PURPOSE: Belimumab is a humanized IgG1 monoclonal antibody to B-cell activating factor (BAFF), also known as B-lymphocyte Stimulator (BLyS). BAFF works through three receptors to enhance B-cell and plasma cell survival and growth.

We hypothesize that blocking BAFF activity will be a useful therapy for antibody mediated rejection.

METHODS: A kidney-pancreas transplant recipient developed cellular and vascular rejection of her kidney allograft associated with high levels of HLA-DR53 antibodies. Steroids and ATG resolved the cellular component of her rejection but even after several cycles of antibody depleting therapy with pheresis, IVIG and rituximab, kidney allograft inflammation persisted and HLA-DR53 antibody titers remained high. Treatment with belimumab was initiated with 120mg for the first dose and then 400mg every two weeks thereafter.

RESULTS: Serum creatinine, which had been 4.0-4.5 mg/dl prior to therapy, decreased to 2.8 mg/dl and HLA-DR53 antibody MFIs decreased by 30% after the first dose of belimumab. Therapy was well tolerated. Oral acetaminophen and diphenhydramine were used for pre-medication.

CONCLUSION: Belimumab may be an effective therapy for antibody-mediated rejection. It is not clear if therapy will need to be continuous, but is so, periodic injections are well tolerated. Assessing expression of BAFF receptors within transplant allografts is underway and may be useful for predicting responders to belimumab.

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