Primary Amoebic Meningoencephalitis caused by Complement C2 Deficiency.

Background: Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and often fatal central nervous system infection caused by Methods: We conducted comprehensive clinical, immunological, and genetic investigations in one of the few survivors of PAM. We performed high-dimensional immune profiling using Cytometry by Time-Of-Flight (CyTOF) to assess immune cell composition and activation state. We employed whole-exome sequencing (WES) to identify rare genetic variants that affect host responses. Functional immune assays were used to assess serum-mediated amoebicidal activity Results: A previously healthy pediatric patient was diagnosed with PAM. Contrary to other cases, her clinical course lasted for more than 2 months before she recovered with miltefosine treatment. Immunologic evaluation showed this patient had normal numbers and frequencies of major lymphoid and myeloid immune cells. WES revealed a homozygous deletion in the complement component 2 (C2) gene, resulting in a complete absence of circulating C2 protein and abolishing classical complement pathway activity. Normal human serum induced complement-mediated lysis of Conclusion: Our study demonstrates that PAM can be caused by a monogenic inborn error of immunity (IEI) and that the complement system is critical for human immunity against