Skip to main content

Advertisement

Log in

Antigens from Leishmania amastigotes inducing clinical remission of psoriatic arthritis

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

Abstract

A first generation vaccine (AS100-1) was manufactured with protein from four cultured Leishmania species, which proved to be effective in the treatment of psoriasis. A single blind trial on 3,132 psoriasis patients revealed 508 (16.2%) subjects with psoriatic arthritis (PsA) that received AS100-1 antigens. The study group was distributed according to percent psoriasis area and severity index (PASI) reduction from PASI 10 to PASI 100. All groups decreased in arthritis score (AS), tender joints counts and nail changes after treatment; the highest decreased in the PASI 100 group. Relapses of psoriasis and PsA had PASI and AS lower than initial values before treatment. Clinical remissions were at lower doses and less time, after the second course of treatment. Peripheral blood mononuclear cells (PBMC) lymphocyte subsets (LS) varied with PASI range (1–10, 11–20 and 21–72). Pre-treatment, absolute values of gated LS: CD4+, CD8+HLA−, CD8+HLA+, CD8+CD3−, CD8+CD3+ decreased in PBMC as PASI increased, suggesting migration from the blood to the skin. In contrary to the previous finding, the following LS: CD8+CD4−, CD3+CD8−, HLA+CD8−, CD19, CD8+CD4+ and membrane surface immunoglobulin IgA+, IgD+, IgM+, IgE+, and IgG+ increased in PBMC as PASI increased suggesting activation and proliferation by unknown antigens creating a homeostatic cycle between skin/joints and peripheral blood. After nine doses of AS100-1, the following LS: CD8+CD3+, CD8+HLA+, CD3+CD8−, CD4+CD8−, CD8+HLA−, HLA+CD8−, CD8+CD3−, CD19+, CD8+CD4−, CD8+CD4+, IgA+, IgD+, IgM+, IgE+, and IgG+ decreased significantly as compared with values before treatment. The LS decreased stops the vicious cycle between skin/joints and blood explaining clinical remission of lesions.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Amherd-Hoekstra A, Näher H, Lorenz HM et al (2010) Psoriatic arthritis: a review. J Dtsch Dermatol Ges 8:332–339

    Article  PubMed  Google Scholar 

  2. Barton AC (2002) Genetic epidemiology. Psoriatic arthritis. Arthritis Res 4:247–251

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Brewer JM (2006) (How) do aluminium adjuvants work? Immunol Lett 102:10–15

    Article  PubMed  CAS  Google Scholar 

  5. Brockbank JE, Stein M, Schentag CT et al (2005) Dactylitis in psoriatic arthritis: a marker for disease severity? Ann Rheum Dis 64:188–190

    Article  PubMed  CAS  Google Scholar 

  6. Cassell SE, Bieber JD, Rich P et al (2007) The modified nail psoriasis severity index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis. J Rheumatol 2007 34:123–129

    Google Scholar 

  7. Ceponis A, Kavanaugh A (2010) Treatment of psoriatic arthritis with biological agents. Semin Cutan Med Surg 29:56–62

    Article  PubMed  CAS  Google Scholar 

  8. Chandran V, Gottlieb A, Cook RJ et al (2009) Psoriatic arthritis international multicenter psoriasis and psoriatic arthritis reliability trial for the assessment of skin, joints, nails, and dactylitis. Arthritis Rheum 61:1235–1242

    Article  PubMed  Google Scholar 

  9. Chandran V, Raychaudhuri SP (2010) Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 34:314–321

    Article  Google Scholar 

  10. Chandran V, Schentag CT, Gladman DD (2007) Sensitivity of the classification of psoriatic arthritis criteria in early psoriatic arthritis. Arthritis Rheum 57:1560–1563

    Article  PubMed  Google Scholar 

  11. Chang YT, Chen TJ, Liu PC et al (2009) Epidemiological study of psoriasis in the national health insurance database in Taiwan. Acta Derm Venereol 89:262–266

    Article  PubMed  Google Scholar 

  12. Choy E (2007) T cells in psoriatic arthritis. Curr Rheumatol Rep 9:437–441

    Article  PubMed  CAS  Google Scholar 

  13. Choy MK, Phipps ME (2010) MICA polymorphism: biology and importance in immunity and disease. Trends Mol Med 16:97–106

    Article  PubMed  CAS  Google Scholar 

  14. Christophers E, Barker JN, Griffiths CE et al (2010) The risk of psoriatic arthritis remains constant following initial diagnosis of psoriasis among patients seen in European dermatology clinics. J Eur Acad Dermatol Venereol 24:548–554

    Article  PubMed  CAS  Google Scholar 

  15. Ciocon DH, Kimball AB (2007) Psoriasis and psoriatic arthritis: separate or one and the same? Br J Dermatol 157:850–860

    Article  PubMed  CAS  Google Scholar 

  16. Coates LC, Helliwell PS (2008) Classification and categorization of psoriatic arthritis. Clin Rheumatol 27:1211–1216

    Article  PubMed  Google Scholar 

  17. Costello P, Bresnihan B, O’Farrelly C et al (1999) Predominance of CD8+ T lymphocytes in psoriatic arthritis. J Rheumatol 26:1117–1124

    PubMed  CAS  Google Scholar 

  18. Elder JT (2009) Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis. Genes Immun 10:201–209

    Article  PubMed  CAS  Google Scholar 

  19. Englbrecht M, Wang Y, Ronneberger M et al (2010) Measuring joint involvement in polyarticular psoriatic arthritis: an introduction of alternatives. Arthritis Care Res 62:977–983

    Article  CAS  Google Scholar 

  20. Filaci G, Fenoglio D, Indiveri F (2011) CD8(+) T regulatory/suppressor cells and their relationships with autoreactivity and autoimmunity. Autoimmunity 44:51–57

    Article  PubMed  CAS  Google Scholar 

  21. Filaci G, Rizzi M, Setti M et al (2005) Non-antigen-specific CD8(+) T suppressor lymphocytes in diseases characterized by chronic immune responses and inflammation. Ann N Y Acad Sci 1050:115–123

    Article  PubMed  CAS  Google Scholar 

  22. Fink AM, Cauza E, Hassfeld W et al (2007) Vascular endothelial growth factor in patients with psoriatic arthritis. Clin Exp Rheumatol 25:305–308

    PubMed  CAS  Google Scholar 

  23. FitzGerald O, Winchester R (2009) Psoriatic arthritis: from pathogenesis to therapy. Arthritis Res Ther 11:214–223

    Article  PubMed  Google Scholar 

  24. Gabriel SE, Michaud K (2009) Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther 11:229–245

    Article  PubMed  Google Scholar 

  25. González S, Martínez-Borra J, López-Vázquez A et al (2002) MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. J Rheumatol 29:973–978

    PubMed  Google Scholar 

  26. Griffiths EMG, Barker JN (2007) Pathogenesis and clinical features of psoriasis. Lancet 370:263–271

    Article  PubMed  CAS  Google Scholar 

  27. Ibrahim G, Waxman R, Helliwell PS (2009) The prevalence of psoriatic arthritis in people with psoriasis. Arthritis Rheum 61:1373–1378

    Article  PubMed  CAS  Google Scholar 

  28. Jandus C, Bioley G, Rivals JP et al (2008) Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 58:2307–2317

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  30. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193(1):265–275

    PubMed  CAS  Google Scholar 

  31. 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 

  32. McGonagle D, Lories RJU, Tan AL et al (2007) The concept of a “synovio-entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 56:2482–2491

    Article  PubMed  Google Scholar 

  33. McGonagle D (2009) Enthesitis: an autoinflammatory lesion linking nail and joint involvement in psoriatic disease. J Eur Acad Dermatol Venereol 23:9–13

    Article  PubMed  CAS  Google Scholar 

  34. Mease P (2006) Psoriatic arthritis update. Bull NYU Hosp Jt Dis 64:25–31

    PubMed  Google Scholar 

  35. Mease PJ (2010) Psoriatic arthritis: pharmacotherapy update. Curr Rheumatol Rep 12:272–280

    Article  PubMed  CAS  Google Scholar 

  36. Mrowietz U, Reich K (2009) Psoriasis—new insights into pathogenesis and treatment. Dtsch Arztebl Int 106:11–19

    PubMed  Google Scholar 

  37. Mrowietz U, Elder JT, Barker J (2007) The importance of disease associations and concomitant therapy for the long term management of psoriasis patients. Arch Dermatol Res 298:309–319

    Article  Google Scholar 

  38. O’Daly JA, Gleason J (2010) Antigens from Leishmania amastigotes inducing clinical remission of psoriasis: relationship between leishmaniasis and psoriasis. DERMA 1:47–57

    Google Scholar 

  39. O’Daly JA, Gleason JP, Peña G et al (2010) 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

    Article  PubMed  Google Scholar 

  40. 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 301:411–427

    Article  PubMed  Google Scholar 

  41. 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 

  42. O’Daly JA, Rodriguez B, Ovalles T et al (2010) Lymphocyte subsets in peripheral blood of patients with psoriasis before and after treatment with leishmania antigens. Arch Dermatol Res 302:95–104

    Article  PubMed  Google Scholar 

  43. O’Daly JA, Rodriguez MB (1988) Differential growth requirements of several leishmania spp in chemically defined culture media. Acta Trop Basel 45:109–126

    PubMed  Google Scholar 

  44. Radtke MA, Reich K, Blome C et al (2009) Prevalence and clinical features of psoriatic arthritis and joint complaints in patients with psoriasis: results of a German national survey. J Eur Acad Dermatol Venereol 23:683–691

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  46. Reich K, Kruger K, Mossner R et al (2009) Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasis. Br J Dermatol 160:1040–1047

    Article  PubMed  CAS  Google Scholar 

  47. Rimaniol AC, Gras G, Clayette P (2007) In vitro interactions between macrophages and aluminum-containing adjuvants. Vaccine 25:6784–6792

    Article  PubMed  CAS  Google Scholar 

  48. Rimaniol AC, Gras G, Verdier F et al (2004) Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type. Vaccine 22:3127–3135

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  50. Saber TP, Ng CT, Renard G et al (2010) Remission in psoriatic arthritis: is it possible and how can it be predicted? Arthritis Res Ther 12:R94

    Article  PubMed  Google Scholar 

  51. Sala P, Tonutti E, Feruglio C et al (1993) Persistent expansions of CD4+ CD8+ peripheral blood T cells. Blood 82:1546–1552

    PubMed  CAS  Google Scholar 

  52. Salliot C, Dernis E, Lavie F et al (2009) Diagnosis of peripheral psoriatic arthritis: recommendations for clinical practice based on data from the literature and experts opinion. Joint Bone Spine Joint Bone Spine 76:532–539

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  54. Soriano ER, Rosa J (2009) Update on the treatment of peripheral arthritis in psoriatic arthritis. Curr Rheumatol Rep 11:270–277

    Article  PubMed  CAS  Google Scholar 

  55. Taylor W, Gladman D, Helliwell P et al (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54:2665–2673

    Article  PubMed  Google Scholar 

  56. Tonui WK, Mejia JS, Hochberg L et al (2004) Immunization with Leishmania major exogenous antigens protects susceptible BALB/c mice against challenge infection with L major. Infect Immun 72:5654–5661

    Article  PubMed  CAS  Google Scholar 

  57. Trautmann A, Rückert B, Schmid-Grendelmeier P et al (2003) Human CD8 T cells of the peripheral blood contain a low CD8 expressing cytotoxic/effector subpopulation. Immunology 108:305–312

    Article  PubMed  CAS  Google Scholar 

  58. Ulanova M, Tarkowski A, Hahn-Zoric M et al (2001) The common vaccine adjuvant aluminum hydroxide up-regulates accessory properties of human monocytes via an interleukin-4-dependent mechanism. Infect Immun 69:1151–1159

    Article  PubMed  CAS  Google Scholar 

  59. van Kuijk AW, Reinders-Blankert P, Smeets TJ et al (2006) Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis 65:1551–1557

    Article  PubMed  Google Scholar 

  60. Weger W (2010) Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents. Br J Pharmacol 160:810–820

    PubMed  CAS  Google Scholar 

  61. Winchester R, Minevich G, Kane D et al (2008) Heterogeneity of the psoriasis phenotype revealed by HLA class I haplotype associations in psoriatic arthritis and psoriasis. Clin Immunol 127:S88–S89

    Article  Google Scholar 

  62. Winchester R (2004) The genetics of autoimmune-mediated rheumatic diseases: clinical and biologic implications. Rheum Dis Clin North Am 30:213–227

    Article  PubMed  Google Scholar 

  63. Wollina U, Unger L, Heinig B, Kittner T (2010) Psoriatic arthritis. Dermatol Ther 23:123–136

    Article  PubMed  Google Scholar 

  64. 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

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) and to the Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICIT) for its support, under contract # RP-IV-120030, while Dr. O’Daly was in Caracas, Venezuela.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. A. O’Daly.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Daly, J.A., Gleason, J., Lezama, R. et al. Antigens from Leishmania amastigotes inducing clinical remission of psoriatic arthritis. Arch Dermatol Res 303, 399–415 (2011). https://doi.org/10.1007/s00403-011-1133-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-011-1133-0

Keywords

Navigation