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BAFF // B Cell Activating Factor

Biomarker Therapeutic Areas: 
Biomarker Matrices: 

B-cell Activating Factor (BAFF) is a member of the TNF family and induces B cell proliferation and differentiation. The soluble form of BAFF is a 152aa with a single disulfide bond (Moore et al., 1999).

This cytokine is also called tumor necrosis factor ligand superfamily member 13b (TNFSF13b), B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) among other names.

BAFF binds to 3 receptors: TACI, BCMA and BAFF-R/BR-3. The third one binds only BAFF but the two others also bind APRIL (A PRoliferation Inducing Ligand from the TNF family ligand)(Wei et al.2015). BAFF is one of the major factors implicated in the maturation and survival of B cells (Cancro, 2004). Mice overexpressing BAFF develop autoimmune manifestations (autoantibodies, germinal center formation…)(Mackay et al., 1999). Elevated BAFF levels are found in patient with several autoimmune diseases (Fabris et al., 2010; Moura et al., 2011; Toubi et al., 2006)

BAFF levels have also been found to decrease in Sjögren’s syndrome and juvenile idiopathic arthritis under different therapeutics (Glaesener et al., 2014; Pollard et al., 2013; St Clair et al., 2013)

 

BAFF assay is a solid phase enzyme linked immunoassay which has been validated in the laboratory for measurement in human serum.

 

Cancro, M.P. (2004). The BLyS family of ligands and receptors: an archetype for niche-specific homeostatic regulation. Immunol. Rev. 202, 237–249.

Fabris, M., Grimaldi, F., Villalta, D., Picierno, A., Fabro, C., Bolzan, M., De Vita, S., and Tonutti, E. (2010). BLyS and April serum levels in patients with autoimmune thyroid diseases. Autoimmun. Rev. 9, 165–169.

Glaesener, S., Quách, T.D., Onken, N., Weller-Heinemann, F., Dressler, F., Huppertz, H.-I., Thon, A., and Meyer-Bahlburg, A. (2014). Distinct Effects of Methotrexate and Etanercept on the B Cell Compartment in Patients With Juvenile Idiopathic Arthritis. Arthritis Rheumatol. Hoboken Nj 66, 2590–2600.

Mackay, F., Woodcock, S.A., Lawton, P., Ambrose, C., Baetscher, M., Schneider, P., Tschopp, J., and Browning, J.L. (1999). Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations. J. Exp. Med. 190, 1697–1710.

Moore, P.A., Belvedere, O., Orr, A., Pieri, K., LaFleur, D.W., Feng, P., Soppet, D., Charters, M., Gentz, R., Parmelee, D., et al. (1999). BLyS: Member of the Tumor Necrosis Factor Family and B Lymphocyte Stimulator. Science 285, 260–263.

Moura, R.A., Cascao, R., Perpetuo, I., Canhao, H., Vieira-Sousa, E., Mourao, A.F., Rodrigues, A.M., Polido-Pereira, J., Queiroz, M.V., Rosario, H.S., et al. (2011). Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival. Rheumatology 50, 278–282.

Pollard, R.P.E., Abdulahad, W.H., Vissink, A., Hamza, N., Burgerhof, J.G.M., Meijer, J.M., Visser, A., Huitema, M.G., Spijkervet, F.K.L., Kallenberg, C.G.M., et al. (2013). Serum levels of BAFF, but not APRIL, are increased after rituximab treatment in patients with primary Sjögren’s syndrome: data from a placebo-controlled clinical trial. Ann. Rheum. Dis. 72, 146–148.

St Clair, E.W., Levesque, M.C., Luning Prak, E.T., Vivino, F.B., Alappatt, C.J., Spychala, M.E., Wedgwood, J., McNamara, J., Moser Sivils, K.L., Fisher, L., et al. (2013a). Rituximab Therapy for Primary Sjögren’s Syndrome: An Open-Label Clinical Trial and Mechanistic Analysis. Arthritis Rheum. 65, 1097–1106.

Toubi, E., Gordon, S., Kessel, A., Rosner, I., Rozenbaum, M., Shoenfeld, Y., and Zuckerman, E. (2006). Elevated serum B-Lymphocyte activating factor (BAFF) in chronic hepatitis C virus infection: Association with autoimmunity. J. Autoimmun. 27, 134–139.

Wei, F., Chang, Y., and Wei, W.(2015) The role of BAFF in the progression of rheumatoid arthritis. Cytokine.

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