression of fibronectin, CXCL12, and TNF-α in the myocardial tissue of T. cruzi seropositive (asymptomatic or with CCM), as well as seronegative individuals as healthy controls. Hearts from CCM patients exhibited enhanced expression of these three molecules. CXCL12 and TNF-α serum levels were also increased in CCM individuals. We then evaluated T lymphocytes from chronic chagasic patients by cytofluorometry, in terms of membrane expression levels of molecules involved in cell activation and cell migration, respectively, HLA-DR and the VLA-4 (very late antigen-4, being one integrin-type fibronectin receptor). Indeed, the expression of HLA-DR and VLA-4 was enhanced on T lymphocytes from chagasic patients, especially in the CCM group. To further approach the dynamics of T cell migratory events, we performed fibronectin-, TNF-α-, and CXCL12-driven migration. Peripheral blood mononuclear cells (PBMCs) and T cells from CCM patients presented an ex vivo enhanced migratory capacity driven by fibronectin alone when this ECM protein was placed in the membrane of transwell migration chambers. When TNF-α was previously placed upon fibronectin, we observed a further and significant increase in the migratory response of both PBMCs and T lymphocytes. Overall, these data suggest the existence in patients with chronic Chagas disease of a cardiac inflammatory infiltrate vector that promotes the recruitment and accumulation of activated T cells, driven in part by enhanced tissue expression of fibronectin and TNF-α, as well as the respective corresponding VLA-4 and TNF receptors.

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Section: Discussionmentioning

confidence: 99%

Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression

Berbert

González

Villar

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Indeed, experimental mouse models can mimic only few aspects of human pathologies and in some cases different parasite strains need to be employed as human-infecting strains might not be pathogenic in mice ( 134 – 136 ). Another important consideration that needs to be done in the context of parasitic diseases, is the indirect effect that mAb employed for the treatment of other disorders might have on host susceptibility to infections or on the reactivation of latent ones as observed, for instance, for latent leishmaniasis ( 137 ) or latent Chagas disease ( 138 ).…”

Section: Considerations and Conclusion: The Expert Point Of Viewmentioning

confidence: 99%

Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea?

et al. 2021

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Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this technology as a therapeutic approach for infectious diseases. The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of Clostridium difficile recurrence. Protozoan infections are often neglected diseases for which effective and safe chemotherapies are generally missing. In this context, drug resistance and drug toxicity are two crucial problems. The recent advances in bioinformatics, parasite genomics, and biochemistry methodologies are contributing to better understand parasite biology, which is essential to guide the development of new therapies. In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide.

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“…Cardiac involvement or worsening of previous cardiomyopathy may also occur [55]. Data on CD in rheumatology patients treated with biological therapies or JAK inhibitors remain sparse; however, a case of relapsed CD has been reported in a patient treated with infliximab, although the patient did not develop severe symptoms and relapse was detected via a higher quantifiable PCR result [56]. One case series looked at immunosuppressed patients with chronic CD and included three patients with autoimmune disorders treated with regimens that included biologics.…”

Section: Chagas Diseasementioning

confidence: 99%

The immunosuppressed traveler: infection risks with autoimmunity and immunosuppression, vaccinations, and general travel advice

Allen

Longley

Galloway

et al. 2020

Handbook of Systemic Autoimmune Diseases

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Reactivation of Chagas-Mazza disease during treatment with infliximab

Cited by 12 publications

References 2 publications

Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression

Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression

Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea?

The immunosuppressed traveler: infection risks with autoimmunity and immunosuppression, vaccinations, and general travel advice

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