Rev. Méd. RosaRio 88: 49-52, 2022

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CHAGAS DISEASE REACTIVATION IN RHEUMATOLOGIC PATIENTS: ASSOCIATION WITH

IMMUNOSUPPRESSIVE THERAPY AND HUMORAL RESPONSE

RingeR a, Ruffino JP, Leiva R, CuadRanti n, aRgento MC, MaRtínez Mf, RoLLa i, ChuLibeRt

s, CaRbone d, PaLatnik M, CoRtese Mn, LagRutta M, CóRdoba L, gonzáLez bf, PaCini Mf,

viLLaR sR, águiLa d, bottasso o, PéRez aR, abdaLa M.

Evidence for Chagas disease reactivation (CDR) (11.7%), exhibiting both positive Strout and PCR.

in rheumatologic patients under rheumatologic Symptomatic reactivation of CD (fever, asthenia,

treatments (RTs) is scarce. To screen and follow-up arthralgias, myalgias) occurred in two patients who

patients with rheumatic diseases and concomitant had previously been diagnosed with it. Regardless of

Chagas disease, under RT to detect CDR and to the diﬀerent RT, all patients who experienced CDR

describe a possible relationship between CDR and had previously received more than ≥ 20 mg/day of

speciﬁc RT. An observational, longitudinal, prospective, prednisone equivalent. Despite immunosuppression,

consecutive study was carried out between 2018 and patients with CDR exhibited increased levels of speciﬁc

020. Included patients were evaluated during the anti-T. cruzi and anti-SAPA antibodies, which decreased

follow-up for clinical and laboratorial manifestations after anti-parasitic treatment. CDR is possible in

of CDR. Direct blood parasitological examination rheumatologic patients, especially after receiving high

(

Strout method) and polymerase chain reaction (PCR) doses of corticosteroids. Since CDR symptoms may

were employed to diagnose CDR. e dynamic of mimic rheumatic disease activity, monitoring of Chagas

anti-T. cruzi–speciﬁc antibodies was also assessed by disease is highly recommended before, during and after

IHA and ELISA (total IgG and Anti-SAPA). Fifty-one immunosuppression.

patients were included (86% women). Rheumatoid

arthritis was the predominant disease (57%). Classic

DMARDs (86.3%) and corticosteroids (61%) were the

most frequent RT. CDR was developed in 6 patients

Clin Rheumatol 40: 2955-2963, 2021.

LEVELS OF ANTI-B13 ANTIBODIES OVER TIME IN A COHORT OF CHRONIC INFECTED BY

TRYPANOSOMA CRUZI. ITS RELATIONSHIP WITH SPECIFIC TREATMENT AND CLINICAL

STATUS

oLiveRa v, bizai ML, aRias e, suasnábaR s, bottasso o, MaRCiPaR i, fabbRo d.



eimmunodominantB13proteinofTrypanosoma with heart complaints. Two hundred twenty-eight

cruzi is found on the surface of trypomastigotes and serum samples from 76 chronically infected adults with

exhibits cross-reactivity with the human cardiac myosin an average follow-up of 24 years were analyzed. irty

heavy chain; for which antibodies against this parasitic of them had received trypanocidal treatment. Among

antigen may be involved in the development of disease treated patients, anti-B13 Ab levels in successive samples

pathology. In a cohort of chronically T. cruzi-infected showed a signiﬁcant decrease in reactivity as the years

adults, undergoing trypanocidal treatment, or not, we, after treatment increased (ANOVA test, p = 0.0049).

therefore, decided to evaluate the levels of anti-B13 At the end of the follow-up, 36.7% became nonreactive

antibodies (ELISA-B13) and its eventual relationship for ELISA B13.

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Rev. Méd. RosaRio 88: 49-52, 2022

Untreated patients did not have signiﬁcant variations in no signiﬁcant diﬀerences in anti-B13 antibodies when

the level of anti-B13 antibodies during follow-up. None comparing individuals without proven pathology with

of the treated patients had electrocardiographic changes those with chronic chagasic cardiomyopathy. Although

compatible with chronic chagasic cardiomyopathy, treatment with trypanocidal drugs was followed by

whereas 21.7% of those undergoing no treatment did decreased anti-B13 antibody levels, such assessment was

show such kind of pathological electrocardiogram unhelpful in diﬀerentiating the evolution of chronic

tracings. ELISA-B13 was reactive in all cases with heart chagasic heart disease.

involvement. Among untreated patients, there were

Acta Tropica 218: 105908, 2021.

TRYPANOCIDAL THERAPY AMONG CHILDREN INFECTED WITH CHRONIC INFECTION BY

TRYPANOSOMA CRUZI. SEROLOGICAL AND ELECTROCARDIOGRAPHIC CHANGES OVER A

MEAN TWENTY-FIVE-YEARS FOLLOW-UP PERIOD

suasnábaR s, oLiveRa Lv, aRias e, bizai ML, bottasso o, aRias e, fabbRo d.



is study compared the serological and electrocardiographic abnormalities was signiﬁcantly

electrocardiographic evolution among patients with reduced among treated patients (OR = 0.18, 95%

chronicT. cruziinfectiontreatedduringchildhoodorleft CI = 0.04-0.79; p = 0.023). Electrocardiographic

untreated. A retrospective cohort study was conducted abnormalities attributable to Chagas cardiomyopathy

during a mean follow-up period of 25 years in 82 were seen in 3 patients from the untreated group

patients: half of them underwent treatment (nifurtimox (complete right bundle branch block + left anterior

, benznidazole 33) before being 15 years old, whereas fascicular block, frequent ventricular extrasystole,

the other half remained untreated. During the follow- and left anterior fascicular block). e remarkable

up, negative seroconversion occurred in 92.7% of the seronegativization seen in Benznidazole and Nifurtimox

treated children, while all the untreated ones remained recipients underlines the parasiticidal eﬀect of both

positive for conventional serology. At baseline, 2 compounds. Such demonstration along with the fact

patients from each group had electrocardiographic that CCC-related alterations were only present in the

abnormalities. During the study period, 4/41 (9.75%) untreated group, reinforces the view of trypanocidal

and 9/41 (21.95%) of treated and untreated patients treatment in chronically T. cruzi-infected children as

displayed an altered electrocardiogram, respectively. decreasing the risk for cardiomyopathy development.

In multivariate analyses, the probability of developing

Acta Tropica 222: 106050, 2021.

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ENHANCED MIGRATORY CAPACITY OF T LYMPHOCYTES IN SEVERE CHAGASIC PATIENTS IS

CORRELATED WITH VLA-4 AND TNF-α EXPRESSION

beRbeRt LR, gonzáLez fb, viLLaR sR, vigLiano C, Lioi s, beLosCaR J, bottasso oa, siLva-

baRbosa sd, savino W, PéRez aR.

Trypanosoma cruzi infection in humans leads to VLA-4 was enhanced on T lymphocytes from chagasic

progression to chronic chagasic myocarditis (CCM) patients, especially in the CCM group. To further

in 30% of infected individuals, paralleling T cell approach the dynamics of T cell migratory events,

inﬂammatory inﬁltrates in the heart tissue. T-cell we performed ﬁbronectin-, TNF-α, and CXCL12-

traﬃcking into the hearts of CCM patients may be driven migration. Peripheral blood mononuclear cells

modulated by in situ expression of chemotactic or (PBMCs) and T cells from CCM patients presented

haptotactic molecules, as the chemokine CXCL12, an ex vivo enhanced migratory capacity driven by

the cytokine tumor necrosis factor-alpha (TNF-a), and ﬁbronectin alone when this ECM protein was placed

extracellular matrix proteins (ECM), such as ﬁbronectin. in the membrane of transwell migration chambers.

Herein we evaluated the expression of ﬁbronectin, When TNF-α was previously placed upon ﬁbronectin,

CXCL12, and TNF-α in the myocardial tissue of T. we observed a further and signiﬁcant increase in the

cruzi seropositive (asymptomatic or with CCM), as well migratory response of both PBMCs and T lymphocytes.

as seronegative individuals as healthy controls. Hearts Overall, these data suggest the existence in patients

from CCM patients exhibited enhanced expression of with chronic Chagas disease of a cardiac inﬂammatory

these three molecules. CXCL12 and TNF-α serum inﬁltrate vector that promotes the recruitment and

levels were also increased in CCM individuals. We then accumulation of activated T cells, driven in part by

evaluated T lymphocytes from chronic chagasic patients enhanced tissue expression of ﬁbronectin and TNF-α,

by cytoﬂuorometry, in terms of membrane expression as well as the respective corresponding VLA-4 and TNF

levels of molecules involved in cell activation and cell receptors.

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

Front Cell Infect Microbiol 11 (Article 713150), 2021.

https://doi.org/10.3389/fcimb.2021.713150.

INCREASED LEVELS OF CIRCULATING LPS DURING TUBERCULOSIS PREVAILS IN PATIENTS

WITH ADVANCED PULMONARY INVOLVEMENT

gaLLuCCi g, santuCCi n, diaz aRiana, bongiovanni b, béRtoLa d, gaRdeñez W, Rassetto M,

bay ML, bottasso o, d´attiLio L.

Our earlier studies in tuberculosis (TB) patients circulating lipopolysaccharides (LPS). Consequently,

indicate that in those where the process evolves we quantiﬁed LPS levels in TB patients, with diﬀerent

to a larger pulmonary involvement, the immune degrees of pulmonary involvement, and controls (Co)

endocrine response may promote an unfavorable and analyzed the possible relationship between LPS and

environment. Chronic infectious diseases, and their inﬂammatory mediators i.e., C reactive protein (CRP),

persistent proinﬂammatory response, may aﬀect interleukin 6 (IL-6) and Interferon gamma (IFN-γ),

mucosal barriers integrity favoring the translocation Erythrocyte Sedimentation Rate (ESR), steroid

of gastrointestinal bacteria, leading to an increase of hormones (Cortisol and Dehydroepiandrosterone,

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Rev. Méd. RosaRio 88: 49-52, 2022

DHEA), and inﬂammatory transcripts from peripheral Only in PBMC from severe cases was mRNA for IL-

blood mononuclear cells (IL-1β, IL-6, IFN-γ). LPS was 1β increased. Correlation analysis showed that levels

assessed by the Limulus amoebocyte lysate assay and of LPS from severe patients were positively associated

the ELISA technique was used to quantify hormones with IL-6 and IFN-γ plasma concentrations and with

and cytokines in the plasma samples. Cytokine IL-1β transcripts, while IL-6 had a positive correlation

transcripts from PBMC were evaluated by qRT-PCR. with the cortisol/DHEA ratio. e higher levels of

Nonparametric tests were used. LPS levels were increased circulating LPS during progressive TB may emerge as

inTB patients, as did levels of CRP, IL-6, IFN-γ, cortisol a contributing factor for the persistence of the greater

and ESR. Severe patients had the highest amounts immune endocrine imbalance distinctive of advanced

of circulating LPS; with moderate and severe cases disease, which might suggest a vicious cycle among LPS,

showing much higher levels of CRP, ESR, IL-6, IFN-γ inﬂammation and endocrine imbalance.

and cortisol/DHEA ratio, as an endocrine imbalance.

PLoS One 16(9): e0257214, 2021

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