ABSTRACT
A carrier of chronic granulomatous disease (CGD) has had recurrent severe purulent infections like those characteristic of CGD. The carrier state was demonstrated by the presence of both normal and CGD granulocytes in her blood; the percentage of normal granulocytes varied from 4% to 44% over 4 years. In addition, her granulocytes were partially defective in killing Escherichia coli and staphylococci and in the release of superoxide anion during stimulation. Extensive evaluation of her immune system and phagocyte function failed to reveal a second abnormality. The course in this child indicates that the carrier state for X-linked CGD cannot be considered a benign condition and might be more properly conceptualized as a continuum in expression of the full disease. Screening assays for CGD should possess the capacity to diagnose carriers of the X-linked form of the disease.
Subject(s)
Granulomatous Disease, Chronic/genetics , Infections/etiology , Mosaicism , Blood Bactericidal Activity , Child , Female , Granulomatous Disease, Chronic/blood , Granulomatous Disease, Chronic/immunology , Heterozygote , Humans , Phagocytosis , RecurrenceSubject(s)
Complement C2/deficiency , Suppuration/etiology , Adolescent , Complement Pathway, Alternative , Female , Humans , InfantABSTRACT
Patients with sickle cell disease and individuals who have undergone splenectomy share defects of certain host defense mechanisms and a predisposition to severe pyogenic bacterial infections. Since patients with sickle cell disease can have deficient activity of the alternative complement pathway, we have tested such activity in sera from splenectomized children and adults. A new kinetic hemolytic assay has been used, and we have compared results to those obtained with sera from patients with sickle cell disease or hypogammaglobulinemia. Sera from six of 58 splenectomized individuals (10%) had defective function of the alternative pathway, compared to 10 of 62 sera from patients with sickle cell disease (16%) and 10 of 18 sera from hypogammaglobulinemic patients (56%). Deficiency of antibody, a rate-influencing component of alternative pathway activity in this system, appears responsible for deficient activity in the hypogammaglobulinemic sera. The molecular basis for the deficiency found in sickle cell disease or after splenectomy is not clear. Defective function of the alternative complement pathway could contribute to the increased predisposition to bacterial infection that exists in these three patient groups.
Subject(s)
Agammaglobulinemia/immunology , Anemia, Sickle Cell/immunology , Complement Activation , Complement Pathway, Alternative , Splenectomy , Adolescent , Adult , Agammaglobulinemia/therapy , Anemia, Sickle Cell/therapy , Child , Child, Preschool , Complement C3/analysis , Female , Humans , Immunoglobulins/analysis , Immunologic Techniques , Infant , Male , Middle Aged , Purpura, Thrombocytopenic/immunology , Spherocytosis, Hereditary/immunologyABSTRACT
NADPH oxidase activity was examined in paired 27,000 x g granule fractions isolated from normal polymorphonuclear leukocytes from patients with chronic granulomatous disease. At 0.17 mM NADPH, the oxidase activity was not measurable in normal resting cells but was activated by phagocytosis. This activation was absent in CGD cells. At higher levels of NADPH, activity was present in cells from patients with CGD, although it was lower than normal, and no difference in activity was found between resting and phagocytizing cells. Granule fractions from phagocytizing normal cells exhibited higher than granule fractions from resting normal cells at all levels of NADPH. These results suggest that NADPH oxidase activity is defective in chronic granulomatous disease, and further that the defect is not the absence of the enzyme but rather a failure to activate it.
Subject(s)
Granulomatous Disease, Chronic/enzymology , NADH, NADPH Oxidoreductases/deficiency , Neutrophils/enzymology , Phagocyte Bactericidal Dysfunction/enzymology , Adolescent , Adult , Child , Child, Preschool , Enzyme Activation , Female , Genes, Recessive , Granulomatous Disease, Chronic/genetics , Humans , Infant , Male , NADP , Osmolar Concentration , Phagocytosis , Sex ChromosomesSubject(s)
Complement System Proteins/physiology , Infections/immunology , Adolescent , Anemia, Sickle Cell/immunology , C-Reactive Protein/physiology , Child, Preschool , Complement System Proteins/metabolism , Enzyme Activation , Female , Humans , Immunity, Cellular , Immunologic Deficiency Syndromes/congenital , Infant, Newborn , Lipopolysaccharides/physiology , Lupus Erythematosus, Systemic/immunology , Male , Properdin/metabolism , Properdin/physiology , Virus Diseases/immunologyABSTRACT
Bacterial infections are the most frequent cause of death and an important factor of morbidity in sickle cell disease. A defect in oxidative metabolism of neutrophils from these patients has been reported as a possible cause for these infections. Since normal neutrophil functions are essential in the defense against bacteria, it seemed important to reassess the capacity of neutrophils from patients with sickle cell disease to undergo the metabolic events associated with phagocytic bactericidal activity. Accordingly, neutrophils from patients and controls were compared for their ability to reduce nitroblue tetrazolium dye, to activate the hexose monophosphate shunt, and to generate superoxide anion, hydrogen peroxide, and chemiluminescence. Patients' cells performed normally in each of these assays and, in addition, killed Staphylococcus aureus as well as did cells from controls. Thus, an abnormality of neutrophil oxidative metabolism cannot explain the propensity to bacterial infections in sickle cell disease.