Complement inhibition in post-transplant IgA-mediated autoimmune cytopenia: A pediatric case report Free

Background: Autoimmune hemolytic anemia (AIHA) is a well-described complication in pediatric populations and solid organ transplant recipients. AIHA post-transplant is most frequently reported after heart or lung transplants, where lymphoid tissue transfer is highest. While autoimmune clearance is typically IgG-mediated, a rare form of IgA-mediated cold agglutinin disease can present diagnostic and therapeutic challenges. Standard treatment for post solid organ transplant autoimmunity has historically targeted suppression of humoral and cellular immunity with corticosteroids and rituximab but complement inhibition has emerged as a promising strategy in refractory cases. ¹⁻⁴ We present the novel application of C5 inhibition to suppress severe IgA mediated cold agglutinin red blood cell hemolysis and thrombocytopenia.

Case Presentation: We present a 9-year-old male with a history of heart transplantation in infancy (June 2015) for hypoplastic left heart syndrome. He developed cellular rejection one-year post-transplant and was treated with cyclosporine and MMF. At 7 years post-transplantation, he developed acute cellular rejection with third-degree heart block requiring pulse steroids and ATG, with subsequent transition to tacrolimus/sirolimus.

2 years after the change in his immunosuppresion, he presented with symptomatic anemia (Hgb 5.5 g/dL), thrombocytopenia (Plt 32,000/µL), and reticulocytosis (9.6%). Complement levels were normal. Direct antiglobulin testing was negative; however, “super Coombs” revealed weakly positive IgA antibodies. Initial therapy with prednisone and rituximab yielded minimal response.

Due to persistent anemia, he was initiated on eculizumab (a C5 inhibitor) with continued slow prednisone wean. This resulted in significant hematologic improvement. He has since successfully weaned off prednisone and we are currently trying to wean eculizumab. He is maintaining stable hemoglobin 11-12 g/dL.

Discussion: This case underscores the importance of considering IgA-mediated AIHA in post-transplant patients with Coombs-negative hemolysis and/or thrombocytopenia. Modification of immunosuppression is particularly challenging in the post solid organ transplant setting and can risk organ rejection requiring close collaboration with primary transplant team.⁵⁻⁶ In IgA-driven diseases like IgA nephropathy, complement inhibitors (e.g., eculizumab, narsoplimab) are gaining traction.⁷ This case adds to emerging evidence that complement modulation is a viable treatment pathway for refractory IgA-mediated AIHA, especially in the post-transplant setting.Conclusion: Eculizumab with prednisone was effective and well-tolerated in this case of IgA-mediated, rituximab-refractory AIHA post-heart transplant. Complement inhibition may represent a novel and safe therapeutic approach in similar clinical contexts and warrants further investigation.