Hereditary, complete deficiency of complement factor H associated with recurrent meningococcal disease.
Complement factor H (beta-1H globulin) is an important regulatory protein which inhibits the spontaneous complement activation via the alternative pathway. We describe a 15-year-old girl without any detectable factor H in plasma. She has had two episodes of meningococcal disease, but is otherwise completely healthy. Secondary to the factor-H deficiency, the levels of factor B, properdin, C3, and C5-C9 were strongly reduced due to spontaneous in vivo activation of the alternative complement pathway. Plasma C3dg was strongly elevated in spite of the factor-H deficiency; apparently erythrocyte CR1 substitutes for factor H in C3 degradation. Neither C3 nor complement lesions were demonstrable on her erythrocytes which did, however, show increased, spontaneous haemolysis in vitro in citrate plasma, but not in serum. The patient is a single child and her parents, who are unrelated and healthy, had half-normal levels of factor H. This reduction of factor H is sufficient to cause increased, spontaneous activation of the alternative pathway.
Nielsen
H E
HE
Complement Laboratory, Statens Seruminstitut, Copenhagen, Denmark.
Christensen
K C
KC
Koch
C
C
Thomsen
B S
BS
Heegaard
N H
NH
Tranum-Jensen
J
J
D000907:Antibodies, Bacterial / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood; D002648:Child; D003180:Complement C3b Inactivator Proteins / Q000172:deficiency*; D017242:Complement Factor H; D015941:Complement Hemolytic Activity Assay; D003165:Complement System Proteins / Q000172:deficiency; D003298:Coombs Test; D004912:Erythrocytes / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007122:Immunoelectrophoresis; D008589:Meningococcal Infections / Q000209:etiology*; D012008:Recurrence
D000907:Antibodies, Bacterial; D000936:Antigen-Antibody Complex; C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H; D003165:Complement System Proteins