Hereditary angioneurotic laryngeal edema (HALE) is an autosomal dominant hereditary disease in which there is a decrease or defect in the C1 inhibitor (C1-INH). The pathophysiology of HALE is characterized by recurrent spontaneous episodes of transient edema of the laryngeal mucose and submucosal tissue with remission at irregular. Patients may die because of a life-threatening acute upper airway obstruction caused by laryngeal edema. HALE was diagnosed on the clinical symptoms, family history, and markedly decreased serum C1-INH activity and C1-INH protein.
Angioedemas, Hereditary ; diagnosis ; Complement C1 Inactivator Proteins ; analysis ; metabolism ; Complement C1 Inhibitor Protein ; Humans ; Laryngeal Edema ; diagnosis ; Recurrence

OBJECTIVETo identify the mutation of C1 inhibitor (C1 INH) gene in a Chinese family with hereditary angioedema (HAE).

METHODSPolymerase chain reaction and direct sequencing were used to identify the mutation type. The sequencing results were compared with the normal sequences in GenBank to find the mutation. In order to exclude the polymorphism, 30 normal volunteers were analyzed.

RESULTSOne novel mutation (17839 del C) was detected in 5 patients with HAE. The mutation was not found in controls.

CONCLUSIONThe mutation of C1 INH gene (17839 del C) is identified in the family. Molecular diagnosis can be made by detecting the mutation.

Angioedema ; genetics ; Chromosomes, Human, Pair 11 ; genetics ; Complement C1 ; genetics ; Complement C1 Inactivator Proteins ; genetics ; Exons ; Family Health ; Female ; Humans ; Male ; Pedigree ; Point Mutation ; Sequence Deletion

INTRODUCTIONWe report angioedema as a rare presentation leading to a diagnosis of systemic lupus erythematosus (SLE).

CLINICAL PICTUREA diagnosis of angioedema was delayed in a patient presenting with limb and facial swelling until she developed acute upper airway compromise. After excluding allergic and hereditary angioedema, acquired angioedema (AAE) was suspected, possibly precipitated by respiratory tract infection. Associated clinical and laboratory features led to a diagnosis of SLE.

TREATMENTManagement proved challenging and included high dose steroids and immunosuppressants.

OUTCOMEThe patient responded to treatment and remains in remission without recurrence of the angioedema.

CONCLUSIONAAE occurs due to the acquired deficiency of inhibitor of C1 component of complement (C1 INH). Lymphoproliferative disorders and anti-C1 INH antibodies are well-described associations. However, one should also consider the possibility of SLE.

Angioedema ; blood ; etiology ; physiopathology ; therapy ; Antiphospholipid Syndrome ; diagnosis ; etiology ; Brain ; pathology ; Complement C1 Inactivator Proteins ; analysis ; deficiency ; Female ; Humans ; Lupus Erythematosus, Systemic ; complications ; diagnosis ; etiology ; Magnetic Resonance Imaging ; Middle Aged ; Respiration, Artificial ; Respiratory Insufficiency ; etiology ; therapy

OBJECTIVETo explore the characteristics in CFHR1 concentration and the frequency of CFHR1 gene polymorphisms of patients with type 2 diabetes mellitus (T2DM) based on the high level of complement factor H (CFH) expression among such patients and the similarity between CFHR1 and CFH in terms of sequence and functions.

METHODSFifty T2DM patients and 30 healthy controls were selected. The plasma samples were separated by pI with OFFGEL electrophoresis following solution digestion. Further separation and identification were carried out on a Nano HPLC-Chip-MS/MS system. Differentially expressed proteins were identified by comparison. Enzyme-linked immunosorbent assay (ELISA) was used to validate the result. Genomic DNA of the two groups was extracted. Polymerase chain reaction and sequencing were used to determine the single nucleotide polymorphisms in the 6 exons of the CFHR1 gene.

RESULTSThe CFHR1 level in plasma of T2DM patients were significantly higher than that of the healthy controls (P=2.78× 10). A significant difference in allelic frequencies of rs12406079 of the fifth exon of the CFHR1 gene was found between the two groups (χ=5.692, P=0.017).

CONCLUSIONThe concentration of CFHR1 and frequencies of CFHR1 gene polymorphisms among patients with T2DM differ significantly from healthy subjects. Polymorphisms of the CFHR1 gene are associated with T2DM.

Complement C3b Inactivator Proteins ; genetics ; metabolism ; Diabetes Mellitus, Type 2 ; genetics ; metabolism ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

Antibodies, Monoclonal, Humanized ; therapeutic use ; Complement Inactivator Proteins ; therapeutic use ; Hemoglobinuria, Paroxysmal ; therapy ; Humans

Proteins of the complement system are known to interact with many charged substances. We recently characterized binding of C1q and factor H to immobilized and liposomal anionic phospholipids. Factor H inhibited C1q binding to anionic phospholipids, suggesting a role for factor H in regulating activation of the complement classical pathway by anionic phospholipids. To extend this finding, we examined interactions of C1q and factor H with lipid A, a well-characterized activator of the classical pathway. We report that C1q and factor H both bind to immobilized lipid A, lipid A liposomes and intact Escherichia coli TG1. Factor H competes with C1q for binding to these targets. Furthermore, increasing the factor H: C1q molar ratio in serum diminished C4b fixation, indicating that factor H diminishes classical pathway activation. The recombinant forms of the Cterminal, globular heads of C1q A, B and C chains bound to lipid A and E. coli in a manner qualitatively similar to native C1q, confirming that C1q interacts with these targets via its globular head region. These observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain targets. This is distinct from its role as an alternative pathway down-regulator. We suggest that under physiological conditions, factor H may serve as a downregulator of bacterially-driven inflammatory responses, thereby fine-tuning and balancing the inflammatory response in infections with Gram-negative bacteria.
Binding, Competitive ; immunology ; Complement Activation ; immunology ; Complement C1q ; chemistry ; immunology ; metabolism ; Complement C4b ; analysis ; Complement Factor H ; chemistry ; immunology ; metabolism ; Complement Pathway, Classical ; immunology ; Escherichia coli ; immunology ; metabolism ; Humans ; Iodine Radioisotopes ; Isotope Labeling ; Lipid A ; immunology ; metabolism ; Liposomes ; immunology ; metabolism ; Protein Binding ; immunology ; Recombinant Proteins ; chemistry ; immunology ; metabolism ; Substrate Specificity

OBJECTIVETo assess complement-mediated myocardial injury on isolated guinea pig working hearts and cardioprotective effects of CD59.

METHODSUsing a modified Langendorff apparatus, isolated guinea-pig working hearts were perfused with a modified Krebs Henseleit buffer containing 3% heat-inactivated human plasma and zymosan (IPZ) (control) (n = 10), 3% normal human plasma and zymosan (NPZ) (n = 10), or 3% normal human plasma and zymosan and 1.5 microg/ml CD59 (NPZC) (n = 10), respectively. Epicardial electrocardiogram (ECG), cardiac output (CO), coronary arterial flow (CF), maximum left ventricular developed pressure (LVP(max)), maximum left ventricular developed pressure increase rate (+ dp/dt(max)), maximum left ventricular developed pressure decrease rate (- dp/dt(max)) and heart rate (HR) were recorded at 0, 15, 30, 45 and 60 min of treatment. After the experiment, immunohistochemical examination was performed to detect the presence of C3a or C5b-9 in the myocardium of the isolated hearts.

RESULTSCompared the IPZ group, hearts treated with NPZ showed a slight depression on ST segments of epicardial ECG at 15 min, a significant elevation between 30 min to 60 min, a decrease in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max), and an increase in HR at 15 min. The observed alterations in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max) remained decreased, while the HR remained increased until the end of the protocol. The all above parameters of hearts treated with NPZC were similar to the control group (IPZ) at any given time. Immunohistochemical examination showed positive signals of C3a and C5b-9 in the myocardium of hearts treated with NPZ. C3a was positive in NPZC, and C3a and C5b-9 were negative in IPZ.

CONCLUSIONSActivated human complements directly damage isolated guinea pig working hearts, and CD59 offers a significant protection against the injuries.

Animals ; CD59 Antigens ; pharmacology ; Complement C3a ; antagonists & inhibitors ; metabolism ; Complement Inactivator Proteins ; pharmacology ; Electrocardiography ; Guinea Pigs ; Heart ; drug effects ; physiology ; Immunohistochemistry ; In Vitro Techniques ; Male ; Myocardium ; metabolism ; pathology ; Time Factors

BACKGROUND: Endogenous complement inhibitors in the brain may protect against the neuroinflammation in Alzheimer's disease. Human neuroblastoma cells were stimulated by Abeta1 - 4 2 to investigate whether the expression of various complement regulator genes is upregulated. METHODS: SK-N-SH cells were incubated overnight with a single dose of 20 microM of Abeta1-42 or 0.5 ng/ml - 5 ng/ml of TNFalpha or both. Actinomycin D (2.5 microM) or cycloheximide (2.5 microM) was also added to the cell suspension. Messenger RNA expression of decay accelerating factor (DAF), membrane cofactor protein (MCP), CD59, complement-receptor 1(CR1), C1 inhibitor (C1-INH), C4-binding protein, factor H, factor I, clusterin and S-protein was measured by RT-PCR. RESULTS: Abeta1-42 and TNFalpha upregulated the expression of C1- INH significantly but increased expression of mRNA for factor H was not statistically significant. The expression of mRNAs for DAF and MCP was at low a level after stimulation. Factor I, CD59 and clusterin were not changed in their mRNA level. The mRNAs for S-protein, C4-binding protein and CR1 were not detected. Actinomycin D suppressed mRNA levels of C1-INH and CD59 significantly. Cycloheximide also inhibited the expression of both C1-INH and CD59. CONCLUSIONS: Early upregulated expression of C1-INH in Abeta1-42 stimulated neuroblastoma cell may contribute to a host defense mechanism against complement-mediated neuronal cell damage.
Alzheimer Disease ; Amyloid beta-Peptides ; Antigens, CD46 ; Antigens, CD55 ; Antigens, CD59 ; Brain ; Clusterin ; Complement Factor H ; Complement System Proteins* ; Cycloheximide ; Dactinomycin ; Fibrinogen ; Genes, Regulator* ; Humans* ; Neuroblastoma* ; Neurons ; RNA, Messenger ; Tumor Necrosis Factor-alpha

BACKGROUND: Endogenous complement inhibitors in the brain may protect against the neuroinflammation in Alzheimer's disease. Human neuroblastoma cells were stimulated by Abeta1 - 4 2 to investigate whether the expression of various complement regulator genes is upregulated. METHODS: SK-N-SH cells were incubated overnight with a single dose of 20 microM of Abeta1-42 or 0.5 ng/ml - 5 ng/ml of TNFalpha or both. Actinomycin D (2.5 microM) or cycloheximide (2.5 microM) was also added to the cell suspension. Messenger RNA expression of decay accelerating factor (DAF), membrane cofactor protein (MCP), CD59, complement-receptor 1(CR1), C1 inhibitor (C1-INH), C4-binding protein, factor H, factor I, clusterin and S-protein was measured by RT-PCR. RESULTS: Abeta1-42 and TNFalpha upregulated the expression of C1- INH significantly but increased expression of mRNA for factor H was not statistically significant. The expression of mRNAs for DAF and MCP was at low a level after stimulation. Factor I, CD59 and clusterin were not changed in their mRNA level. The mRNAs for S-protein, C4-binding protein and CR1 were not detected. Actinomycin D suppressed mRNA levels of C1-INH and CD59 significantly. Cycloheximide also inhibited the expression of both C1-INH and CD59. CONCLUSIONS: Early upregulated expression of C1-INH in Abeta1-42 stimulated neuroblastoma cell may contribute to a host defense mechanism against complement-mediated neuronal cell damage.
Alzheimer Disease ; Amyloid beta-Peptides ; Antigens, CD46 ; Antigens, CD55 ; Antigens, CD59 ; Brain ; Clusterin ; Complement Factor H ; Complement System Proteins* ; Cycloheximide ; Dactinomycin ; Fibrinogen ; Genes, Regulator* ; Humans* ; Neuroblastoma* ; Neurons ; RNA, Messenger ; Tumor Necrosis Factor-alpha

No abstract available.
Complement Factor H*