Skip to main content
NCBI home page
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2000 Jan 24;14(1):5–12. doi: 10.1002/(SICI)1098-2825(2000)14:1<5::AID-JCLA2>3.0.CO;2-F

Detection of specific antibody isotypes and subtypes before and after treatment of American visceral leishmaniasis

Vânia LR da Matta 1,✉, Sumie Hoshino‐Shimizu 2, Reynaldo Dietze 3, Carlos EP Corbett 1
PMCID: PMC6807925  PMID: 10645978

Abstract

Sera from patients with American visceral leishmaniasis (AVL) were studied before and after treatment based on their antibody isotypes and subtypes. The study was comprised of 33 Brazilian patients with well‐defined diagnosis of AVL and 39 clinically healthy individuals. Antileishmanial antibody isotypes and subtypes were observed in almost all patients, except IgA that was detected in about 63% of them. The sensitivity and specificity of the immunofluorescence assay in the detection of antibody isotypes (IgG and IgM) and subtypes (IgG1, IgG2, IgG3, and IgG4) were high with no statistical difference, ranging from 0.937 to 1.000 and from 0.954 to 1.000, respectively. All IgG antibodies and its subtypes had their levels reduced after treatment. However, the IgG4 had an early decay and its conversion to negative was significantly high in children. Moreover, the profile of IgG4 before treatment corresponded to a unimodal curve that shifted to a patent bimodal curve after treatment, indicative of therapeutic success. Thus, the IgG4 shows to be a suitable immunological marker for the assessment of chemotherapy in AVL patients or communities. Our findings suggest that IgG4 correlates with IL‐4 that also decreases after therapy. J. Clin. Lab. Anal. 14:5–12, 2000. © 2000 Wiley‐Liss, Inc.

Keywords: IgG classes, IgG subclasses, IgM, IgA, immunofluorescence technique, follow‐up studies, serodiagnosis, serology, serological profiles, immunological markers

REFERENCES

  • 1. Evans TG, Teixeira MJ, McAuliffe IT, et al. Epidemiology of visceral leishmaniasis in northeast Brazil. J Infect Dis 1992;46:1124–1132. [DOI] [PubMed] [Google Scholar]
  • 2. Rey L. Leishmaniose ou Calazar In: Bases da parasitologia médica. Rio de Janeiro, Brazil: Guanabara Koogan SA, 1992, p 58–65. [Google Scholar]
  • 3. Zwingenberger K, Harms G, Pedrosa C, Omena S, Sandkamp B, Neifer S. Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon gamma production. Clin Immunol Immunopath 1990;57:242–249. [DOI] [PubMed] [Google Scholar]
  • 4. Sundar S, Reed SG, Sharma S, Mehrotra A, Murray HW. Circulating T helper 1 (Th1) cell and Th2 cell‐associated cytokines in Indian patients with visceral leishmaniasis. Am J Trop Med Hyg 1997;56(5):522–525. [DOI] [PubMed] [Google Scholar]
  • 5. Murray HW, Rubin BY, Rothermel CD. Killing of intracellular Leishmania donovani by lymphokine‐stimulated human mononuclear phagocytes. Evidence that interferon‐γ is the activating lymphokine. J Clin Invest 1983;72:106–110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Carvalho EM, Bacellar O, Brownell C, Regis T, Coffman RL, Reed SG. Restoration of IFN‐g production and lymphocyte proliferation in visceral leishmaniasis. J Immunol 1994;152:5949–5956. [PubMed] [Google Scholar]
  • 7. Liew F, O'Donnell CA. Immunology of leishmaniasis. Adv Parasitol 1993;32 162–222. [DOI] [PubMed] [Google Scholar]
  • 8. Badaró R, Reed SG, Carvalho EM. Immunofluorescent antibody test in American visceral leishmaniasis: sensitivity and specificity of different morphological forms of two Leishmania species. Am J Trop Med Hyg 1983;32:480–484. [DOI] [PubMed] [Google Scholar]
  • 9. Mary C, Lamouroux D, Dunan S, Quilici M. Western blot analysis of antibodies to Leishmania infantum antigens: potential of the 14‐KD and 16‐KD antigens for diagnosis and epidemiologic purposes. Am J Trop Med Hyg 1992;47(6):764–771. [DOI] [PubMed] [Google Scholar]
  • 10. Schaefer KU, Kurtzhals JA, Gachihi GS, Muller AS, Kager PA. A prospective sero‐epidemiological study of visceral leishmaniasis in Baringo District, Rift Valley Province, Kenya. Trans R Soc Trop Med Hyg 1995;89(5):471–475. [DOI] [PubMed] [Google Scholar]
  • 11. Shiddo SA, Mohamed AA, Huldt G, et al. Visceral leishmaniasis in Somalia. Circulating antibodies as measured by DAT, immunofluorescence and ELISA. Trop Geogr Med 1995;47(2):69–73. [PubMed] [Google Scholar]
  • 12. Neogy AB, Nandy A, Ghosh Dastidar B, Chowdhury AB. Antibody kinetics in kala‐azar in response to treatment. Ann Trop Med Parasitol 1987;81:727–729. [DOI] [PubMed] [Google Scholar]
  • 13. Edrissian Par Gh H, Hafizi A, Afshar A, Soleiman‐Zadeh Gh, Movahed‐Danesh AM, Garoussi A. An endemic focus of visceral leishmaniasis in Meshkin‐Shahr, East Azerbaijan province, north‐west part of Ira and IFA serological survey of the disease in this area. Bull Soc Path Ex 1988;81:238–248. [PubMed] [Google Scholar]
  • 14. Hailu A. Pre‐ and post‐treatment antibody levels in visceral leishmaniasis. Trans R Soc Trop Med Hyg 1990;84:673–675. [DOI] [PubMed] [Google Scholar]
  • 15. Okong'o‐Odera EA, Kurtzhals JAL, Hey AS, Kharazmi. Measurement of serum antibodies against native Leishmania gp63 distinguishes between ongoing and previous L. donovani infection. APMIS 1993;101:642–646. [DOI] [PubMed] [Google Scholar]
  • 16. Cardeñosa N, Riera C, Cortés P, March F, Muñoz C, Portús M, Prats G. Detection and characterization by immunoblot analysis of potentially diagnostic Leishmania infantum polypeptides in human visceral leishmaniasis. Parasite Immunol 1995;17:509–516. [DOI] [PubMed] [Google Scholar]
  • 17. Palatinik‐de‐Sousa CB, Gomes EM, Paraguai‐de‐Souza E, Palatinik M, Luz K, Borojevic R. Leishmania donovani: titration of antibodies to the fucose‐mannose ligand as an aid in diagnosis and prognosis of visceral leishmaniasis. Trans R Soc Trop Med Hyg 1995;89(4):390–393. [DOI] [PubMed] [Google Scholar]
  • 18. El Amin EM, Wright EP, VLug A. Characterization of the humoral immune response in Sudanese leishmaniasis: specific antibody detected by class and subclass‐specific reagents. Clin Exp Immunol 1986;64:14–19. [PMC free article] [PubMed] [Google Scholar]
  • 19. Elassad AMS, Younis SA, Siddig M, Grayson J, Petersen E, Ghalib HW. The significance of blood levels of IgM, IgA, IgG and IgG subclasses in Sudanese visceral leishmaniasis patients. Clin Exp Immunol 1994;95:294–299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Gosh AK, Dasgupta S, Ghose AC. Immunoglobulin G subclass‐specific antileishmanial antibody responses in Indian kala‐azar and post‐kala‐azar dermal leishmaniasis. Clin Diagn Lab Immunol 1995;2(3):291–296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Ulrich M, Rodriguez V, Centeno M, Convit J. Differing antibody isotypes in the polar forms of leprosy and cutaneous leishmaniasis characterized by antigen‐specific T cell anergy. Clin Exp Immunol 1995;100:54–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Atta AM, D'Oliveira A Jr, Correa J, Atta MLB, Almeida RP, Carvalho EM. Anti‐ leishmanial IgE antibodies: a marker of active disease in visceral leishmaniasis. Am J Trop Med Hyg 1998;59(3):426–430. [DOI] [PubMed] [Google Scholar]
  • 23. Badaró R, Reed SG, Barral A, Orge G, Jones TC. Evaluation of micro enzyme‐linked immunosorbent assay (ELISA) for antibodies in American visceral leishmaniasis: antigen selection for detection of infection‐specific responses. Am J Trop Med Hyg 1986;35:72–78. [DOI] [PubMed] [Google Scholar]
  • 24. Kanamura HY, Hoshino‐Shimizu S, Kimura RT, Matsumoto TK, Silva LC, Lima DMC, Abrantes‐Lemos CP. Decay of antibody isotypes against developmental stages of Schistosoma mansoni after treatment of schistosomiasis patients. Rev Inst Med Trop São Paulo 1997;39:137–140. [DOI] [PubMed] [Google Scholar]
  • 25. Ghose AC, Haldar JP, Pal SC, Mishra BP, Mishra KK. Serological investigations on Indian kala‐azar. Clin Exp Immunol 1980;40:318–326. [PMC free article] [PubMed] [Google Scholar]
  • 26. Kanamura HY, Hoshino‐Shimizu S, Silva LC. Schistosoma mansoni cercariae and schistosomulum antigens in serological tests for the diagnosis of schistosomiasis. Bull Pan Amer Health Org 1992;26:220–229. [PubMed] [Google Scholar]
  • 27. Guimarães MCS, Ferreira AW, Carvalho MB, Celeste BJ, e LC, Belda W Jr.. Anti‐Leishmania IgA immunoenzymatic assay in mucocutaneous leishmaniasis. Rev Inst Med Trop São Paulo 1984;26:353–356. [DOI] [PubMed] [Google Scholar]
  • 28. O'Neil CE, Labrada M, Saravia NG. Leishmania (Viannia) panamensis‐specific IgE and IgA antibodies in relation to expression of human tegumentary leishmaniasis. Am J Trop Med Hyg 1993;49(2):181–188. [DOI] [PubMed] [Google Scholar]
  • 29. Primavera KSC, Hoshino‐Shimizu S, Umezawa ES, Peres BA, Manigot DA, Camargo ME. Immunoglobulin A antibodies to Trypanosoma cruzi antigens in digestive forms of Chagas'disease. J Clin Microbiol 1988;26:1201–1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Montella F, Pezzotti P, Di Sora F, Recchia O, Lauria F, Rezza G. Improving the prognostic value of CD4+ count using IgA and clinical signs in HIV‐seropositive i.v. drug users. Infection 1997;25:117–120. [DOI] [PubMed] [Google Scholar]
  • 31. Martin SK, Thuitta‐Harun L, Adoyo‐Adoyo M, Wassuna KM. A diagnostic ELISA for visceral leishmaniasis based on antigen from media conditioned by Leishmania donovani promastigotes. Ann Trop Med Parasitol 1998;92(5):571–577. [DOI] [PubMed] [Google Scholar]
  • 32. Sundar S, Redd SG, Singh VP, Kumar PC, Murray HW. Rapid accurate field diagnosis of Indian visceral leishmaniasis. Lancet 1998;351(9102):563–565. [DOI] [PubMed] [Google Scholar]
  • 33. Ghalib HW, Piuvezam MR, Skeiky YA, et al. Interleukin 10 production correlates with pathology in human Leishmania donovani infections. J Clin Invest 1993;92:324–329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Karp CL, El‐Safi SH, Wynn TA, et al. In vivo cytokine profiles in patients with kala‐azar. Marked elevation of both interleukin‐10 and interferon‐gamma. J Clin Invest 1993;91:1644–1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Kawano Y, Noma T, Yata. Regulation of human IgG subclass production by cytokines. IFN‐gamma and IL‐6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2. J Immunol 1994;153(11):4948–4958. [PubMed] [Google Scholar]
  • 36. Deplazes P, Smith NC, Arnold P, Lutz H, Eckert J. Specific IgG1 and IgG2 antibody responses of dogshmanias to Leishmania infantum and other parasites. Parasite Immunol 1995;17(9):451–458. [DOI] [PubMed] [Google Scholar]
  • 37. Ishizaka A, Sakiyama Y, Nakanishi K, et al. The inductive effect of interleukin‐4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes. Clin Exp Immunol 1990;79:392–396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Gascan H, Gauchat JF, Roncarolo MG, Yssel H, Spits H, de Vries JE. Human B cells clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J Exp Med 1991;173(3):747–750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Brière F, Servet‐Delprat C, Bridon JM, Saint‐Remy JM, Banchereau J. Human interleukin 10 induces naive surface immunoglobulin D+ (sIgD+) B cells to secrete IgG1 and IgG3. J Exp Med 1994;179:757–772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Siber GR, Schur PH, Aisenberg AC, Weitzman SA, Schiffman G. Correlation between serum IgG2 concentrations and the antibody response to bacterial polysaccharide antigens. N Engl J Med 1980;303:178–180. [DOI] [PubMed] [Google Scholar]
  • 41. Burns JM, Shreffler WG, Benson DR, Ghalib HW, Badaró R, Reed SG. Molecular characterization of a kinesin‐related antigen of Leishmania chagasi that detects specific antibody in African and American visceral leishmaniasis. Proc Natl Acad Sci U S A 1993;90:775–779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Shreffler WG, Burns JM, Badaró R, et al. The antibody responses of visceral leishmaniasis patients to gp63, a recombinant major surface glycoprotein on Leishmania species. J Infect Dis 1993;167:426–430. [DOI] [PubMed] [Google Scholar]
  • 43. Jeanin P, Delnest Y, Tellie‐ Leblond I, et al. Abnormal IgG4 antibody response in aeroallergens in allergic patients. Int Arch Allergy Immunol 1994;104:191–198. [DOI] [PubMed] [Google Scholar]
  • 44. Webster M, Libranda‐Ramirez BDL, Aligui GD, et al. The influence of sex and age on antibody isotype responses to Schistosoma mansoni and Schistosoma japonicum in human populations in Kenya and Philippines. Parasitol 1997;114:383–393. [DOI] [PubMed] [Google Scholar]
  • 45. Duarte MIS, Mariano ON, Corbett CEP. Liver parenchymal cell parasitism in human visceral leishmaniasis. Virch Arch Pathol Anat 1989;415:1–6. [DOI] [PubMed] [Google Scholar]
  • 46. Nicodemo EL, Duarte MIS, Corbett CEP, et al. Visceral leishmaniasis in AIDS patient. Rev Med Trop São Paulo 1990;32(4):310–311. [DOI] [PubMed] [Google Scholar]
  • 47. Estamble BB, Knight R. Protozoan infections and HIV‐1 infection: a review. East Afr Med J 1992;69:373–377. [PubMed] [Google Scholar]
  • 48. Berhe N, Hailu A, Wolday D, Negesse Y, Cenini P, Frommel D. Ethiopian visceral leishmaniasis patients co‐infected with human immunodeficiency virus. Trans R Trop Med Hyg 1995;89:205–207. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES