Rare Immune Dysregulatory Disorder Leading to Lung Transplantation

Abstract

<h3>Introduction</h3> Interleukin-12 receptor β1 is a common receptor chain of the pro-inflammatory cytokines IL-12 and -23. IL-12/IL-23Rβ1 deficiency is a rare autosomal recessive disorder characterized by predisposition to mycobacteria infections, whereas IL-12/IL-23Rβ1 gain-of-function mutation may cause a systemic disease that manifests as a chronic inflammatory condition and organ fibrosis. We describe the first case of lung transplantation (LTx) in lung-fibrosis due to this immune dysregulatory disorder. <h3>Case Report</h3> We present a 27-year-old patient diagnosed with gain-of-function mutation in IL-12/IL-23Rβ1. The disorder led to multi-organ involvement consisting of interstitial lung disease with secondary pulmonary hypertension, hepatitis, dermatosis and hepatosplenomegaly. Multiple immunosuppressive and modulating agents were tried without improving lung function. The patient showed no susceptibility to infections. With increasing pulmonary hypertension and progressive respiratory failure, he reached indication for LTx. Prior to listing, concerns were raised due to his exceptional pro-inflammatory immunodeficiency and potentially increased risk of rejection. After extended research and with few other treatment options left, LTx was performed in 2017 (ABO-compatible and negative crossmatch) with an uncomplicated perioperative course. He received standard immunosuppression with the goal of high cyclosporine level within standard target range. In his first year post-transplant he was treated 3 times successfully for minimal acute rejection and has since then had no further rejections. In 2018 he developed Candida dubliensis sepsis and osteomyelitis and was treated for 16 months. A pan-JAK-inhibitor was initiated, while mycophenolate was reduced and stopped, to try to inhibit a progressive sterile liver and bone inflammation. The regimen had remarkable effect on the patient`s general condition. Recurring CMV reactivation ensued and in 2020 also systemic Mycobacterium avium intracellulare infection, still requiring treatment. Pulmonary function is stable. <h3>Summary</h3> Our experience suggests that LTx is a valid option for this indication resulting in much improved quality of life. It remains challenging to find the right balance between treating the underlying disease while providing adequate immunosuppression to prevent rejection and avoiding infections.