BAFF-ling autoantibodies

Abstract

There is emerging evidence that autoantibodies directed against cytokines modulate the severity of autoimmune disease. Identification of cytokine-targeted autoantibodies in patients can be informative for diagnosis and predicting clinical outcome. In this issue of the JCI, Price and colleagues used a multiplex protein microarray to identify autoantibodies in serum from SLE patients. They found autoantibodies directed against the B cell-activating factor (BAFF) were associated with greater disease severity. This study highlights the contribution of cytokine-directed autoantibodies in disease and describes a valuable tool for identifying autoantibodies against serum antigens.

Figure 1. Model for how autoantibodies against BAFF may exacerbate SLE.

Excess sBAFF promotes outgrowth of autoreactive B cells, which include BAFF-specific B cells (i). sBAFF (red) may then bind to BAFF-specific B cell receptors (BCR) on B cells and promote production of autoantibodies against BAFF (ii). BAFF-IgG immune complexes may be bound by monocyte Fc receptors (FcR), which stimulate cleavage of membrane BAFF (mBAFF; orange) and further production of sBAFF (iii). In addition, autoantibodies against BAFF may neutralize ΔBAFF (yellow), a natural regulator of BAFF (iv). Excess sBAFF may then promote autoimmunity and provide further antigen targets for BAFF-specific B cells.