Successful Eradication of De Novo C1q-Binding Donor-Specific Antibodies with Rituximab Monotherapy

Abstract

<h3>Introduction</h3> Antibody-mediated rejection (AMR) is an increasingly recognized cause of lung transplant allograft failure. Treatment of AMR involves combination therapy that is often poorly tolerated or unsuccessful with regimens involving the combination of intravenous immunoglobulins, plasmapheresis, and proteasome inhibitors, complement, or CD20 therapy. The development of DSAs alone, specifically complement activating C1q-binding DSAs, has been identified as an independent risk factor for solid organ transplant allograft dysfunction. Previous studies have examined the efficacy of combination therapy involving the anti-CD20 antibody rituximab to preemptively eliminate DSAs. Here we report on a case of successful eradication of de novo C1q-binding DSAs in a lung transplant recipient using rituximab. <h3>Case Report</h3> Our patient underwent double-lung transplantation for idiopathic pulmonary fibrosis in August 2019. His post-transplant course was notable for multiple episodes of acute cellular rejection (ACR) requiring burst-dose corticosteroids. DSA titers were monitored every three months post-transplant. At six months, de novo DSAs were detected (DQ7 with DQA1*05) at a mean fluorescence intensity (MFI) of 3623 (low-moderate) (Figure 1). These subsequently rose to an MFI of 11281 (strong) with development of C1q positivity that peaked at an MFI of 15038. Given his frequent episodes of ACR, the strong C1q positivity, and concerns regarding his ability to tolerate therapy for potential future AMR, he was preemptively treated with a single infusion of rituximab (375 mg per meter-squared body surface area). Follow-up DSA titers demonstrated near-total elimination of the C1q component (MFI 403). The patient tolerated the treatment without issue and continues to demonstrate improvement in his allograft function. <h3>Summary</h3> Rituximab monotherapy can be considered preemptively in patients with C1q-binding DSAs that may not tolerate traditional treatment of antibody-mediated rejection.