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.
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Alekberova ZS, Prokaeva TB, Reshetniak TM et al (2000) Antiphospholipid anti-bodies in Behcet’s disease. Klin Med 78(5):37–38
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):241–247
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):53–58
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. https://doi.org/10.1016/j.jbspin.2010.02.022
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. https://doi.org/10.1111/bjd.12128
Coit P, Direskeneli H, Sawalha AH (2018) An update on the role of epigenetics in systemic vasculitis. Curr Opin Rheumatol 30(1):4–15. https://doi.org/10.1097/BOR.0000000000000451
Davatchi F, Shahram F, Chams-Davatchi C et al (2010) Behcet’s disease: from east to west. Clin Rheumatol 29(8):823–833. https://doi.org/10.1007/s10067-010-1430-6
Direskeneli H (2006) auto-immunity vs auto-inflammation in Behcet’s disease: do we oversimplify a complex disorder? Rheumatology 45(12):1461–1465. https://doi.org/10.1093/rheumatology/kel329
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. https://doi.org/10.3109/09273948.2012.671882
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. https://doi.org/10.1007/s10787-018-0472-2
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):826–832
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):176–181
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. https://doi.org/10.1007/s10072-017-2856-2
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. https://doi.org/10.1016/j.sjopt.2015.05.003
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):297–300
Garcia-Rivero AA, Gonzalez-Argote J, Martínez Larrarte JP et al (2017) Neuroimmunological response in neuro-Behçet’s. Reumatol Clin. https://doi.org/10.1016/j.reuma.2017.02.005
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. https://doi.org/10.1111/ajt.12984
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):146–152
Gül A (2015) Pathogenesis of Behçet’s disease: auto-inflammatory features and beyond. Semin Immunopathol 37(4):413–418. https://doi.org/10.1007/s00281-015-0502-8
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):205–210
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):S64–71
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. https://doi.org/10.1186/s12882-017-0451-7
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. https://doi.org/10.1111/j.1468-3083.2005.01193.x
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. https://doi.org/10.3346/jkms.19126.96.36.1990
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):67–74
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. https://doi.org/10.1007/s10067-010-1491-6
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. https://doi.org/10.1001/archdermatol.2008.570
Khairallah M, Accorinti M, Muccioli C et al (2012) Epidemiology of Behçet disease. Ocul Immunol Inflamm 20(5):324–335. https://doi.org/10.3109/09273948.2012.723112
LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112(5):1570–1580. https://doi.org/10.1182/blood-2008-02-078071
McGonagle D, McDermott MF (2006) A proposed classification of the immunological diseases. PLoS Med 3(8):e297. https://doi.org/10.1371/journal.pmed.0030297
Mendoza-Pinto C, García-Carrasco M, Jiménez-Hernández M et al (2010) Etiopathogenesis of Behçet’s disease. Auto-immun Rev 9(4):241–245. https://doi.org/10.1016/j.autrev.2009.10.005
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. https://doi.org/10.1016/j.arcmed.2005.03.019
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. https://doi.org/10.1007/s00296-005-0029-8
Nakanishi K, Yoshimoto T, Tsutsui H et al (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474. https://doi.org/10.1146/annurev.immunol.19.1.423
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):1455–1458
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. https://doi.org/10.1007/s00296-013-2667-6
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):289–291
Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behçet’s disease. N Engl J Med 341(17):1284–1291. https://doi.org/10.1056/NEJM199910213411707
Scherrer MAR, Rocha VB, Garcia LC (2017) Behçet’s disease: review with emphasis on dermatological aspects. An Bras Dermatol 92(4):452–464. https://doi.org/10.1590/abd1806-4841.20177359
Suzuki N, Sakane T, Ueda Y, Tsunematsu T (1986) Abnormal B cell function in patients with Behçet’s disease. Arthritis Rheum 29(2):212–219
Tokay S, Direskeneli H, Yurdakul S et al (2001) Anticardiolipin anti-bodies in Behçet’s disease: a reassessment. Rheumatol Oxf Engl. 40(2):192–195
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. https://doi.org/10.1073/pnas.0712003105
Tursen U (2009) Activation markers in Behcet’s disease. Urkderm Arch Turk Dermatol Venerol 43:74–86
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. https://doi.org/10.3892/br.2017.996
Zhou ZY, Chen SL, Shen N, Lu Y (2012) Cytokines and Behcet’s disease. Auto-immun Rev 11(10):699–704. https://doi.org/10.1016/j.autrev.2011.12.005
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):58–61
Zouboulis CC, Büttner P, Tebbe B et al (1993) Anticardiolipin anti-bodies in Adamantiades-Behçet’s disease. Br J Dermatol 128(3):281–284
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.
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.
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).
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Djaballah-Ider, F., Djaballah, A., Djeraba, Z. et al. Auto-immunity profile evaluation during different clinical manifestations of Behçet disease in Algerian patients: effect of corticosteroid treatment. Inflammopharmacol 27, 1113–1122 (2019). https://doi.org/10.1007/s10787-019-00567-8
- Immunoglobulin isotypes