Auto-immunity profile evaluation during different clinical manifestations of Behçet disease in Algerian patients: effect of corticosteroid treatment

  • Fatmazohra Djaballah-Ider
  • Abdelhamid Djaballah
  • Zineb Djeraba
  • Samia Chaib
  • Chafia Touil-BoukoffaEmail author
Original Article


Background and aims

Behçet disease (BD) is a chronic multisystem disease. It stands at the crossroads between the auto-immunity and auto-inflammatory disorders. Our study aims to evaluate corticosteroids therapy effects on serum immunoglobulin isotypes and anti-phospholipid auto-anti-body production in Algerian BD patients with different clinical manifestations.


We evaluated serum immunoglobulin isotypes and anti-phospholipid (anti-cardiolipin, anti-β2glycoprotein I, anti-prothrombin) auto-anti-body production using Turbidimetric or Luminex platform assays. Our study was conducted in naïve active BD patients and in corticosteroid-treated patients with different clinical manifestations.

Results and discussion

Our results indicate that IgM, IgG, and IgA levels were higher in naïve active patients. The increase in sera isotypes did not differ according to the clinical manifestation, except for IgA production, which was associated with an increased risk of mucocutaneous and ocular involvement. Interestingly, in corticosteroid-treated active patients, no difference was reported between each clinical subgroup. Furthermore,anti-cardiolipin, anti-β2glycoprotein I and anti-prothrombin auto-anti-body levels were elevated in naïve active patients. Contrary to anti-prothrombin, high anti-cardiolipin and anti-β2glycoprotein I, production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and ocular involvement. Importantly, corticosteroid therapy significantly reduced these immune markers regardless of the clinical manifestations.


Our results suggest that high IgA production could be a risk marker of uveitis in naïve active patients. Moreover, concomitant high anti-cardiolipin, anti-β2glycoprotein I and anti-prothrombin production is related to an increased risk of mucocutaneous lesions, ocular and vascular involvement. Collectively, our data indicate the importance of evaluating the corticosteroid effect on immune responses associated with BD to ensure an adequate investigation of each related clinical manifestation.


Behçet Immunoglobulin isotypes Auto-anti-bodies 



The authors thank the patients and the controls. They also express their gratitude to the Department of Immunology of Dr Md SeghirNEKKACHE Hospital in Algiers.


This work was supported by grants from National Agency for Research and Development (ATRSS, ex ANDRS), project code number43-ANDRS-2011 Algeria.

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no conflicts of interest with regard to the research, authorship, and/or publication of this article.

Ethical approval

This manuscript was approved by all co-authors. The local ethics committee “Algerian National Agency for Research in Health Sciences, ATRSS ex-ANDRS” in compliance with Helsinki declaration has approved our study (Code number 43-ANDRS-2011).


  1. Alekberova ZS, Prokaeva TB, Reshetniak TM et al (2000) Antiphospholipid anti-bodies in Behcet’s disease. Klin Med 78(5):37–38Google Scholar
  2. Ataollahi MR, Aflaki E, Nazarinia MA et al (2012) anti-cardiolipin and anti-neutrophil cytoplasmic anti-bodies in Iranian patients with Behcet’s disease. Iran J Immunol 9(4):241–247Google Scholar
  3. Bardak Y, Aridoğan BC (2004) The demonstration of serum interleukin 6–8, tumor necrosis factor-alpha, complement, and immunoglobulin levels in Behçet’s disease with ocular involvement. Ocul Immunol Inflamm 12(1):53–58CrossRefGoogle Scholar
  4. Caramaschi P, Poli G, Bonora A et al (2010) A study on thrombophilic factors in Italian Behcet’s patients. Joint Bone Spine 77(4):330–334. CrossRefGoogle Scholar
  5. Cho SB, Zheng Z, Ahn KJ et al (2013) Serum IgA reactivity against GroEL of Streptococcus sanguinis and human heterogeneous nuclear ribonucleoprotein A2/B1 in Patients with Behçet disease. Br J Dermatol 168(5):977–983. CrossRefGoogle Scholar
  6. Coit P, Direskeneli H, Sawalha AH (2018) An update on the role of epigenetics in systemic vasculitis. Curr Opin Rheumatol 30(1):4–15. CrossRefGoogle Scholar
  7. Davatchi F, Shahram F, Chams-Davatchi C et al (2010) Behcet’s disease: from east to west. Clin Rheumatol 29(8):823–833. CrossRefGoogle Scholar
  8. Direskeneli H (2006) auto-immunity vs auto-inflammation in Behcet’s disease: do we oversimplify a complex disorder? Rheumatology 45(12):1461–1465. CrossRefGoogle Scholar
  9. Djaballah-Ider F, Chaib S, Belguendouz H et al (2012) T cells activation and interferon-γ/nitric oxide production during Behçet disease: a study in Algerian patients. Ocul Immunol Inflamm 20(3):215–217. CrossRefGoogle Scholar
  10. Djaballah-Ider F, Djeraba Z, Chemli M et al (2018) Influence of corticosteroid therapy on IL-18 and nitric oxide production during Behçet’s disease. Inflammopharmacology. Google Scholar
  11. Ekşioglu-Demiralp E, Kibaroglu A, Direskeneli H et al (1999) Phenotypic characteristics of B cells in Behçet’s disease: increased activity in B cell subsets. J Rheumatol 26(4):826–832Google Scholar
  12. El-Ageb EM, Al-Maini MH, Al-Shukaily AK et al (2002) Clinical features of Behçet’s disease in patients in the sultanate of Oman; the significance of antiphospholipid anti-bodies? Rheumatol Int 21(5):176–181CrossRefGoogle Scholar
  13. Erdağ E, Şahin C, Küçükali Cİ et al (2017) Effects of in vivo and in vitro administration of neuro-Behcet’s disease IgG. Neurol Sci 38(5):833–843. CrossRefGoogle Scholar
  14. Erdoğan S, Sorgun MH, Yalçındağ N et al (2015) Bilateral optic neuritis in a patient with Behçet’s disease who respond to therapeutic plasma exchange. Saudi J Ophthalmol 29(4):298–300. CrossRefGoogle Scholar
  15. Galli M, Comfurius P, Barbui T et al (1992) Anticoagulant activity of beta 2-glycoprotein I is potentiated by a distinct subgroup of anticardiolipin anti-bodies. Thromb Haemost 68(3):297–300CrossRefGoogle Scholar
  16. Garcia-Rivero AA, Gonzalez-Argote J, Martínez Larrarte JP et al (2017) Neuroimmunological response in neuro-Behçet’s. Reumatol Clin. Google Scholar
  17. Gorbacheva V, Ayasoufi K, Fan R et al (2015) B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) mediate CD40-independent help by memory CD4 T cells. Am J Transpl 15(2):346–357. CrossRefGoogle Scholar
  18. Guenane H, Hartani D, Chachoua L et al (2006) Production of Th1/Th2 cytokines and nitric oxide in Behçet’s uveitis and idiopathic uveitis. J Fr Ophtalmol 29(2):146–152CrossRefGoogle Scholar
  19. Gül A (2015) Pathogenesis of Behçet’s disease: auto-inflammatory features and beyond. Semin Immunopathol 37(4):413–418. CrossRefGoogle Scholar
  20. Hamzaoui K, Hamzaoui A, Guemira F et al (2002) Cytokine profile in Behçet’s disease patients. Relationship with disease activity. Scand J Rheumatol 31(4):205–210CrossRefGoogle Scholar
  21. Hamzaoui K, Houman H, Ben Dhifallah I et al (2008) Serum BAFF levels and skin MRNA expression in patients with Behçet’s disease. Clin Exp Rheumatol 26(4 Suppl 50):S64–71Google Scholar
  22. Higashihara T, Okada A, Kusano T et al (2017) A novel case of renal pathergy reaction in a Behçet’s disease patient complicated by IgA vasculitis. BMC Nephrol 18(1):40. CrossRefGoogle Scholar
  23. Kandolf-Sekulovic L, Pavlovic MD, Glisic B et al (2005) Adamantiades-Behçet’s disease, deep venous thrombosis and anticardiolipin anti-bodies: report of two cases. J Eur Acad Dermatol Venereol 19(4):484–486. CrossRefGoogle Scholar
  24. Kang HJ, Lee YW, Han SH et al (1998) Anticardiolipin and anti-beta2-glycoprotein I anti-bodies in Behcet’s disease. J Korean Med Sci 13(4):400–404. CrossRefGoogle Scholar
  25. Kang SE, Lee SJ, Lee JY et al (2017) Serum levels of IgG anti-bodies against alpha-enolase are increased in patients with Behçet’s disease and are associated with the severity of oral ulcer, erythrocyte sedimentation rates, and C-reactive protein. Clin Exp Rheumatol 35 Suppl 108(6):67–74Google Scholar
  26. Kapsimali VD, Kanakis MA, Vaiopoulos GA et al (2010) Etiopathogenesis of Behçet’s disease with emphasis on the role of immunological aberrations. Clin Rheumatol 29(11):1211–1216. CrossRefGoogle Scholar
  27. Kawakami T, Yamazaki M, Mizoguchi M et al (2009) Antiphosphatidylserine-prothrombin complex anti-bodies in 3 patients with Behçet disease involving superficial vein thrombophlebitis. Arch Dermatol 145(2):171–175. CrossRefGoogle Scholar
  28. Khairallah M, Accorinti M, Muccioli C et al (2012) Epidemiology of Behçet disease. Ocul Immunol Inflamm 20(5):324–335. CrossRefGoogle Scholar
  29. LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112(5):1570–1580. CrossRefGoogle Scholar
  30. McGonagle D, McDermott MF (2006) A proposed classification of the immunological diseases. PLoS Med 3(8):e297. CrossRefGoogle Scholar
  31. Mendoza-Pinto C, García-Carrasco M, Jiménez-Hernández M et al (2010) Etiopathogenesis of Behçet’s disease. Auto-immun Rev 9(4):241–245. CrossRefGoogle Scholar
  32. Musabak U, Baylan O, Cetin T et al (2005) Lipid profile and anticardiolipin anti-bodies in Behcet’s disease. Arch Med Res 36(4):387–392. CrossRefGoogle Scholar
  33. Musabak U, Pay S, Erdem H et al (2006) Serum interleukin-18 levels in patients with Behçet’s disease. Is its expression associated with disease activity or clinical presentations? Rheumatol Int 26(6):545–550. CrossRefGoogle Scholar
  34. Nakanishi K, Yoshimoto T, Tsutsui H et al (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474. CrossRefGoogle Scholar
  35. Ohno S, Ohguchi M, Hirose S et al (1982) Close association of HLA-Bw51 with Behçet’s disease. Arch Ophthalmol Chic Ill 1960 100(9):1455–1458CrossRefGoogle Scholar
  36. Park SJ, Oh JY, Shin JI (2014) Could increased IgA induced by BAFF be the cause of IgA nephropathy development in Behcet’s disease? Comment on: Behcet’s disease and IgA nephropathy (Rheumatol Int. 2012 Jul; 32(7):2227–9). Rheumatol Int 34(2):283–284. CrossRefGoogle Scholar
  37. Pereira RM, Gonçalves CR, Bueno C et al (1989) Anticardiolipin anti-bodies in Behçet’s syndrome: a predictor of a more severe disease. Clin Rheumatol 8(2):289–291CrossRefGoogle Scholar
  38. Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behçet’s disease. N Engl J Med 341(17):1284–1291. CrossRefGoogle Scholar
  39. Scherrer MAR, Rocha VB, Garcia LC (2017) Behçet’s disease: review with emphasis on dermatological aspects. An Bras Dermatol 92(4):452–464. CrossRefGoogle Scholar
  40. Suzuki N, Sakane T, Ueda Y, Tsunematsu T (1986) Abnormal B cell function in patients with Behçet’s disease. Arthritis Rheum 29(2):212–219CrossRefGoogle Scholar
  41. Tokay S, Direskeneli H, Yurdakul S et al (2001) Anticardiolipin anti-bodies in Behçet’s disease: a reassessment. Rheumatol Oxf Engl. 40(2):192–195CrossRefGoogle Scholar
  42. Trottier MD, Newsted MM, King LE, Fraker PJ (2008) Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function. Proc Natl Acad Sci USA 105(6):2028–2033. CrossRefGoogle Scholar
  43. Tursen U (2009) Activation markers in Behcet’s disease. Urkderm Arch Turk Dermatol Venerol 43:74–86Google Scholar
  44. Yoon JY, Lee Y, Yu SL et al (2017) Aberrant expression of interleukin-10 and activation-induced cytidine deaminase in B cells from patients with Behçet’s disease. Biomed Rep 7(6):520–526. Google Scholar
  45. Zhou ZY, Chen SL, Shen N, Lu Y (2012) Cytokines and Behcet’s disease. Auto-immun Rev 11(10):699–704. CrossRefGoogle Scholar
  46. Zivkovic M, Zlatanovic M, Zlatanovic G et al (2011) Anticardiolipin anti-bodies in patients with Behcet’s disease. Bosn J Basic Med Sci 11(1):58–61CrossRefGoogle Scholar
  47. Zouboulis CC, Büttner P, Tebbe B et al (1993) Anticardiolipin anti-bodies in Adamantiades-Behçet’s disease. Br J Dermatol 128(3):281–284CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Fatmazohra Djaballah-Ider
    • 1
  • Abdelhamid Djaballah
    • 2
  • Zineb Djeraba
    • 1
  • Samia Chaib
    • 3
  • Chafia Touil-Boukoffa
    • 1
    Email author
  1. 1.Cytokines and NO-Synthases, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological ScienceUSTHBAlgiersAlgeria
  2. 2.Department of NephrologyDr Md Seghir NEKKACHE HospitalAlgiersAlgeria
  3. 3.Department of ImmunologyDr Md Seghir NEKKACHE HospitalAlgiersAlgeria

Personalised recommendations