Secondary failure of plasma therapy in factor H deficiency.
We report a patient with homozygous factor H deficiency leading to permanent alternate complement activation and early onset of the hemolytic uremic syndrome. He was successfully treated with weekly infusions of fresh frozen plasma over 4 years, displaying normal blood pressure while only treated with an angiotensin converting enzyme (ACE) inhibitor, a steady level of haptoglobin, low-range proteinuria and normal creatinine clearance. By the end of the fourth year of treatment, he dramatically developed a relapse of hemolytic and uremic syndrome, displaying undetectable haptoglobin, nephrotic range proteinuria and progressive renal failure. Despite a ten-fold increase in the dosage of plasma infusion through daily plasma exchange, haptoglobin remained undetectable while circulating antigenic factor H levels reached 22-24% (normal values 65-140%). Three months following the biological onset of the relapse, a bilateral nephrectomy was performed owing to uncontrolled hypertension and rapidly progressive renal failure. The molecular mechanism of plasma resistance remained unclear while antifactor H antibodies were not detected in the plasma. We suggest that protracted administration of exogenous factor H might not be a long-term strategy in homozygous factor H deficiency.
Nathanson
Sylvie
S
Hôpital André Mignot, 177 Rue de Versailles, 78150, Le Chesnay, France. snathanson@ch-versailles.fr
Ulinski
Tim
T
Frémeaux-Bacchi
Véronique
V
Deschênes
Georges
G
D002648:Child; D002675:Child, Preschool; D017242:Complement Factor H / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D006242:Haptoglobins / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D006720:Homozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000628:therapy*; D008297:Male; D010951:Plasma Exchange; D051437:Renal Insufficiency / Q000150:complications; D013997:Time Factors; D017211:Treatment Failure
D006242:Haptoglobins; D017242:Complement Factor H; D003404:Creatinine