Anti-complement factor H (CFH) antibodies and a novel CFH gene mutation in an atypical hemolytic uremic syndrome patient with complement activation of the classical pathway.

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by overactivation of the complement alternative pathway. aHUS involves the presence of antibodies against complement factor H and its mutations in the complement genes. A 2-month-old boy presented with discoid rash, hemolytic anemia, thrombocytopenia, multiple antibodies, and hypocomplementemia with a very low level of C4 (< 3\u2009mg/dL), indicating activation of the complement pathway, together fulfilling the systemic lupus erythematosus (SLE) criteria of the American College of Rheumatology at 5\u2009months of age. However, most of these findings normalized spontaneously without any intervention. Further investigations revealed a high level of anti-complement factor H antibodies and a novel heterozygous missense mutation (p.Glu1172Ala, located in exon 22) in a complement gene, CFH. At 2\u2009years of age, his SLE-like symptoms have not recurred, but hematuria and schistocytes were persistent. Eventually, aHUS was diagnosed rather than SLE. Our findings suggest that multiple antibody complex, including anti-complement factor H antibody, may temporarily activate the classical pathway, resulting in SLE-like findings.