Complement 2 deficiency

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disorder resulting in a broad spectrum of manifestations in several organs, mainly skin and kidney. SLE occurs with interaction of genetic and environmental factors. The most remarkable genetic predisposition to SLE is deficiency of early components of the classical complement pathway. A five-year-old, previously healthy female patient was admitted to our hospital with headache, fever, focal partial seizure, diagnosed and treated as encephalitis. She was re-admitted to our hospital at six years of age with fever, fatigue, alopecia and oral aphthous ulcers and necrotizing vasculitis on extremities. Significant hypocomplementemia, anemia, proteinuria and positive autoantibodies and coombs test led to the diagnosis of SLE. Due to early disease onset and distinct autoimmune manifestations, we diagnosed our patient with type I complement 2 (C2) deficiency with a frameshift mutation in C2 gene and a serum C2 level of <0.2 mg/dL. To our knowledge, this is the first case of genetically confirmed and successfully treated hereditary C2 deficient SLE patient diagnosed with necrotizing vasculitis. We wish to highlight that distinctive autoimmune manifestations should guide physicians to research on monogenic lupus, particularly C2 deficiency, even in the absence of coexisting recurrent pyogenic infections.

Abstract: C2 deficiency (C2D) is the most common homozygous complement deficiency, leading to susceptibility to recurrent pyogenic infections with encapsulated bacteria due to defective opsonization and complement activation. Typical bacteria associated with these infections are Streptococcus pneumonia, Haemophilus influenza type b, and Neisseria meningitides. Pseudomonas aeruginosa is not a typical encapsulated bacterium, although reports have indicated that it can activate the complement system. Here we report an infant with Pseudomonas aeruginosa bacteremia who was diagnosed subsequently with C2D Type I. The patient was a 10-month-old male with no significant past medical history who presented to an outside hospital with twoday history of vomiting, diarrhea and fever. Because of his progressive illness, he was admitted to the hospital for infectious evaluation. His blood culture grew Pseudomonas aeruginosa within 24 hours, while urine and CSF cultures were negative. He was treated with ceftazidime without any complications and was sent home. He was subsequently admitted to our hospital because of persistent diarrhea and dehydration. An immunodeficiency evaluation was performed because of his history of Pseudomonas bacteremia. The results were remarkable for undetectable CH50 and C2 levels. Genetic testing revealed homozygous for C2D Type I. This is the first reported case of C2D presenting with Pseudomonas aeruginosa bacteremia. This case illustrates the potential importance of C2 in protecting from opportunistic bacteria such as Pseudomonas. Complement deficiency should be on the differential diagnosis of infants with Pseudomonas bacteremia.