Toxoplasma-SPECIFIC IgG SUBCLASS ANTIBODY RESPONSE IN CEREBROSPINAL FLUID SAMPLES FROM PATIENTS WITH CEREBRAL TOXOPLASMOSIS

Nascimento, Fernanda S.; Suzuki, Lisandra Akemi; Branco, Nilson; Franco, Regina Maura Bueno; Andrade, Paula Durante; Costa, Sandra Cecı́lia Botelho; Pedro, Matheus Kahakura Franco; Rossi, Claudio

doi:10.1590/s0036-46652015000500013

Cited by 4 publications

(1 citation statement)

References 22 publications

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“…The role of the IgG subclasses as an early diagnostic tool, indicator of parasite clearance or predictor of disease prognosis has been assessed in other protozoan infections including malaria [ 51 – 54 ] and toxoplasmosis [ 55 , 56 ]. In visceral leishmaniasis, the level of IgG1 response has been shown to be a potential therapeutic marker, principally in India; patients considered to be cured had significantly lower levels of anti- Leishmania IgG1 compared to those with treatment failure or relapse [ 57 , 58 ], possibly due the lack of sustained antigenic stimulus associated with successful chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

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Background Chagas disease remains a significant public health problem in Latin America. There are only two chemotherapy drugs, nifurtimox and benznidazole, and both may have severe side effects. After complete chemotherapy of acute cases, seropositive diagnosis may revert to negative. However, there are no definitive parasitological or serological biomarkers of cure. Methods Following a pilot study with seven Bolivian migrants to Spain, we tested 71 serum samples from chronic patients (mean age 12.6 years) inhabiting the Argentine Chaco region. Benznidazole chemotherapy (5–8 mg/kg day, twice daily for 60 days) was administered during 2011–2016. Subsequently, pre-and post-chemotherapy serum samples were analysed in pairs by IgG1 and IgG ELISA using two different antigens and Chagas Sero K-SeT rapid diagnostic tests (RDT). Molecular diagnosis by kDNA-PCR was applied to post-treatment samples. Results Pilot data demonstrated IgG1 antibody decline in three of seven patients from Bolivia 1 year post-treatment. All Argentine patients in 2017 (averaging 5 years post-treatment), except one, were positive by conventional serology. All were kDNA-PCR-negative. Most (91.5%) pre-treatment samples were positive by the Chagas Sero K-SeT RDT, confirming the predominance of TcII/V/VI. IgG1 and IgG of Argentine patients showed significant decline in antibody titres post-chemotherapy, with either lysate (IgG, P = 0.0001, IgG1, P = 0.0001) or TcII/V/VI peptide antigen (IgG, P = 0.0001, IgG1, P = 0.0001). IgG1 decline was more discriminative than IgG. Antibody decline after treatment was also detected by the RDT. Incomplete treatment was associated with high IgG1 post-treatment titres against lysate (P = 0.013), as were IgG post-treatment titres to TcII/V/VI peptide (P = 0.0001). High pre-treatment IgG1 with lysate was associated with Qom ethnicity (P = 0.045). No associations were found between gender, age, body mass index and pre- or post-treatment antibody titres. Conclusions We show that following chemotherapy of early chronic Chagas disease, significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure. Graphical abstract We show that following chemotherapy of early chronic Chagas disease, a significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure.

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Section: Discussionmentioning

confidence: 99%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

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The Gut Microbiome Affects Human Mood and Behavior

Villa

Sánchez-Pérez

2021

Developmental Biology in Prokaryotes and Lower Eukaryotes

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Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii

et al. 2022

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In order to evaluate and compare the specific immune response of pregnant women (PW) chronically infected with Toxoplasma gondii, with and without gestational diabetes mellitus (GDM), and the humoral response of their respective newborns (NB), the study was carried out on 81 PW (34 GDM and 47 controls) from whose medical records the results of the oral glucose tolerance test (OGTT) were obtained, and blood samples were collected at the third trimester of pregnancy; also, on 45 NBs (20 GDM and 25 controls) from whom umbilical cord blood samples were obtained. Humoral immunity was analyzed by measuring anti-T. gondii total IgG, IgG subclasses and IgG avidity. To evaluate cellular immunity, peripheral blood mononuclear cells (PBMC) from 32 PW (16 GDM and 16 controls) were cultured, supernatant cytokines were determined, and flow cytometry was performed to analyze the expression at lymphocytes of surface molecules, cytokines and transcription factors. All PW and NBs were positive for total IgG, and the prevalent subclass was IgG1. There was a negative correlation between the OGTT glycemia of PW and the levels of total IgG, IgG1 and IgG avidity. The IgG avidity of the GDM group was significantly lower than the control group. Patients from the GDM group had a higher number of T lymphocytes expressing markers of cell activation and exhaustion (CD28 and PD-1). In the presence of T. gondii soluble antigen (STAg) the amount of CD4+ T cells producing IFN-γ, IL-10 and IL-17 was significantly lower in the GDM group, while there was no difference between groups in the number of CD4+ CD25HighFOXP3+LAP+ functional Treg cells. Additionally, under STAg stimulus, the secretion of IL-17, IL-4, TNF and IL-2 cytokines at PBMCs culture supernatant was lower in the GDM group. In conclusion, there was a correlation between the increase in blood glucose and the decrease in levels of anti-T. gondii antibodies, associated with the decreased IgG avidity in patients who develop GDM. Also, the GDM group had decreased immune responses in Th1, Th2 and Th17 profiles, suggesting an association between GDM and the negative modulation of the humoral and cellular immune responses against T. gondii.

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Toxoplasma-SPECIFIC IgG SUBCLASS ANTIBODY RESPONSE IN CEREBROSPINAL FLUID SAMPLES FROM PATIENTS WITH CEREBRAL TOXOPLASMOSIS

Cited by 4 publications

References 22 publications

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

The Gut Microbiome Affects Human Mood and Behavior

Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii

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