Skip to main content

Advertisement

SpringerLink
Log in

Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area

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

Abstract

Tuberculosis has emerged as a major concern in patients with immuno-mediated diseases, including psoriasis, undergoing treatment with biologicals. However, it is not known whether the chronically activated immune system of psoriasis patients interferes with their Mycobacterium tuberculosis (Mtb)-specific immunity, especially in tuberculosis-endemic areas like Brazil. We evaluated T-cell responses to a Mtb lysate and to the recombinant Mtb proteins ESAT-6 and Ag85B of tuberculin skin test (TST) positive and TST negative patients with severe or mild/moderate, untreated psoriasis in three different assays: lymphocyte proliferation, enzyme immunoassay for interferon (IFN)-γ and interleukin (IL)-10 production by peripheral blood mononuclear cells and overnight enzyme immunospot (ELISpot) for enumerating IFN-γ-secreting cells. In our cohort, a low proportion (29%) of the severe psoriasis patients tested were TST-positive. IFN-γ and IL-10 secretion and T-cell proliferation to Mtb antigens were reduced in TST-negative but not in TST-positive patients with severe psoriasis when compared to healthy controls with the same TST status. Similarly, severe psoriasis patients had decreased cytokine secretion and proliferative response to phytohemagglutinin. However, most psoriasis patients and healthy controls showed detectable numbers of IFN-γ-secreting effector-memory T-cells in response to Mtb antigens by ELISpot. TST-negative, mild/moderate psoriasis patients had responses that were mostly intermediary between TST-negative controls and severe psoriasis patients. Thus, patients with severe psoriasis possess decreased anti-Mtb central memory T-cell responses, which may lead to false-negative results in the diagnosis of TB infection, but retain T-cell memory-effector activity against Mtb antigens. We hypothesize that the latter may confer some protection against tuberculosis reactivation.

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
Fig. 2

Similar content being viewed by others

References

  1. Arend S, Geluk A, van Meijgaarden KE, van Dissel JT, Andersen P, Theisen M, Ottenhoff THM (2000) Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides. Infect Immun 68:3314–3321. doi:10.1128/IAI.68.6.3314-3321.2000

    Article  CAS  PubMed  Google Scholar 

  2. Bay ML, Lehrer A, Bressanelli A, Morini J, Bottasso O, Stanford J (1998) Psoriasis patients have T-cells with reduced responsiveness to common mycobacterial antigens. FEMS Immunol Med Microbiol 21:65–70. doi:10.1111/j.1574-695X.1998.tb01150.x

    Article  CAS  PubMed  Google Scholar 

  3. Castelo Filho A, Kritski AL, Barreto AW et al (2004) II Consenso Brasileiro de Tuberculose: Diretrizes Brasileiras para Tuberculose. J Bras Pneumol 30:24–35. doi:10.1590/S1806-37132004000700002

    Article  Google Scholar 

  4. Ekström Smedby K, Vajdic CM, Falster M et al (2008) Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood 111:4029–4038. doi:10.1182/blood-2007-10-119974

    Article  PubMed  Google Scholar 

  5. Emery P, Panayi GS, Welsh KI, Cole BC (1985) Relationship of HLA-DR4 to defective cellular immunity in rheumatoid arthritis using PPD, and mycoplasma and lectin mitogens. J Rheumatol 12:859–864

    CAS  PubMed  Google Scholar 

  6. Ferrara G, Losi M, D’Amico R et al (2006) Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet 367:1328. doi:10.1016/S0140-6736(06)68579-6

    Article  CAS  PubMed  Google Scholar 

  7. Ferrari VRMS, Dulley FL, Barros JCA, Duarte AJS, Benard G (2006) Distinct patterns of regeneration of central memory, effector memory and effector TCD8+ cell subsets after different hematopoietic cell transplant types: possible influence in the recovery of anti-cytomegalovirus immune response and risk for its reactivation. Clin Immunol 119:261–271. doi:10.1016/j.clim.2005.12.001

    Article  CAS  PubMed  Google Scholar 

  8. Geluk A, van Meijgaarden KE, Franken KL et al (2002) Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis. Infect Immun 70:2544–2548. doi:10.1128/IAI.70.5.2544-2548.2002

    Article  CAS  PubMed  Google Scholar 

  9. Girardi E, Goletti D, Ippolito G (2007) Should individuals who are tuberculin skin test negative and positive to RD1-IFN-gamma assay receive preventive therapy? Am J Respir Crit Care Med 175:198–199

    PubMed  Google Scholar 

  10. Griffiths CE, Barker JN (2007) Pathogenesis and clinical features of psoriasis. Lancet 370:263–271. doi:10.1016/S0140-6736(07)61128-3

    Article  CAS  PubMed  Google Scholar 

  11. Hill PC, Brookes RH, Fox A, Jackson-Sillah D, Lugos MD, Jeffries DJ, Donkor SA, Adegbola RA, McAdam KP (2006) Surprisingly high specificity of the PPD skin test for M. tuberculosis infection from recent exposure in the Gambia. Plos One 20:1e68

    Google Scholar 

  12. Hill PC, Jackson-Sillah DJ, Fox A et al (2008) Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts. PLoS One 3:1379. doi:10.1371/journal.pone.0001379

    Article  Google Scholar 

  13. Hoft DF, Worku S, Kampmann B et al (2002) Investigation of the relationships between immune-mediated inhibition of mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity. J Infect Dis 186:1448–1457. doi:10.1086/344359

    Article  CAS  PubMed  Google Scholar 

  14. Huebner RE, Schein MF, Bass JB Jr (1993) The tuberculin skin test. Clin Infect Dis 17:968–975

    CAS  PubMed  Google Scholar 

  15. Jacobs M, Togbe D, Fremond C et al (2007) Tumor necrosis factor is critical to control tuberculosis infection. Microbes Infect 9:623–628. doi:10.1016/j.micinf.2007.02.002

    Article  CAS  PubMed  Google Scholar 

  16. Jeffries DJ, Hill PC, Lugos M, Jackson-Sillah DJ, Adegbola RA, Brookes RH (2006) Identifying ELISPOT and skin test cut-offs for diagnosis of Mycobacterium tuberculosis infection in the Gambia. Int J Tuberc Lung Dis 10:192–198

    CAS  PubMed  Google Scholar 

  17. Kang YA, Lee HW, Yoon HI, Cho B, Han SK, Shim YS, Yim JJ (2005) Discrepancy between the tuberculin skin test and the whole-blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country. JAMA 293:2756–2761. doi:10.1001/jama.293.22.2756

    Article  CAS  PubMed  Google Scholar 

  18. Krueger JG, Bowcock A (2005) Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis 64:30–36. doi:10.1136/ard.2004.031120

    Article  Google Scholar 

  19. Lalvani A, Brookes R, Wilkinson RJ, Malin AS, Pathan AA, Andersen P, Dockrell H, Pasvol G, Hill AV (1998) Human cytolytic and interferon gamma-secreting CD8+ T lymphocytes specific for Mycobacterium tuberculosis. Proc Natl Acad Sci USA 95:270–275. doi:10.1073/pnas.95.1.270

    Article  CAS  PubMed  Google Scholar 

  20. Launois P, DeLeys R, Niang MN et al (1994) T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in tuberculosis and leprosy. Infect Immun 62:3679–3687

    CAS  PubMed  Google Scholar 

  21. Lindegård B (1986) Diseases associated with psoriasis in a general population of 159,200 middle-aged, urban, native Swedes. Dermatologica 172:298–304

    Article  PubMed  Google Scholar 

  22. Marchant A, Amedei A, Azzurri A et al (2001) Polarization of PPD-specific T-cell response of patients with tuberculosis from Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-α or interleukin-12. Am J Respir Cell Mol Biol 24:187–194

    CAS  PubMed  Google Scholar 

  23. Mendonça M, Tanji MM, Silva LC, Silveira GG, Oliveira SC, Duarte AJ, Benard G (2007) Deficient in vitro anti-mycobacterial immunity despite successful long-term highly active antiretroviral therapy in HIV-infected patients with past history of tuberculosis infection or disease. Clin Immunol 125:60–66. doi:10.1016/j.clim.2007.06.002

    Article  PubMed  Google Scholar 

  24. Paimela L, Johansson-Stephansson EA, Koskimies S, Leirisalo-Repo M (1990) Depressed cutaneous cell-mediated immunity in early rheumatoid arthritis. Clin Exp Rheumatol 8:433–437

    CAS  PubMed  Google Scholar 

  25. Pereira CB, Palaci M, Leite OHM, Duarte AJS, Benard G (2004) Monocyte cytokine secretion in patients with pulmonary tuberculosis differs from that of healthy infected subjects and correlates with clinical manifestations. Microbes Infect 6:25–33. doi:10.1016/j.micinf.2003.10.007

    Article  CAS  PubMed  Google Scholar 

  26. Ponce de Leon D, Acevedo-Vasquez E, Sanchez-Torres A et al (2005) Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis. Ann Rheum Dis 64:1360–1361. doi:10.1136/ard.2004.029041

    Article  CAS  PubMed  Google Scholar 

  27. Ponchel F, Morgan AW, Bingham SJ et al (2002) Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood 100:4550–4556. doi:10.1182/blood-2002-03-0671

    Article  CAS  PubMed  Google Scholar 

  28. Raval A, Akhavan-Toyserkani G, Brinker A, Avigan M (2007) Brief communication: characteristics of spontaneous cases of tuberculosis associated with infliximab. Ann Intern Med 147:699–702

    PubMed  Google Scholar 

  29. Richeldi L (2006) An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med 174:736–742. doi:10.1164/rccm.200509-1516PP

    Article  PubMed  Google Scholar 

  30. Smith CH, Anstey AV, Barker JN, British Association of Dermatologists (2005) British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005. Br J Dermatol 153:486–497. doi:10.1111/j.1365-2133.2005.06893.x

    Article  CAS  PubMed  Google Scholar 

  31. Souza TNL Avaliação da prevalência da infecção por Mycobacterium tuberculosis entre os profissionais de saúde do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. São Paulo, 1999 Dissertação (Mestrado) – Departamento de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo

  32. Sugiyama H, Gyulai R, Toichi E, Garaczi E, Shimada S, Stevens SR, McCormick TS, Cooper KD (2005) Dysfunctional blood and target tissue CD4+CD25 high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol 174:164–173

    CAS  PubMed  Google Scholar 

  33. Tzu J, Kerdel F (2008) From conventional to cutting edge: the new era of biologics in treatment of psoriasis. Dermatol Ther 21:131–141. doi:10.1111/j.1529-8019.2008.00180.x

    Article  PubMed  Google Scholar 

  34. Wallis RS, Broder M, Wong J, Lee A, Hoq L (2005) Reactivation of latent granulomatous infections by infliximab. Clin Infect Dis 41:194–198. doi:10.1086/429996

    Article  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge Ana Paula Kipnis and Moisés Palaci for their help with the antigens, and Tom Ottenhoff for reviewing the manuscript. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (contracts # 05/57761-7 and 05/60075-8) and by Schering-Plough Pharmaceutical and Wyeth Pharmaceutical, the Netherlands Leprosy Relief Foundation (NLR) and the European Commission. GB and AJSD are senior researchers from Conselho Nacional para o Desenvolvimento Científico e Tecnológico.

Conflict of interest statement

All authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Laboratory of Dermatology and Immunodeficiencies, Medical School of the University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500 3º. Floor, Sao Paulo, Brazil

    Léia C. R. Silva, Guilherme G. Silveira, Alberto José da Silva Duarte & Gil Benard

  2. Division of Clinical Dermatology, Hospital das Clínicas, Medical School of the University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar 255, Sao Paulo, Brazil

    Marcelo Arnone, Ricardo Romiti & Maria Denise Fonseca Takahashi

  3. Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

    Annemiek Geluk & Kees C. L. M. Franken

Authors
  1. Léia C. R. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guilherme G. Silveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcelo Arnone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ricardo Romiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annemiek Geluk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kees C. L. M. Franken
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alberto José da Silva Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria Denise Fonseca Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gil Benard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gil Benard.

About this article

Cite this article

Silva, L.C.R., Silveira, G.G., Arnone, M. et al. Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area. Arch Dermatol Res 302, 255–262 (2010). https://doi.org/10.1007/s00403-009-0982-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-009-0982-2

Keywords

Search

Navigation