Journal of Clinical Immunology

, Volume 33, Issue 4, pp 876–879 | Cite as

Decreased Levels of Circulating CD4+CD25+Foxp3+ Regulatory T Cells in Patients with Primary Antiphospholipid Syndrome

  • Ester Rosári Raphaelli Dal Ben
  • Carine Hartmann do Prado
  • Talita Siara Almeida Baptista
  • Moisés Evandro Bauer
  • Henrique Luiz Staub
Brief Communication



CD4+CD25+Foxp3+ regulatory T (Treg) cell dysfunction has been documented in various autoimmune disorders, but not in antiphospholipid syndrome (APS) so far.


In this cross-sectional study, we aim to investigate CD4+CD25+Foxp3+ Treg cells, CD3+CD19 T cells and CD3CD19+ B cells in patients with primary APS and healthy controls. Cell subtypes were immunophenotyped using specific monoclonal antibodies (anti-CD3 CY5, anti-CD4 FITC, anti-CD25, anti-Foxp3, anti-CD19 PE) and flow cytometry.


Twenty patients with APS and 20 age- and sex-matched controls were studied. The percentage of total lymphocytes, activated Th cells (CD4+CD25+), Treg cells and CD3CD19+ B cells were found significantly lower in APS patients as compared to controls (all p < 0.05).


A dysfunction in CD4+CD25+Foxp3+ Treg cells may represent one of the mechanisms leading to autoimmunity in APS patients. The decreased number of CD3CD19+ B cells of APS patients warrants further elucidation.


Antiphospholipid syndrome CD4+CD25+Foxp3+ Treg cells CD3CD19+ B cells autoimmunity 


  1. 1.
    Palomo IG, Segovia FM, Alarcon ML, Fuentes BY, Pereira JG, Rojas A, et al. An insight into the pathophysiology of thrombosis in antiphospholipid syndrome. Front Biosci. 2007;12:3093–103.PubMedCrossRefGoogle Scholar
  2. 2.
    López-Pedrera C, Buendía P, Aguirre MA, Velasco F, Cuadrado MJ. Antiphospholipid syndrome and tissue factor: a thrombotic couple. Lupus. 2006;15:161–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, et al. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev. 2006;212:8–27.PubMedCrossRefGoogle Scholar
  4. 4.
    Yamaguchi T, Wing JB, Sakaguchi S. Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions. Semin Immunol. 2011;23:424–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Valencia X, Lipsky PE. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases. Nat Clin Pract Rheumatol. 2007;3:619–26.PubMedCrossRefGoogle Scholar
  7. 7.
    D’Hennezel E, Bin Dhuban K, Torgerson T, Piccirillo C. The immunogenetics of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2012;49:291–302.PubMedCrossRefGoogle Scholar
  8. 8.
    Peterson RA. Regulatory T-cells: diverse phenotypes integral to immune homeostasis and suppression. Toxicol Pathol. 2012;40:186–204.PubMedCrossRefGoogle Scholar
  9. 9.
    Bernard F, Romano A, Granel B. Regulatory T cells and systemic autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren’s syndrome. Rev Med Interne. 2010;31:116–27.PubMedCrossRefGoogle Scholar
  10. 10.
    Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.PubMedCrossRefGoogle Scholar
  11. 11.
    Moon HW, Kim BH, Park CM, Hur M, Yun YM, Kim SY, Lee MH. CD4+CD25highFoxP3+ regulatory T-cells in hematologic diseases. Korean J Lab Med. 2011;31(4):231–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Willis R, Harris EN, Pierangeli SS. Pathogenesis of the antiphospholipid syndrome. Semin Thromb Hemost. 2012;38:305–21.PubMedCrossRefGoogle Scholar
  13. 13.
    Meroni PL, Gerosa M, Raschi E, Scurati S, Grossi C, Borghi MO. Updating on the pathogenic mechanisms 5 of the antiphospholipid antibodies-associated pregnancy loss. Clin Rev Allergy Immunol. 2008;34:332–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Loser K, Beissert S. Regulatory T cells: banned cells for decades. J Invest Dermatol. 2012;132(3 Pt 2):864–71.PubMedCrossRefGoogle Scholar
  15. 15.
    Gómez-Puerta JA, Martín H, Amigo MC, Aguirre MA, Camps MT, Cuadrado MJ, et al. Long-term follow-up in 128 patients with primary antiphospholipid syndrome: do they develop lupus? Medicine (Baltimore). 2005;84:225–30.CrossRefGoogle Scholar
  16. 16.
    Genre J, Errante PR, Kokron CM, Toledo-Barros M, Câmara NO, Rizzo LV. Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: a link to autoimmunity? Clin Immunol. 2009;132:215–21.PubMedCrossRefGoogle Scholar
  17. 17.
    Hoehlig K, Shen P, Lampropoulou V, Roch T, Malissen B, O’Connor R, et al. Activation of CD4+Foxp3+ regulatory T cells proceeds normally in the absence of B cells during EAE. Eur J Immunol. 2012;42:1164–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Kuhn A, Beissert S, Krammer PH. CD4(+)CD25 (+) regulatory T cells in human lupus erythematosus. Arch Dermatol Res. 2009;301:71–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Alunno A, Bartoloni E, Bistoni O, Nocentini G, Ronchetti S, Caterbi S, et al. Balance between Regulatory T and Th17 cells in systemic Lupus Erythematosus: the old and the new. Clin Dev Immunol. 2012;2012:823085.PubMedCrossRefGoogle Scholar
  20. 20.
    Chen RL, Tao Y, Qiu KW, Huang WH, Huang CH, Li J. Association of circulating Treg cells with disease activity in patients with rheumatoid arthritis. Nan Fang Yi Ke Da Xue Xue Bao. 2012;32(6):886–9.PubMedGoogle Scholar
  21. 21.
    Torres-Aguilar H, Blank M, Kivity S, Misgav M, Luboshitz J, Pierangeli SS, et al. Tolerogenic dendritic cells inhibit antiphospholipid syndrome derived effector/memory CD4+ T cell response to β2GPI. Ann Rheum Dis. 2012;71:120–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Thompson JA, Perry D, Brusko TM. Autologous regulatory T cells for the treatment of type 1 diabetes. Curr Diab Rep. 2012. [Epub ahead of print].Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ester Rosári Raphaelli Dal Ben
    • 1
  • Carine Hartmann do Prado
    • 1
  • Talita Siara Almeida Baptista
    • 1
  • Moisés Evandro Bauer
    • 1
  • Henrique Luiz Staub
    • 2
  1. 1.Laboratory of Immunosenescence, Institute of Biomedical Research, Faculty of BiosciencesPontifical Catholic University of Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  2. 2.Rheumatology DepartmentSaint Lucas Hospital of PUCRSPorto AlegreBrazil

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