Skip to main content

Advertisement

Log in

Purified proteins from leishmania amastigotes-induced delayed type hypersensitivity reactions and remission of collagen-induced arthritis in animal models

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

A treatment preparation composed of purified Leishmania (L) antigenic fractions (AS210) induced linear delayed type hypersensitivity (DTH) reactions over a 1–40 μg dose range, in guinea pigs. When a DBA-1 mouse collagen induced arthritis (CIA) model was used to compare AS210 treatment against: a polyvalent vaccine (AS110-1), a monovalent vaccine (AS110-2) and placebo, the AS210 treated mice had the least amount of forepaw inflammation and the lowest mean arthritis scores (MAS). When MAS for day(s) 1–40 were analyzed using one way ANOVA, statistically significant (P < 0.05) differences were seen for the following study groups: PBS versus Dexamethasone and PBS versus AS210. Subsequently, the ANOVA analysis results were corroborated by the Mann–Whitney test: analysis of the first group (P < 0.001) and analysis of the second group (P < 0.001). Comparison between dexamethasone and AS210 at different time intervals by Mann–Whitney test were as follows: day 0–day 5 both treatments had equal values (P = 1.00), from day-7 to 20 AS210 treatment had lower MAS values than dexamethasone (P = 0.037), and from day-21 to 30, AS210 MAS were similar to dexamethasone values (P = 0.319). No statistical difference was observed between AS110-1, AS110-2, and placebo groups.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Borg AA, Nixon NB, Dawes PT et al (1994) Increased IgA antibodies to cytokeratins in the spondyloarthropathies. Ann Rheum Dis 53:391–395

    Article  CAS  PubMed  Google Scholar 

  2. Boyle DL, Kavanaugh A (2008) The pathobiology of psoriatic synovium. Curr Opin Rheumatol 20:404–407

    Article  PubMed  Google Scholar 

  3. Boyman O, Conrad C, Dudli C et al (2005) Activation of dendritic antigen-presenting cells expressing common heat shock protein receptor CD91 during induction of psoriasis. Br J Dermatol 152:1211–1218

    Article  CAS  PubMed  Google Scholar 

  4. Chang X, Jian X, Yan X (2009) Expression and citrullination of keratin in synovial tissue of rheumatoid arthritis. Rheumatol Int 29:1337–1342

    Article  CAS  PubMed  Google Scholar 

  5. Christophers E, Mrowietz U (2003) Psoriasis. In: Freedberg IM, Eisen AZ, Wolff K, Austen FK, Goldsmith LA, Katz SI (eds) Fitzpatrick’s dermatology in general medicine, 6th edn. McGraw-Hill, New York, pp 407–427

    Google Scholar 

  6. Courtenay JS, Dallman MJ, Dayan AD et al (1980) Immunization against heterologous type II collagen induces arthritis in mice. Nature 283:666–668

    Article  CAS  PubMed  Google Scholar 

  7. De Rossell RA, Bray RS, Alexander J (1987) The correlation between delayed hypersensitivity, lymphocyte activation and protective immunity in experimental murine leishmaniasis. Parasite Immunol 9:105–115

    Article  PubMed  Google Scholar 

  8. Dinser R (2008) Animal models for arthritis. Best Pract Res Clin Rheumatol 22:253–267

    Article  CAS  PubMed  Google Scholar 

  9. Falgarone G, Semerano L, Rullé S et al (2009) Targeting lymphocyte activation to treat rheumatoid arthritis. Joint Bone Spine 76:327–332

    Article  CAS  PubMed  Google Scholar 

  10. Fournier C (2005) Where do T cells stand in rheumatoid arthritis? Joint Bone Spine 72:527–532

    Article  PubMed  Google Scholar 

  11. Gabriel SE, Michaud K (2009) Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther 11:229. doi:10.1186/ar2669

    Article  PubMed  Google Scholar 

  12. Goëb V, Thomas-L’Otellier M, Daveau R et al (2009) Candidate autoantigens identified by mass spectrometry in early rheumatoid arthritis are chaperones and citrullinated glycolytic enzymes Arthritis Res Ther. doi:10.1186/ar2644

  13. Hueber AJ, McInnes IB (2007) Immune regulation in psoriasis and psoriatic arthritis recent developments. Immunol Lett 114:59–65

    Article  CAS  PubMed  Google Scholar 

  14. Kemp M, Hansen MB, Theander TG (1992) Recognition of leishmania antigens by T lymphocytes from nonexposed individuals. Infect Immun 60:2246–2251

    CAS  PubMed  Google Scholar 

  15. Klareskog L, Catrina AI, Paget S (2009) Rheumatoid arthritis. Lancet 373:659–672

    Article  CAS  PubMed  Google Scholar 

  16. Klein C, Wustefeld T, Assmus U et al (2005) The IL-6gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury. J Clin Invest 115:860–869

    CAS  PubMed  Google Scholar 

  17. Kochetkova I, Trunkle T, Callis G et al (2008) Vaccination without autoantigen protects against collagen II-induced arthritis via immune deviation and regulatory T cells. J Immunol 181:2741–2752

    CAS  PubMed  Google Scholar 

  18. Li L, Wang H, Wang B (2008) Anergic cells generated by blocking CD28 and CD40 costimulatory pathways in vitro ameliorate collagen induced arthritis. Cell Immunol 254:39–45

    Article  CAS  PubMed  Google Scholar 

  19. Li R, Li X, Li Z (2009) Altered collagen II 263–272 peptide immunization induces inhibition of collagen-induced arthritis through a shift toward Th2-type response. Tissue Antigens 73:341–347

    Article  CAS  PubMed  Google Scholar 

  20. Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  21. Luross JA, Williams NA (2001) The genetic and immunopathological processes underlying collagen-induced arthritis. Immunology 103:407–416

    Article  CAS  PubMed  Google Scholar 

  22. Maciejewska H, Jüngel A, Gay RE et al (2009) Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis. Mol Immunol 47:12–18

    Article  Google Scholar 

  23. Mandik-Nayak L, Ridge N, Fields MJ et al (2008) Role of B cells in systemic lupus erythematosus and rheumatoid arthritis. Curr Opin Immunol 20:639–645

    Article  CAS  PubMed  Google Scholar 

  24. Myers KL, Terato K, Seyer JM et al (1992) Characterization of a tolerogenic T cell epitope of Type II collagen and its relevance to collagen-induced arthritis. J Immunol 149:1439–1443

    CAS  PubMed  Google Scholar 

  25. Nandakumar KS (2010) Pathogenic antibody recognition of cartilage. Cell Tissue Res 339:213–220

    Article  CAS  PubMed  Google Scholar 

  26. Nandakumar KS, Bajtner E, Hill L et al (2008) Arthritogenic antibodies specific for a major type II collagen triple-helical epitope bind and destabilize cartilage independent of inflammation. Arthritis Rheum 58:184–196

    Article  CAS  PubMed  Google Scholar 

  27. Nickdel MB, Conigliaro P, Valesini G et al (2009) Dissecting the contribution of innate and antigen-specific pathways to the breach of self-tolerance observed in a murine model of arthritis. Ann Rheum Dis 68:1059–1066

    Article  CAS  PubMed  Google Scholar 

  28. O’Daly JA, Rodriguez B, Ovalles T et al (2009) Lymphocyte subsets in peripheral blood of patients with psoriasis before and after treatment with leishmania antigens. Arch Dermatol Res. doi:10.1007/s00403-009-0992-0

  29. O’Daly JA, Lezama R, Gleason J (2009) Isolation of Leishmania amastigote protein fractions which induced lymphocyte stimulation and remission of psoriasis. Arch Dermatol Res 301:1–17

    Article  PubMed  Google Scholar 

  30. O’Daly JA, Lezama R, Rodriguez PJ et al (2009) Antigens from Leishmania amastigotes induced clinical remission of psoriasis. Arch Dermatol Res 301:1–13

    Article  PubMed  Google Scholar 

  31. O’Daly JA, Rodríguez MB (1988) Differential growth requirement of several Leishmania spp in chemically defined culture media. Acta Trop 45:109–126

    PubMed  Google Scholar 

  32. O’Daly JA, Cebra JJ (1971) Rabbit secretory IgA III. Chemical and physicochemical studies of its component polypeptide chains. Biochemistry 10:3843–3850

    Article  PubMed  Google Scholar 

  33. O’Daly JA, Serrano L, Rodríguez MB (1983) Free amino-acid pool and proteolytic enzymes in Trypanosoma cruzi, cultured in vitro. Int J Parasitol 13:433–440

    Article  PubMed  Google Scholar 

  34. Passos MA, Barreto SM, Romanha AJ et al (2000) American cutaneous leishmaniasis: use of a skin test as a predictor of relapse after treatment. Bull World Health Organ 78:968–974

    CAS  PubMed  Google Scholar 

  35. Pearson RD et al (1983) The immunobiology of leishmaniasis. Rev Infect Dis 5:907–927

    CAS  PubMed  Google Scholar 

  36. Pratt AG, Isaacs JD, Mattey DL (2009) Current concepts in the pathogenesis of early rheumatoid arthritis. Best Pract Res Clin Rheumatol 23:37–48

    Article  CAS  PubMed  Google Scholar 

  37. Rajesh Rajaiah R, Moudgil KD (2009) Heat-shock proteins can promote as well as regulate autoimmunity. Autoimmun Rev 8:388–393

    Article  PubMed  Google Scholar 

  38. Rambukkana A, Das PK, Witkamp L et al (1993) Antibodies to mycobacterial 65-kDa heat shock protein and other immunodominant antigens in patients with psoriasis. J Invest Dermatol 100:87–92

    Article  CAS  PubMed  Google Scholar 

  39. Rat AC, Boissier MC (2004) Rheumatoid arthritis: direct and indirect costs. Joint Bone Spine 71:518–524

    Article  PubMed  Google Scholar 

  40. Rath A, Glibowicka M, Nadeau VG et al (2009) Detergent binding explains anomalous SDS-PAGE migration of membrane proteins. Proc Natl Acad Sci USA 106:1760–1765

    Article  CAS  PubMed  Google Scholar 

  41. Rooman RPA, Kuijpers G, Gresnigt R et al (2003) Dexamethasone differentially inhibits thyroxine- or growth hormone-induced body and organ growth of snell dwarf mice. Endocrinology 144:2553–2558

    Article  CAS  PubMed  Google Scholar 

  42. Rozenblit M, Lebwohl M (2009) New biologics for psoriasis and psoriatic arthritis. Dermatol Ther 22:56–60

    Article  PubMed  Google Scholar 

  43. Saravia NG, Weigle K, Segura I et al (1990) Recurrent lesions in human leishmania brasiliensis infection: reactivation or reinfection? Lancet 336:398–402

    Article  CAS  PubMed  Google Scholar 

  44. Segawa Y, Itokazu Y, Inoue N et al (2001) Possible changes in expression of chemotaxin LECT2 mRNA in mouse liver after Concanavalin A-induced hepatic injury. Biol Pharm Bull 24:425–428

    Article  CAS  PubMed  Google Scholar 

  45. Šenolt L, Vencovský J, KPavelka K et al (2009) Prospective new biological therapies for rheumatoid arthritis. Autoimmun Rev 9:102–107

    Article  PubMed  Google Scholar 

  46. Smith PK, Krohn RI, Hermanson GT et al (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    Article  CAS  PubMed  Google Scholar 

  47. Sokal JE (1975) Measurement of delayed skin test responses. N Engl J Med 293:501–502

    Article  CAS  PubMed  Google Scholar 

  48. Suzuki M, Konya C, Goronzy JJ et al (2008) Inhibitory CD8+ T cells in autoimmune disease. Hum Immunol 69:781–789

    Article  CAS  PubMed  Google Scholar 

  49. Terato K, Haeper DS, Griffiths MM et al (1995) Collagen-induced arthritis in mice: synergistic effect of E. coli lipopolysaccharide bypasses epitope specificity in the induction of arthritis with monoclonal antibodies to type II collagen. Autoimmunity 22:137–147

    Article  CAS  PubMed  Google Scholar 

  50. Terato K, Hasty KA, Reife RA et al (1992) Induction of arthritis with monoclonal antibodies to collagen. J Immunol 148:2103–2108

    CAS  PubMed  Google Scholar 

  51. Tiegs G, Henstchel J, Wendel A (1992) A T-cell dependent experimental liver injury in mice inducible by concanavalin A. J Clin Invest 90:196–203

    Article  CAS  PubMed  Google Scholar 

  52. Uysal H, Bockermann R, Nandakumar KS et al (2009) Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis. J Exp Med 206:449–462

    Article  CAS  PubMed  Google Scholar 

  53. Ei Wakamatsu, Matsumoto I, Yoshiga Y et al (2009) Altered peptide ligands regulate type II collagen-induced arthritis in mice. Mod Rheumatol 19:366–371

    Article  Google Scholar 

  54. Winchester R (2003) Psoriatic arthritis. In: Freedberg IM, Eisen AZ, Wolff K, Austen FK, Goldsmith LA, Katz SI (eds) Fitzpatrick’s dermatology in general medicine, 6th edn. McGraw-Hill, New York, pp 427–436

    Google Scholar 

  55. Xi C, Tan L, Sun Y et al (2009) A novel recombinant peptide containing only two T-cell tolerance epitopes of chicken type II collagen that suppresses collagen-induced arthritis. Mol Immunol 46:729–737

    Article  CAS  PubMed  Google Scholar 

  56. Zügel U, Kaufmann SHE (1999) Role of heat shock proteins in protection from and pathogenesis of infectious diseases. Clin Microbiol Rev 12:19–39

    PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Jose Godoy for critical discussions, suggesting useful ideas and his excellent help as Medical Writer. Jose A. O’Daly, Astralis CSO, CEO and Chairman, would also like to thank The Technology Business Tax Certificate Transfer Program of the Greater State of New Jersey, Economic Development Authority (EDA). This study was realized in accordance with Home Office MD Biosciences Inflammation Discovery Services, Ltd, UK animal guidelines, and is performed following an application-form review by the Committee for Ethical Conduct in the Care and Use of Laboratory Animals. The study complies with the rules and regulations set forth.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jose Antonio O’Daly.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Daly, J.A., Gleason, J.P., Peña, G. et al. Purified proteins from leishmania amastigotes-induced delayed type hypersensitivity reactions and remission of collagen-induced arthritis in animal models. Arch Dermatol Res 302, 567–581 (2010). https://doi.org/10.1007/s00403-009-1026-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-009-1026-7

Keywords

Navigation