Humoral immune response to cruzipain and cardiac dysfunction in chronic Chagas disease

Duschak, Vilma G.; Riarte, Adelina; Segura, Elsa L.; Laucella, Susana A.

doi:10.1016/s0165-2478(01)00255-3

Cited by 32 publications

(24 citation statements)

References 23 publications

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“…It is possible that the decrease in reactivity after 70 days could due to immunoglobulin deposit in heart tissue [20]. Interestingly, in human Chagas disease, antibodies specific to particular Cz epitopes were associated to severe cardiac damage [16,43]. Taken together, our results suggest that the higher viability and activation ability of B cells could improve the effectiveness of these cells as APCs, autoantibody producer and amplify and sustain the autoimmune response in Cz immune BALB/c mice [17,18,44].…”

Section: Discussionmentioning

confidence: 72%

“…In this context, Leon et al [11] reported that humoral and cellular cardiac autoimmunity is developed during acute T. cruzi infection in the genetically susceptible host. Accumulating experimental evidence suggests that cruzipain (Cz), a major cysteine protease of the parasite [12,13], plays an important role in the disease's progression [14][15][16]. We previously reported that the immunization of BALB/c and C57BL/6 (B6) mice with Cz generated a heart autoimmune response and tissue damage only in BALB/c mice [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity

Pellegrini

Silva

Arocena

et al. 2011

Med Microbiol Immunol

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Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and represents the most common infectious myocarditis worldwide. Autoimmunity is one of the mechanisms contributing to its pathogenesis. Although the cellular interactions that promote this autoimmune response are still poorly understood, several studies have demonstrated a key role for B lymphocytes since they secrete antibodies, cytokines and present antigens. Recently, we reported that immunization with cruzipain, an immunodominant T. cruzi antigen, induces a higher activation state in B cells from BALB/c mice (susceptible to cardiac autoimmunity) than B lymphocytes from C57BL/6 (a resistant strain). Here, we focused on the study of B cell survival in both mouse strains after cruzipain immunization and demonstrated an increased survival rate of B cells from BALB/c compared to C57BL/6 mice. This phenomenon was associated with a decreased expression of Fas/FasL and an increased expression of anti-apoptotic Bcl-2/Bcl-xL proteins. With the purpose to gain more knowledge about the mechanisms involved, we found that IL-4 produced by BALB/c B cells played a key role in the survival in an autocrine way whereas the addition of this bioactive cytokine rescued C57BL/6 B lymphocytes from apoptosis. Our findings suggest that in the absence of infection, both enhanced B cell activation induced by the immunization with a single parasite antigen and insufficient negative regulation can potentially contribute to autoimmunity seen in cruzipain immune BALB/c mice.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity

Pellegrini

Silva

Arocena

et al. 2011

Med Microbiol Immunol

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“…Strips soaked in sodium acetate buffer served as controls. After treatment and intensive washing, Western blotting assays were performed as previously described [18]. Proteinase treatment was done by incubation of allergenic extracts with proteinase K (1 µg/ml) for 1 h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Antigenicity and Immunocrossreactivity of Orange Tree Pollen and Orange Fruit Allergenic Extracts

Irañeta

Seoane

Laucella

et al. 2005

Int Arch Allergy Immunol

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Background: It is important to study the crossreactivity between orange tree pollen (OTPE) and orange fruit (OFE) due to the high incidence of pollen/food-related allergies worldwide. The aim of the present study was to determine the antigenic relationship between OTPE and OFE. Methods: OTPE and OFErabbit antisera as well as sera from patients allergic to OTPE and OFE were comparatively applied in IgG- and/or IgE-specific ELISA inhibition, crossover or inhibition immunoblotting assays using OTPE and OFE allergenic extracts as solid phase. Periodate and proteinase K treatments were used for carbohydrate and protein depletion, respectively. Results: The antigenicity of OTPE and the presence of common structures between OTPE and OFE extracts were demonstrated by rabbit IgG-specific ELISA inhibition and crossover immunoblotting assays. A 30-kDa protein, common target of the IgE response on OTPE, OFE and mandarin extract, but absent in lemon extract, was identified by ELISA and immunoblot inhibition assays in patients suffering from primary sensitization to OTPE in the context of occupational exposure. Moreover, biochemical treatments showed that antigenic epitopes on the 30-kDa protein contain polypeptidic but no carbohydrate moieties. Conclusions: The antigenicity of OTPE, the presence of common antigenic determinants between pollen and citrus fruits and an IgE-specific crossreactive protein band of 30 kDa sharing carbohydrate-free epitopes were described. After isolation and purification, this common antigen might be useful for allergen immunotherapy in pollen/fruit-related allergic patients.

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“…(Leon & Engman, 2001) Among these antigens we should mention cruzipain, (Giordanengo et al, 2000;Goin et al, 1999;Duschak et al, 2001) sulfo-cerebrosides (Avila et al, 1993) and the ribosomal protein TcP2. (Levitus et al, 1991) Precursor works had described that this ribosomal antigen that shares the C terminal region with its homologous from humans, generated autoimmune antibodies, whose concentration was increased in patients who had developed chagasic cardiopathy.…”

Section: Chronic Infection Monitoringmentioning

confidence: 99%

Advances in Serological Diagnosis of Chagas' Disease by Using Recombinant Proteins

Marcipar¹,

Lagier²

2012

Current Topics in Tropical Medicine

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Humoral immune response to cruzipain and cardiac dysfunction in chronic Chagas disease

Cited by 32 publications

References 23 publications

Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity

Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity

Antigenicity and Immunocrossreactivity of Orange Tree Pollen and Orange Fruit Allergenic Extracts

Advances in Serological Diagnosis of Chagas' Disease by Using Recombinant Proteins

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