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B-Cell Activating Factor (BAFF) in Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Behçet’S Disease

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B-Cell Activating Factor (BAFF) in Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Behçet’S Disease Turk J Rheumatol 2012;27(3):185-194 doi: 10.5606/tjr.2012.031 Original Article B-Cell Activating Factor (BAFF) in Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Behçet’s Disease Sistemik Lupus Eritematozus, Romatoid Artrit ve Behçet Hastalığında B Hücre Aktive Edici Faktör (BAFF) Amina Badr ELDIN,1 Safaa SAYED,2 Gehan HEGAZY,3 Olfat SHAKER4 1Department of Internal Medicine, Ain Shams University, Faculty of Medicine, Cairo, Egypt; 2Department of Rheumatology & Rehabilitation, Cairo University, Faculty of Medicine, Cairo, Egypt; 3Department of Clinical Biochemistry, King Abdulaziz University, Faculty of Medicine, Jeddah, Saudi Arabia; 4Department of Medical Biochemistry, Cairo University, Faculty of Medicine, Cairo, Egypt Objectives: This study aims to determine B-cell activating factor Amaç: Bu çalışmada romatoid artrit (RA), sistemik lupus (BAFF) serum levels in rheumatoid arthritis (RA), systemic lupus eritematozus (SLE) ve Behçet hastalığında (BH) B hücre aktive erythematosus (SLE) and Behçet's disease (BD) and correlate edici faktör (BAFF) serum düzeyleri ve bu düzeylerin hastalık these levels with disease activity and severity. aktivitesi ve şiddeti ile olan ilişkisi araştırıldı. Patients and methods: Between December 2010 and December Hastalar ve yöntemler: Aralık 2010 - Aralık 2011 tarihleri 2011, 63 Egyptian patients with collagen diseases [RA (n=21), arasında, Kahire ve Ain Shaims Üniversite Hastanelerinden SLE (n=21); BD (n=21)] were recruited from Cairo and Ain Shams kolajen hastalığı olan 63 Mısırlı hasta [RA (n=21), SLE (n=21), University Hospitals, along with 21 apparently healthy individuals BH (n=21)] ve beraberinde görünüşü sağlıklı olan 21 kişi kontrol as controls. All participants underwent history taking, clinical grubu olarak çalışmaya dahil edildi. Katılımcıların tümünün examination, laboratory and radiological investigations, and öyküsü alındı, klinik muayenesi ve laboratuvar ve radyolojik disease activity score estimation. The serum BAFF level was incelemeleri yapıldı ve hastalık aktivite skoru hesaplandı. Serum measured by an enzyme-linked immunosorbent assay (ELISA) BAFF düzeyi, enzim bağlı immünosorbent assay (ELISA) kiti ile kit. ölçüldü. Results: The BAFF serum levels were significantly elevated in Bulgular: BAFF serum düzeyleri, sağlıklı kontrollere kıyasla patients with SLE and BD versus the healthy controls (p<0.011, SLE ve BH hastalarında (p<0.011, p<0.023) ve RA ve BH’ye p<0.023) and in SLE versus RA and BD (p<0.024, p<0.026). kıyasla SLE hastalarında (p<0.024, p<0.026) anlamlı düzeyde A significant positive correlation was found between the BAFF daha yüksekti. Romatoid artritte BAFF ve C-reaktif protein and C-reactive protein (CRP) (r=0.928, p<0.0001), the Disease (CRP) (r=0.928, p<0.0001), Hastalık Aktivite Skoru 28 (DAS28) Activity Score 28 (DAS28) (r=0.810, p<0.0001), and disease (r=0.810, p<0.0001) ve hastalık kontrolü arasında (r=0.834, control (r=0.834, p<0.0001) in RA. Also, a significant positive p<0.0001) anlamlı bir pozitif ilişki saptandı. Ayrıca SLE’de BAFF correlation was found between BAFF and SLE Disease Activity ve SLE Hastalık Aktivite İndeksi (SLEDAI) skor sınıflandırması Index (SLEDAI) score classification (r=0.894, p<0.0001) and (r=0.894, p<0.0001) ve SLEDAI skoru arasında (r=0.748, SLEDAI score (r=0.748, p<0.0001) in SLE as well as between the p<0.0001) ve BH’de BAFF ve hastalık süresi arasında da BAFF and disease duration (r=0.578, p<0.006) in BD. (r=0.578, p<0.006) anlamlı bir pozitif ilişki saptandı. Conclusion: The BAFF serum levels are increased in patients Sonuç: Kontrol grubuna kıyasla, SLE ve BH hastalarında with SLE and BD versus the controls and in patients with SLE ve RA ve BH hastalarına kıyasla SLE hastalarında BAFF compared with those with RA and BD. They also have a positive serum düzeyleri yüksektir. Ayrıca SLE ve RA’da, BAFF’nin bu correlation with disease severity in SLE and RA, which suggests hastalıkların patogenezi ve aktivitesinde rol oynayabileceğini that BAFF may play a role in the pathogenesis and activity of gösterebilen, hastalık şiddeti açısından pozitif bir ilişki these diseases. These results may pose the possibility that de mevcuttur. Bu bulgular, selektif olarak BAFF biyolojik a human monoclonal antibody drug which selectively inhibits aktivitesini inhibe eden insan monoklonal antikor ilacının, aktif BAFF biological activity may be useful in the treatment of active dirençli olguların tedavisinde faydalı olabilme olasılığını akla resistant cases. getirmektedir. Key words: Behçet's disease; disease activity; rheumatoid arthritis; serum Anahtar sözcükler: Behçet hastalığı; hastalık aktivitesi; romatoid artrit; B-cell activating factor; systemic lupus erythematosus. serum B hücre aktive edici faktör; sistemik lupus eritematozus. Received: January 30, 2012 Accepted: June 27, 2012 Correspondence: Gehan Hegazy, M.D. Department of Clinical Biochemistry, King Abdulaziz University, Faculty of Medicine, Jeddah, Saudi Arabia. Tel: 00966542843217 e-mail: [email protected] ©2012 Turkish League Against Rheumatism. All rights reserved. 186 Turk J Rheumatol B cells are not only involved in the production of that may be directly involved in joint damage. It is antibodies, but also serve as antigen-presenting cells well known that B cells are critical in the activation which co-regulate T cell activation through cytokine of CD4+ T cells.[12] production.[1] The B-cell activating factor (BAFF) is Behçet’s disease (BD) is a complex multisystem a key cog in the survival of B cells and ensures their vasculitis of unknown etiology. In this disease, existence through reducing apoptotic clearance.[2] It four major symptoms are evident: recurrent oral belongs to the tumor necrosis factor (TNF) ligand aphthous ulcers, skin lesions, ocular lesions, and super family[3] and consists of a transmembrane genital ulcers. In addition, minor symptoms such protein, from which a biologically active soluble 27 kD as articular manifestations, involvement of the protein is cleaved.[4] The BAFF is produced by myeloid digestive tract, epididymitis, vascular involvement, lineage cells, malignant B cells, activated T cells, and [5] and neuropsychiatric symptoms can also be found. bone marrow stromal cells and has three receptors In BD, venous involvement is common, whereas that belong to the TNF receptor superfamily: the B arterial involvement is rare.[13] It is recognized that cell maturation antigen (BCMA), the transmembrane atherothrombosis in systemic inflammatory disorders activator, calcium-modulator and cyclophilin ligand [6] is closely related to abnormalities associated with interactor (TACI), and the BAFF receptor (BAFF-R). coagulation and lipid metabolism.[14] The precise These receptors are primarily expressed in B cells, but mechanisms of tissue destruction in BD have not been TACI and BAFF-R are known to be expressed by T cell [7] fully elucidated. Nevertheless, a growing number of subsets as well. Because of the receptor distribution, reports have involved the investigation of T and B the studies on the BAFF have focused on B cells and T lymphocyte-mediated immune responses.[15] Recently, cells. It has been shown that the BAFF is responsible [8] resistant cases of retinal vasculitis due to BD have for B cell survival and maturation, and it is essential been treated successfully with rituximab, a chimeric, for the development of B cell tolerance. A breakdown monoclonal antibody that acts against the specific B of the regulation of the BAFF expression results in cell antigen, CD20. The recent success of rituximab in excessive production that impairs B cell tolerance and cases of autoimmune diseases which are considered to leads to autoimmune phenomena.[9] The BAFF also [10] be T cell-mediated, like BD, indicates that B cells must functions as a T cell co-stimulatory molecule. have a much broader role in the pathogenesis of this Systemic lupus erythematosus (SLE) is a disease than has been previously thought.[16] complicated autoimmune disease. Although self- The aim of this study was to determine and compare reactive B cells produce the autoantibodies essential the serum level of the BAFF in patients with RA, SLE, for the diagnosis of the disease, B cells have and BD and also to correlate its serum level with proven in recent years to be active participants disease activity indices and severity. in the development of this disease irrespective of autoantibody production. In light of this PATIENTS AND METHODS advancement, a central question surrounding the pathogenesis of the disease is whether intrinsic This retrospective study included 63 Egyptian patients defects in SLE B cells play a role in triggering the with collagen diseases from outpatient clinics of the immunological events that result in the onset of Internal Medicine and Rheumatology Departments clinical disease. Although other immune cells play of Cairo and Ain Shams University Hospitals between a role in SLE, B cells from SLE patients display December 2010 and December 2011 as well as 21 apparently healthy individuals who were either on the signaling defects that may underlie the pathogenesis medical staff or were patient’s relatives that served and explain the characteristic hyperactivity of as the healthy controls. The study was conducted B cells in active disease.[11] The classic paradigm according to the principles of the Helsinki Declaration for rheumatoid arthritis (RA) pathogenesis holds and was approved by the local ethics committee of the that CD4+ T cells mediate joint damage both
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