Skip to main content

Advertisement

SpringerLink
Log in

IgG Autoantibodies Induced by T. cruzi During Pregnancy: Correlation with Gravidity Complications and Early Outcome Assessment of the Newborns

  • Published:
Maternal and Child Health Journal Aims and scope Submit manuscript

Abstract

Objective The aim of the present research was to evaluate the correlation of vertically transmitted IgG antibodies induced by T. cruzi and newborn early outcome assessment, mainly birth weight and gestational age. Methods We performed a cross-sectional study with 183 pregnant women (64 with asymptomatic Chagas disease) and their newborns. Both were subjected to complete clinical examination. Peripheral parasitemia was assessed in mother and neonates by parasite detection through microscopic examination of the buffycoat from mother’s peripheral and cord blood. Antibodies induced by T. cruzi, such as anti-FRA, anti-B13, anti-p2β and anti-T. cruzi were assessed by immunoassay. Birth weight, general condition evaluation by APGAR Score and gestational age by Capurro Score, were determined in newborns. Results The rate of stillbirth background and pregnancy-induced hypertension were higher in patients with Chagas disease (p = 0.01 and p = 0.02, respectively). Parasitemia was detectable in 17 mothers and 4 newborns. The newborns of mothers with detectable parasitemia presented decreased gestational age (p = 0.006) and body weight (p = 0.04). Mostly all the mothers with Chagas disease and all their newborns have positive values of antibodies induced by T. cruzi; however, only anti-p2β showed to be related to the presence of complication during pregnancy (OR 2.35, p = 0.036), and to low birth weight (OR 1.55, p = 0.02). Conclusions Low birth weight and decreased postnatal estimation of maturity were related to detectable parasitemia in the mother. Also, vertical transmission of T. cruzi-induced autoantibodies might have clinical implication in newborns given the negative association between anti-p2β values and weight.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Coura, J. R., & Viñas, P. A. (2010). Chagas disease: A new worldwide challenge. Nature, 465(7301), S6–S7.

    Article  PubMed  Google Scholar 

  2. Organización Panamericana de la salud. (2006). Estimación cuantitativa de la enfermedad de Chagas en las Américas. OPS/HDM/CD/425-06, Montevideo, Uruguay.

  3. Howard, E. J., Xiong, X., Carlier, Y., Sosa-Estani, S., & Buekens, P. (2014). Frequency of the congenital transmission of Trypanosoma cruzi: A systematic review and meta-analysis. BJOG, 121(1), 22–33.

    Article  CAS  PubMed  Google Scholar 

  4. Freilij, H., & Altchech, J. (1995). Congenital Chagas disease: Diagnostic and clinical aspects. Clinical Infectious Diseases, 21, 551–555.

    Article  CAS  PubMed  Google Scholar 

  5. Sánchez Negrette, O., Mora, M. C., & Basombrío, M. A. (2005). High prevalence of congenital Trypanosoma cruzi infection and family clustering in Salta, Argentina. Pediatrics, 115(6), e668–e672.

    Article  PubMed  Google Scholar 

  6. Torrico, F., Alonso-Vega, C., Suarez, E., Rodriguez, P., et al. (2004). Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia. American Journal of Tropical Medicine and Hygeine, 70(2), 201–209.

    Google Scholar 

  7. Bern, C., Martin, D. L., & Gilman, R. H. (2011). Acute and congenital Chagas disease. Advances in Parasitology, 75, 19–47.

    Article  PubMed  Google Scholar 

  8. Coura, J. R., & Borges-Pereira, J. (2010). Chagas disease: 100 years after its discovery. A systemic review. Acta Tropica, 115(1–2), 5–13.

    Article  PubMed  Google Scholar 

  9. Cunha-Neto, E., Teixeira, P. C., Nogueira, L. G., & Kalil, J. (2011). Autoimmunity. Advances in Parasitology, 76, 129–152.

    Article  PubMed  Google Scholar 

  10. Cunha-Neto, E., Coelho, V., Guilherme, L., Fiorelli, A., Stolf, N., & Kalil, J. (1996). Autoimmunity in Chagas’ disease. Identification of cardiac myosin-B13 Trypanosoma cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas’ cardiomyopathy patient. Journal of Clinical Investigation, 98(8), 1709–1712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Abel, L. C., & Kalil, J. (1997). Cunha Neto E. Molecular mimicry between cardiac myosin and Trypanosoma cruzi antigen B13: Identification of a B13-driven human T cell clone that recognizes cardiac myosin. Brazilian Journal of Medical and Biological Research, 30(11), 1305–1308.

    Article  CAS  PubMed  Google Scholar 

  12. Vicco, M. H., Ferini, F., Rodeles, L., et al. (2013). Assessment of cross-reactive host-pathogen antibodies in patients with different stages of chronic chagas disease. Revista Espanola de Cardiologia, 66(10), 791–796.

    Article  PubMed  Google Scholar 

  13. Vicco, M. H., Pujato, N., Bontempi, I., Rodeles, L., Marcipar, I., & Bottasso, O. (2014). Increased levels of anti-p2β antibodies and decreased cardiac involvement in patients with progressive chronic Chagas heart disease undergoing β1 selective antagonist treatment. Canadian Journal of Cardiology, 30(3), 332–337.

    Article  PubMed  Google Scholar 

  14. Cremaschi, G., Fernandez, M., Gorelik, G., et al. (2004). Modulatory effects on myocardial physiology induced by an anti- monoclonal antibody involve recognition of major antigenic epitopes from β-adrenergic and M-muscarinic cholinergic receptors without requiring receptor cross-linking. Journal of Neuroimmunology, 153(1–2), 99–107.

    Article  CAS  PubMed  Google Scholar 

  15. Joensen, L., Borda, E., Kohout, T., Perry, S., García, G., & Sterin-Borda, L. (2003). Trypanosoma cruzi antigen that interacts with the β1-adrenergic receptor and modifies myocardial contractile activity. Molecular and Biochemical Parasitology, 127(2), 169–177.

    Article  CAS  PubMed  Google Scholar 

  16. Labovsky, V., Smulski, C. R., Gómez, K., Levy, G., & Levin, M. J. (2007). Anti-beta1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease. Clinical and Experimental Immunology, 148(3), 440–449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Levy, G. V., Tasso, L. M., Longhi, S. A., et al. (2011). Antibodies against the Trypanosoma cruzi ribosomal P proteins induce apoptosis in HL-1 cardiac cells. International Journal for Parasitology, 41(6), 635–644.

    Article  CAS  PubMed  Google Scholar 

  18. Robinson, D. P., & Klein, S. L. (2012). Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Hormones and Behavior, 62(3), 263–271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wegmann, T. G., Lin, H., Guilbert, L., & Mosmann, T. R. (1993). Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon? Immunology Today, 14(7), 353–356.

    Article  CAS  PubMed  Google Scholar 

  20. Straub, R. H. (2007). The complex role of estrogens in inflammation. Endocrine Reviews, 28(5), 521–574.

    Article  CAS  PubMed  Google Scholar 

  21. Soldan, S. S., Alvarez Retuerto, A. I., Sicotte, N. L., & Voskuhl, R. R. (2003). Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol. The Journal of Immunology, 171, 6267–6274.

    Article  CAS  PubMed  Google Scholar 

  22. Palmeira, P., Quinello, C., Silveira-Lessa, A. L., Zago, C. A., & Carneiro-Sampaio, M. (2012). IgG placental transfer in healthy and pathological pregnancies. Clinical and Developmental Immunology, 2012, 985646.

    Article  PubMed  Google Scholar 

  23. Kobayashi, R., Mii, S., Nakano, T., Harada, H., & Eto, H. (2009). Neonatal lupus erythematosus in Japan: A review of the literature. Autoimmunity Reviews, 8(6), 462–466.

    Article  PubMed  Google Scholar 

  24. Aznar, C., Lopez-Bergami, P., Brandariz, S., et al. (1995). Prevalence of anti-R-13 antibodies in human Trypanosoma cruzi infection. FEMS Immunology and Medical Microbiology, 12(3–4), 231–238.

    Article  CAS  PubMed  Google Scholar 

  25. Institute of Medicine (US). (2007). Committee on understanding premature birth and assuring healthy outcomes. Measurement of fetal and infant maturity. In R. E. Behrman, A. S. Butler (Eds.), Preterm birth: Causes, consequences, and prevention.

  26. Marcipar, S., Lagier, C. Advances in serological diagnosis of chagas’ disease by using recombinant proteins. In: A Rodriguez-Morales (Ed.), Current topics in tropical medicine. ISBN: 978-953-51-0274-8, InTech. Available from http://www.intechopen.com/books/current-topics-in-tropicalmedicine/advances-in-serological-diagnosis-of-chagas-disease-by-using-recombinant-proteins.

  27. Freilij, H., & Altcheh, J. (1995). Congenital Chagas’ disease: Diagnostic and clinical aspects. Clinical Infectious Diseases, 21(3), 551–555.

    Article  CAS  PubMed  Google Scholar 

  28. Mora, M. C., Sanchez Negrette, O., Marco, D., et al. (2005). Early diagnosis of congenital Trypanosoma cruzi infection using PCR, hemoculture, and capillary concentration, as compared with delayed serology. Journal of Parasitology, 91(6), 1468–1473.

    Article  PubMed  Google Scholar 

  29. Virreira, M., Torrico, F., Truyens, C., et al. (2003). Comparison of polymerase chain reaction methods for reliable and easy detection of congenital Trypanosoma cruzi infection. American Journal of Tropical Medicine and Hygeine, 68, 574–582.

    CAS  Google Scholar 

  30. Carlier, Y., Torrico, F., Sosa-Estani, S., et al. (2011). Congenital Chagas disease: Recommendations for diagnosis, treatment and control of newborns, siblings and pregnant women. PLoS Neglected Tropical Disease, 5(10), e1250. doi:10.1371/journal.pntd.0001250.

    Article  Google Scholar 

  31. Buekens, P., Cafferata, M. L., Alger, J., et al. (2013). Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: Study protocol. Reproductive Health, 11(10), 55. doi:10.1186/1742-4755-10-55.

    Article  Google Scholar 

  32. Bua, J., Volta, B. J., Perrone, A. E., et al. (2013). How to improve the early diagnosis of Trypanosoma cruzi infection: Relationship between validated conventional diagnosis and quantitative DNA amplification in congenitally infected children. PLoS Neglected Tropical Disease, 7(10), e2476. doi:10.1371/journal.pntd.0002476.

    Article  Google Scholar 

  33. Oliveira, I., Torrico, F., Mũnoz, J., & Gascon, J. (2010). Congenital transmission of Chagas disease: A clinical approach. Expert Review Anti-Infect Therapy, 8, 945–956.

    Article  Google Scholar 

  34. Carlier, Y., Truyens, C., Deloron, P., & Peyron, F. (2012). Congenital parasitic infections: A review. Acta Tropica, 121(2), 55–70.

    Article  PubMed  Google Scholar 

  35. Vicco, M. H., Bontempi, I. A., Rodeles, L., Yodice, A., Marcipar, I. S., & Bottasso, O. (2014). Decreased level of antibodies and cardiac involvement in patients with chronic Chagas heart disease vaccinated with BCG. Medical Microbiology and Immunology, 203(2), 133–139.

    Article  CAS  PubMed  Google Scholar 

  36. Marcipar, I. S., Roodveldt, C., Corradi, G., et al. (2005). Use of full-length recombinant calflagin and its c fragment for improvement of diagnosis of Trypanosoma cruzi infection. Journal of Clinical Microbiology, 43(11), 5498–5503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Camussone, C., Gonzalez, V., Belluzo, M. S., et al. (2009). Comparison of recombinant Trypanosoma cruzi peptide mixtures versus multiepitope chimeric proteins as sensitizing antigens for immunodiagnosis. Clinical and Vaccine Immunology, 16(6), 899–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tijssen, P. (1985). Processing of data and reporting of results of enzymeimmunoassays. In: Practice and theory of enzimeimmunoassays. Laboratory techniques in biochemistry and molecular biology (Vol. 15, pp. 385–421). Amsterdam: Elsevier.

  39. Wright, P. F., Nilsson, E., Van Rooij, E. M., Lelenta, M., & Jeggo, M. H. (1993). Standardisation and validation of enzyme-linked immunosorbent assay techniques for the detection of antibody in infectious disease diagnosis. Revue Scientifique et Technique, 12(2), 435–450.

    Article  CAS  PubMed  Google Scholar 

  40. Wahrenberg, H., Arner, P., Engfeldt, P., Haglund, K., Rössner, S., & Ostman, J. (1985). Long-term beta 1-selective adrenergic blockade and adrenergic receptors in human subcutaneous adipocytes. Acta Medica Scandinavica, 217(5), 539–546.

    Article  CAS  PubMed  Google Scholar 

  41. Hoffstedt, J., Arner, P., Hellers, G., & Lönnqvist, F. (1997). Variation in adrenergic regulation of lipolysis between omental and subcutaneous adipocytes from obese and non-obese men. Journal of Lipid Research, 38(4), 795–804.

    CAS  PubMed  Google Scholar 

  42. Langin, D. (2006). Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacological Research, 53(6), 482–491.

    Article  CAS  PubMed  Google Scholar 

  43. Jaworski, K., Sarkadi-Nagy, E., Duncan, R. E., Ahmadian, M., & Sul, H. S. (2007). Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue. American Journal of Physiology. Gastrointestinal and Liver Physiology, 293(1), G1–G4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Blaak, E. E., Van Baak, M. A., Kemerink, G. J., Pakbiers, M. T., Heidendal, G. A., & Saris, W. H. (1994). Beta-Adrenergic stimulation of skeletal muscle metabolism in relation to weight reduction in obese men. American Journal of Physiology, 267(2 Pt 1), E316–E322.

    CAS  PubMed  Google Scholar 

  45. Jocken, J. W., Goossens, G. H., van Hees, A. M., et al. (2008). Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men. Diabetologia, 51(2), 320–327.

    Article  CAS  PubMed  Google Scholar 

  46. Gürtler, R. E., Segura, E. L., & Cohen, J. E. (2003). Congenital transmission of Trypanosoma cruzi infection in Argentina. Emerging Infectious Diseases, 9(1), 29–32.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Fretes, R. E., & Kemmerling, U. (2012). Mechanism of Trypanosoma cruzi placenta invasion and infection: The use of human chorionic villi explants. Journal of Tropical Medicine, 2012, 614820.

    PubMed  PubMed Central  Google Scholar 

  48. Saji, F., Koyama, M., & Matsuzaki, N. (1994). Current topic: Human placental Fc receptors. Placenta, 15(5), 453–466.

    Article  CAS  PubMed  Google Scholar 

  49. Vicco, M. H., Rodeles, L., Yódice, A., Marcipar, I. (2014). Chagas disease, a risk factor for high blood pressure. Blood Pressure. [Epub ahead of print].

  50. Johnson, J. A., & Liggett, S. B. (2011). Cardiovascular pharmacogenomics of adrenergic receptor signaling: Clinical implications and future directions. Clinical Pharmacology and Therapeutics, 89(3), 366–378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Nguyen, G., Delarue, F., Burcklé, C., Bouzhir, L., Giller, T., & Sraer, J. D. (2002). Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. JCI, 109, 1417–1427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Suzuki, Y., Ruiz-Ortega, M., Lorenzo, O., Ruperez, M., Esteban, V., & Egido, J. (2003). Inflammation and angiotensin II. International Journal of Biochemistry & Cell Biology, 35(6), 881–900.

    Article  CAS  Google Scholar 

  53. Chen, C., Du, J., Feng, W., Song, Y., Lu, Z., Xu, M., et al. (2012). β-Adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCδ/p38 MAPK signalling in neonatal mouse cardiac fibroblasts. British Journal of Pharmacology, 166(2), 676–688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lockwood, C. J., Yen, C. F., Basar, M., Kayisli, U. A., Martel, M., Buhimschi, I., et al. (2008). Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells. American Journal of Pathology, 172(6), 1571–1579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sharma, A. M., Pischon, T., Hardt, S., Kunz, I., & Luft, F. C. (2001). Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic analysis. Hypertension, 37(2), 250–254.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

M.H.V L.R and M. P are research fellows of the National Scientific and Technical Research Council (CONICET). I.S.M and O.B. are research career members of CONICET. This work was in part supported by the “Institut de Recherche pour le Développement (IRD) through its program of “JeunesEquipesAssociées à l´IRD”.

Author information

Author notes

    Authors and Affiliations

    1. Laboratorio de Tecnología Inmunológica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, CC242, 3000, Santa Fe, Argentina

      Miguel Hernán Vicco, Luz Rodeles, Melina Perrig & Iván Marcipar

    2. Facultad de Ciencias Médicas, Universidad Nacional del Litoral, Santa Fe, Argentina

      Miguel Hernán Vicco, Luz Rodeles & Gabriela Soledad Capovilla

    3. Unidad de Inmunología Parasitaria, Facultad de Medicina, Universidad Mayor de San Andrés, La Paz, Bolivia

      Ana Gabriela Herrera Choque, Celeste Rodriguez & Washington Cuña

    4. Instituto de Inmunología Clínica y Experimental de Rosario, CONICET-UNR, Rosario, Argentina

      Oscar Bottasso

    Authors
    1. Miguel Hernán Vicco
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Luz Rodeles
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Gabriela Soledad Capovilla
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Melina Perrig
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Ana Gabriela Herrera Choque
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Iván Marcipar
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Oscar Bottasso
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Celeste Rodriguez
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Washington Cuña
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Miguel Hernán Vicco.

    Ethics declarations

    Conflict of interest

    There was no conflicts of interests.

    Additional information

    Miguel Hernán Vicco and Luz Rodeles have contributed equally to this study.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Vicco, M.H., Rodeles, L., Capovilla, G.S. et al. IgG Autoantibodies Induced by T. cruzi During Pregnancy: Correlation with Gravidity Complications and Early Outcome Assessment of the Newborns. Matern Child Health J 20, 2057–2064 (2016). https://doi.org/10.1007/s10995-016-2035-8

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10995-016-2035-8

    Keywords

    Search

    Navigation