Schistosome Infection Intensity is Inversely Related to Auto-reactive Antibody Levels

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 May 17

PMID 21573157

Citations 21

Authors

Francisca Mutapi

Natsuko Imai

Norman Nausch

Claire D Bourke

Nadine Rujeni

Kate M Mitchell

Nicholas Midzi

Mark E J Woolhouse

Rick M Maizels

Takafira Mduluza

Affiliations

Soon will be listed here.

Abstract

In animal experimental models, parasitic helminth infections can protect the host from auto-immune diseases. We conducted a population-scale human study investigating the relationship between helminth parasitism and auto-reactive antibodies and the subsequent effect of anti-helminthic treatment on this relationship. Levels of antinuclear antibodies (ANA) and plasma IL-10 were measured by enzyme linked immunosorbent assay in 613 Zimbabweans (aged 2-86 years) naturally exposed to the blood fluke Schistosoma haematobium. ANA levels were related to schistosome infection intensity and systemic IL-10 levels. All participants were offered treatment with the anti-helminthic drug praziquantel and 102 treated schoolchildren (5-16 years) were followed up 6 months post-antihelminthic treatment. ANA levels were inversely associated with current infection intensity but were independent of host age, sex and HIV status. Furthermore, after allowing for the confounding effects of schistosome infection intensity, ANA levels were inversely associated with systemic levels of IL-10. ANA levels increased significantly 6 months after anti-helminthic treatment. Our study shows that ANA levels are attenuated in helminth-infected humans and that anti-helminthic treatment of helminth-infected people can significantly increase ANA levels. The implications of these findings are relevant for understanding both the aetiology of immune disorders mediated by auto-reactive antibodies and in predicting the long-term consequences of large-scale schistosomiasis control programs.

Citing Articles

Herpes simplex virus type 2 in sub-Saharan Africa and the potential impact of helminth immune modulation.

Pillay R, Naidoo P, Mkhize-Kwitshana Z Front Cell Infect Microbiol. 2024; 14():1471411.

PMID: 39698320 PMC: 11652539. DOI: 10.3389/fcimb.2024.1471411.

Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review.

Mertelsmann A, Bowers S, Wright D, Maganga J, Mazigo H, Ndhlovu L PLoS Negl Trop Dis. 2024; 18(9):e0012456.

PMID: 39250522 PMC: 11412685. DOI: 10.1371/journal.pntd.0012456.

Regulatory T-cells in helminth infection: induction, function and therapeutic potential.

White M, McManus C, Maizels R Immunology. 2020; 160(3):248-260.

PMID: 32153025 PMC: 7341546. DOI: 10.1111/imm.13190.

Placental gene expression and antibody levels of mother-neonate pairs reveal an enhanced risk for inflammation in a helminth endemic country.

Ludwig E, Harder J, Lacorcia M, Josiane Honkpehedji Y, Nouatin O, van Dam G Sci Rep. 2019; 9(1):15776.

PMID: 31673046 PMC: 6823435. DOI: 10.1038/s41598-019-52074-z.

Cross-Domain and Viral Interactions in the Microbiome.

Rowan-Nash A, Korry B, Mylonakis E, Belenky P Microbiol Mol Biol Rev. 2019; 83(1).

PMID: 30626617 PMC: 6383444. DOI: 10.1128/MMBR.00044-18.

References

Mutapi F, Burchmore R, Mduluza T, Foucher A, Harcus Y, Nicoll G . Praziquantel treatment of individuals exposed to Schistosoma haematobium enhances serological recognition of defined parasite antigens. J Infect Dis. 2005; 192(6):1108-18. DOI: 10.1086/432553. View

van den Biggelaar A, Van Ree R, Rodrigues L, Lell B, Deelder A, Kremsner P . Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet. 2000; 356(9243):1723-7. DOI: 10.1016/S0140-6736(00)03206-2. View

Cooper P, Chico M, Rodrigues L, Ordonez M, Strachan D, Griffin G . Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol. 2003; 111(5):995-1000. DOI: 10.1067/mai.2003.1348. View

La Flamme A, Ruddenklau K, Backstrom B . Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun. 2003; 71(9):4996-5004. PMC: 187318. DOI: 10.1128/IAI.71.9.4996-5004.2003. View

Smith P, Mangan N, Walsh C, Fallon R, McKenzie A, van Rooijen N . Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol. 2007; 178(7):4557-66. DOI: 10.4049/jimmunol.178.7.4557. View

Adu D, Williams D, Quakyi I, Voller A, JOHNSON G, HOLBOROW E . Anti-ssDNA and antinuclear antibodies in human malaria. Clin Exp Immunol. 1982; 49(2):310-6. PMC: 1536512. View

Woolhouse M . Patterns in parasite epidemiology: the peak shift. Parasitol Today. 2006; 14(10):428-34. DOI: 10.1016/s0169-4758(98)01318-0. View

Mabaso M, Vounatsou P, Midzi S, da Silva J, Smith T . Spatio-temporal analysis of the role of climate in inter-annual variation of malaria incidence in Zimbabwe. Int J Health Geogr. 2006; 5:20. PMC: 1513195. DOI: 10.1186/1476-072X-5-20. View

Lleo A, Invernizzi P, Gao B, Podda M, Gershwin M . Definition of human autoimmunity--autoantibodies versus autoimmune disease. Autoimmun Rev. 2009; 9(5):A259-66. DOI: 10.1016/j.autrev.2009.12.002. View

10.

Joseph S, Jones F, Walter K, Fulford A, Kimani G, Mwatha J . Increases in human T helper 2 cytokine responses to Schistosoma mansoni worm and worm-tegument antigens are induced by treatment with praziquantel. J Infect Dis. 2004; 190(4):835-42. DOI: 10.1086/422604. View

11.

Milner T, Reilly L, Nausch N, Midzi N, Mduluza T, Maizels R . Circulating cytokine levels and antibody responses to human Schistosoma haematobium: IL-5 and IL-10 levels depend upon age and infection status. Parasite Immunol. 2010; 32(11-12):710-21. PMC: 3033519. DOI: 10.1111/j.1365-3024.2010.01235.x. View

12.

Taylor P, Mutambu S . A review of the malaria situation in Zimbabwe with special reference to the period 1972-1981. Trans R Soc Trop Med Hyg. 1986; 80(1):12-9. DOI: 10.1016/0035-9203(86)90185-9. View

13.

Liu Z, Liu Q, Bleich D, Salgame P, Gause W . Regulation of type 1 diabetes, tuberculosis, and asthma by parasites. J Mol Med (Berl). 2009; 88(1):27-38. PMC: 2863045. DOI: 10.1007/s00109-009-0546-0. View

14.

Mingomataj E, Xhixha F, Gjata E . Helminths can protect themselves against rejection inhibiting hostile respiratory allergy symptoms. Allergy. 2006; 61(4):400-6. DOI: 10.1111/j.1398-9995.2006.00983.x. View

15.

Daniel-Ribeiro C, Zanini G . Autoimmunity and malaria: what are they doing together?. Acta Trop. 2000; 76(3):205-21. DOI: 10.1016/s0001-706x(00)00099-1. View

16.

Cooke A, Tonks P, Jones F, OShea H, Hutchings P, Fulford A . Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 1999; 21(4):169-76. DOI: 10.1046/j.1365-3024.1999.00213.x. View

17.

Mott K . A reusable polyamide filter for diagnosis of S. haematobium infection by urine filtration. Bull Soc Pathol Exot Filiales. 1983; 76(1):101-4. View

18.

Katz N, Chaves A, Pellegrino J . A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo. 1972; 14(6):397-400. View

19.

Endara P, Vaca M, Chico M, Erazo S, Oviedo G, Quinzo I . Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity. Clin Exp Allergy. 2010; 40(11):1669-77. PMC: 3034193. DOI: 10.1111/j.1365-2222.2010.03559.x. View

20.

Maizels R, Pearce E, Artis D, Yazdanbakhsh M, Wynn T . Regulation of pathogenesis and immunity in helminth infections. J Exp Med. 2009; 206(10):2059-66. PMC: 2757871. DOI: 10.1084/jem.20091903. View