Antigenuria in chronic chagasic patients detected by a monoclonal antibody raised against Trypanosoma cruzi

Katzin, Alejandro M.; Alves, Maria Júlia M.; Abuin, G; Colli, Walter

doi:10.1016/0035-9203(89)90497-5

Cited by 8 publications

(8 citation statements)

References 12 publications

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“…The presence of T. cruzi antigens in urine was previously reported by other research groups with sensitivity of 60-100%. 36,50,51 The molecular weight of the antigenic bands detected in the urine samples of the infected pigs are similar to those detected by our group in other animal models and in humans. 37 The presence of soluble fragments of parasitic DNA (188 bp) in urine can be explained by small fragments of DNA of parasites that have died by apoptosis and subsequently crossed the glomerulus barrier in the kidney.…”

Section: Discussionsupporting

confidence: 84%

Domestic Pig (Sus scrofa) as an Animal Model for Experimental Trypanosoma cruzi Infection

Yauri

Castro-Sesquen

Verástegui

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Pigs were infected with a Bolivian strain of Trypanosoma cruzi (genotype I) and evaluated up to 150 days postinoculation (dpi) to determine the use of pigs as an animal model of Chagas disease. Parasitemia was observed in the infected pigs during the acute phase (15-40 dpi). Anti-T.cruzi immunoglobulin M was detected during 15-75 dpi; high levels of anti-T.cruzi immunoglobulin G were detected in all infected pigs from 75 to 150 dpi. Parasitic DNA was observed by western blot (58%, 28/48) and polymerase chain reaction (27%, 13/48) in urine samples, and in the brain (75%, 3/4), spleen (50%, 2/4), and duodenum (25%, 1/4), but no parasitic DNA was found in the heart, colon, and kidney. Parasites were not observed microscopically in tissues samples, but mild inflammation, vasculitis, and congestion was observed in heart, brain, kidney, and spleen. This pig model was useful for the standardization of the urine test because of the higher volume that can be obtained as compared with other small animal models. However, further experiments are required to observe pathological changes characteristic of Chagas disease in humans.

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Section: Discussionsupporting

confidence: 84%

Domestic Pig (Sus scrofa) as an Animal Model for Experimental Trypanosoma cruzi Infection

Yauri

Castro-Sesquen

Verástegui

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…Urinary T. cruzi antigens have been shown to correspond to glycoproteins [16], proteins belonging to the transferrin family [20], parasite tubulin [22] or cruzipain C-terminal extension [36]. However, these observations have never been widely exploited for the diagnosis of Chagas disease.…”

Section: Discussionmentioning

confidence: 99%

“…Soluble T. cruzi antigens with molecular weights of 150–160 kDa [15], 100 kDa [16], [17], 90–80 kDa [18], 80 kDa [16], [18]–[21], 70–65 kDa [18], 55–50 kDa [22], 55–45 kDa [18], 55 kDa [21], 50 kDa [17], and 40–35 kDa [18] have been reported in urine from animals and patients with Chagas disease. Although T. cruzi antigens in urine were presumed to derive from the systemic circulation [16], [17], amastigote nests have been demonstrated in kidney tissue of humans [23] and animals [24]–[26] and in the bladder of animals [27].…”

Section: Introductionmentioning

confidence: 99%

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Detection of Soluble Antigen and DNA of Trypanosoma cruzi in Urine Is Independent of Renal Injury in the Guinea Pig Model

et al. 2013

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The diagnosis of Chagas disease in humans is generally limited to the detection of specific antibodies. Detection of T. cruzi antigens in urine has been reported previously, but is not used in the diagnosis. In this study, soluble T. cruzi antigens and DNA were detected in urine samples and were associated with kidney injury and systemic detection of the parasite. We used 72 guinea pigs infected with T. cruzi Y strain and 18 non-infected guinea pigs. Blood, kidney, heart and urine samples were collected during the acute phase and chronic phase. Urine samples were concentrated by ultrafiltration. Antigens were detected by Western Blot using a polyclonal antibody against trypomastigote excretory-secretory antigen (TESA). T. cruzi DNA was detected by PCR using primers 121/122 and TcZ1/TcZ2. Levels of T. cruzi DNA in blood, heart and kidney were determined by quantitative PCR. T. cruzi antigens (75 kDa, 80 kDa, 120 kDa, 150 kDa) were detected in the acute phase (67.5%) and the chronic phase (45%). Parasite DNA in urine was detected only in the acute phase (45%). Kidney injury was characterized by high levels of proteinuria, kidney injury molecule-1 (KIM-1) and urea, and some histopathological changes such as inflammation, necrosis, fibrosis and scarce parasites. The detection of antigens and DNA in urine was associated with the presence of parasite DNA in blood and heart and with high levels of parasite DNA in blood, but not with the presence of parasite in kidney or kidney injury. These results suggest that the detection of T. cruzi in urine could be improved to be a valuable method for the diagnosis of Chagas disease, particularly in congenital Chagas disease and in immunocompromised patients.

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“…T. cruzi is an intracellular parasite and like other intracellular pathogens, has been shown to secrete parasite proteins into the host milieu [22]–[24]. These T .…”

Section: Introductionmentioning

confidence: 99%

Aptamer Based, Non-PCR, Non-Serological Detection of Chagas Disease Biomarkers in Trypanosoma cruzi Infected Mice

et al. 2014

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Chagas disease affects about 5 million people across the world. The etiological agent, the intracellular parasite Trypanosoma cruzi (T. cruzi), can be diagnosed using microscopy, serology or PCR based assays. However, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. It is well documented that several parasite proteins called T. cruzi Excreted Secreted Antigens (TESA), are released into the blood of an infected host. These circulating parasite antigens could thus be used as highly specific biomarkers of T. cruzi infection. In this study, we have demonstrated that, using a SELEx based approach, parasite specific ligands called aptamers, can be used to detect TESA in the plasma of T. cruzi infected mice. An Enzyme Linked Aptamer (ELA) assay, similar to ELISA, was developed using biotinylated aptamers to demonstrate that these RNA ligands could interact with parasite targets. Aptamer L44 (Apt-L44) showed significant and specific binding to TESA as well as T. cruzi trypomastigote extract and not to host proteins or proteins of Leishmania donovani, a related trypanosomatid parasite. Our result also demonstrated that the target of Apt-L44 is conserved in three different strains of T. cruzi. In mice infected with T. cruzi, Apt-L44 demonstrated a significantly higher level of binding compared to non-infected mice suggesting that it could detect a biomarker of T. cruzi infection. Additionally, Apt-L44 could detect these circulating biomarkers in both the acute phase, from 7 to 28 days post infection, and in the chronic phase, from 55 to 230 days post infection. Our results show that Apt-L44 could thus be used in a qualitative ELA assay to detect biomarkers of Chagas disease.

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Antigenuria in chronic chagasic patients detected by a monoclonal antibody raised against Trypanosoma cruzi

Cited by 8 publications

References 12 publications

Domestic Pig (Sus scrofa) as an Animal Model for Experimental Trypanosoma cruzi Infection

Domestic Pig (Sus scrofa) as an Animal Model for Experimental Trypanosoma cruzi Infection

Detection of Soluble Antigen and DNA of Trypanosoma cruzi in Urine Is Independent of Renal Injury in the Guinea Pig Model

Aptamer Based, Non-PCR, Non-Serological Detection of Chagas Disease Biomarkers in Trypanosoma cruzi Infected Mice

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