M.P.C. Florido

Inherited Complete Factor I Deficiency Associated with Systemic Lupus Erythematosus, Higher Susceptibility to Infection and Low Levels of Factor H

Here we describe two new cases of complete deficiency of factor I (fI) in two sisters from a consanguineous Brazilian family. The eldest sibling (20‐year‐old) developed systemic lupus erythematosus (SLE) early during childhood while the youngest had been committed on several occasions owing to repeated infections although she was asymptomatic for auto‐immune diseases. We also detected lower concentrations of C3 and factor B in both sisters. Biological functions dependent on complement activation such as the production of opsonins and killing of phagocytozed micro‐organisms, chemotactic factors and haemolytic activity were all significantly reduced in both probands. Consistent with the absence of fI and low levels of fH, a deregulated production of C3b was observed by bidimensional electrophoresis in sera of both the probands.

Is immunity in diabetic patients influencing the susceptibility to infections? Immunoglobulins, complement and phagocytic function in children and adolescents with type 1 diabetes mellitus

Abstract:  Objective:  Previous reports suggest an increased susceptibility of diabetes patients to infections, but little information is available on possible underlying immunologic dysfunctions. The aim of this study was to evaluate humoral factors in pediatric patients with type 1 diabetes mellitus.

Hereditary Human Complement C3 Deficiency Owing to Reduced Levels of C3 mRNA

An 8‐year‐old son (L.A.S.) of consanguineous parents, presented recurrent bacterial infections, vasculitis and extremely low levels of serum C3 (0.15 µg/ml). The classical and alternative pathway haemolytic activities and the generation of opsonins and chemotactic factors derived from the activation of the complement system were markedly affected in the probands serum. An in vitro addition of purified C3 restored the classical pathway‐dependent haemolytic activity of his serum. Autoradiographs of the probands lipopolysaccharide (LPS)‐stimulated and 35S‐labelled fibroblast supernatants after that the SDS‐PAGE revealed no C3 α or β chains. The amount of C3 mRNA synthesized by the probands fibroblasts, as evaluated by reverse transcription–polymerase chain reaction (RT–PCR) assays, was greatly reduced.

Deficiency of the Human Complement Regulatory Protein Factor H Associated with Low Levels of Component C9

We identified a 4‐year‐old Brazilian boy from a family of Japanese descent and history of consanguinity, who suffered from severe recurrent pneumonia. He carries factor H (FH) deficiency associated with reduced levels of component C9 and low serum levels of C3 and factor B. His mother also presented low levels of these proteins and factor I, while his father and sister had only lower levels of FH. Western blot assays confirmed the complete absence of FH and FHL‐1 polypeptides in this patient. Sequencing of the proband’s FH cDNA revealed a homozygous G453A substitution, encoding an Arg127His change. His mother, father and sister are heterozygous for this substitution. Despite the absence of FH in the plasma, this protein was detected in the patient’s fibroblasts, suggesting that Arg127 may be important for FH secretion. Low concentrations of C9 were detected in the proband serum but no mutations in the patient’s C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption.