Contole do angiodema hereditário com o estanazol / Control of herditary angiodema with stanzol

O angioedema herditário, forma congênita, é uma doença rara autossômica dominante, caracterizada por apresentar episódios de angiodema, localizados ou generalizados, potencialmente fatais, decorrentes da deficiência quantitativa e/ou qualitativa do inibidor de C1-esterase, induzindo a reduçäo ou ausência das fraçöes do complemento sérico C2, C4 e CH50. Apresentamos e discutimos os casos de dois irmäos portadores desta afecçäo, controlados adequadamente (quadros clínicos e imunoquímico) com o androgêno estanazol

Binding of complement components C1q, C3, C4 and C5 to a model immune complex in ELISA.

When normal human serum is added to microELISA plates coated with monomeric or aggregated IgG various complement components become bound and can be detected with specific chicken anti-C1q, anti-C3, anti-C4 and anti-C5 antibodies. Using such assays we found increased C1q- and decreased C3- and C4-binding in sera from patients with SLE. In contrast, sera from patients with rheumatoid arthritis showed decreased C3 binding but normal C1q binding. The decreases in C3 and C4 binding observed in the sera from patients with SLE were larger than the corresponding decreases determined by radial immunodiffusion. Comparing these results with those of the CH50 assay, the correlation coefficient between CH50 and the C3-binding assay was 0.48. There was no correlation between the results of the CH50 and those of the C1q-, C4- or C5-binding assays.

Hypocomplementemia and human immunodeficiency virus infection. Clinical correlates and relationships to circulating immune complex and immunoglobulin G levels.

The levels of C4 and C3 were measured and related to other immunological and clinical parameters in 44 patients with the human immunodeficiency virus (HIV) infection. Circulating immune complexes (C1q-CIC) as measured by an enzyme-linked immunosorbent assay employing monoclonal antibody with specificity for bound Clq, and serum immunoglobulin G (IgG) concentrations were assessed simultaneously. Clinical parameters assessed included: (1) the presence of specific anti-infective medications; (2) the presence of hypotension and fluid administration, and (3) bacterial and specific opportunistic infections. Hypocomplementemia was observed in 25 of 46 sera for C3, and in 8 of 46 sera for C4. Clq-CIC increases were seen in 26 of 46 sera and hyper-IgG was present in 25 of 46 sera. Lower C3 concentrations were significantly associated with elevated Clq-CIC levels (p less than 0.001). There were significant correlations between Clq-CIC levels and C3 concentrations (p = 0.0065, negative) and IgG levels (p = 0.0075, positive). Clq-CIC were significantly higher with serum p-24 antigen levels of 50 pg/ml or greater. These data demonstrate that elevated Clq-CIC and hypocomplementemia are both common in HIV-infected patients and may have significant relationships.

Plasma anaphylatoxin concentrations in inflammatory skin diseases.

To study the possible involvement of the complement system in inflammatory skin disorders, we measured the concentrations of C3a and C4a anaphylatoxins in the peripheral blood of 148 patients with various inflammatory skin disorders and 48 healthy control subjects by radioimmunoassay. Significant increases in mean levels of both C3a and C4a anaphylatoxins were found in 59 patients with psoriasis. Remarkable increases in both C3a and C4a anaphylatoxins were also noted in some patients with leukocytoclastic vasculitis, urticarial vasculitis or unspecified toxic erythema. On the other hand, elevation of C4a alone was noted in a case of systemic lupus erythematosus. In contrast, using the mean of the normal control +/- 2 S.D., no significant anaphylatoxin elevation was found in 16 patients with pustulosis palmaris et plantaris, 7 with pityriasis rosea, 3 with erythema multiforme, and 3 with erythema nodosum or autoimmune bullous dermatoses.

Complement activation in primary biliary cirrhosis: an in vitro model.

Increased concentrations of C3dg were demonstrated in plasma from patients with primary biliary cirrhosis (PBC), indicating in vivo activation of C3. Rapid spontaneous C3 cleavage by the classical pathway was observed in vitro in serum and in EDTA plasma reconstituted with Ca++ and Mg++, suggesting the presence of complement-activating substances. On incubation with fresh normal serum, purified polyclonal IgM from patients with PBC induced C1 activation, C4 cleavage, and C3dg formation. No C3 cleavage was observed when PBC-IgM was incubated with a C2-deficient serum. We suggest that the complement activation in vivo in PBC, which occurs predominantly by the classical pathway and is characterized by increased concentrations of C1 activation complexes, decreased C4 concentrations, and hypercatabolism of C3, is attributable to an abnormal IgM population.

Complement activation after myocardial infarction.

Complement activation as reflected by C3, C4, and C3d levels was studied in 56 patients following myocardial infarction, 13 with the postmyocardial infarction syndrome (PMIS); 12 with prolonged postinfarction pyrexia; six with clinical evidence of pulmonary embolism; and 25 control patients without apparent complications. In most patients, C3d levels were elevated during the first ten postinfarction days and at the time of any pulmonary embolism; this probably represented local nonimmunologic complement utilization. The PMIS patients had much higher C3d levels associated with significantly lower concentrations of C3 at the time of disease activity. It is suggested that heart reactive antibodies combine with circulating cardiac antigens to form soluble immune complexes, and in the PMIS, these may become deposited in various sites resulting in complement-mediated tissue damage. The high C3d levels associated with the PMIS may also be of value in differentiating this condition from pulmonary embolism, as both problems may have similar clinical and roentgenographic features.

Plasma lactoferrin reflects granulocyte activation via complement in burn patients.

Complement activation and neutropenia have been observed in thermally injured animals. In burn patients, granulocyte chemotaxis and morphological loss of specific granules occur. We conjectured that complement is activated in humans and, in turn, induces granulocytes to secrete lactoferrin (LF), a marker of granulocyte activation. Twenty burn patients were evaluated for absolute granulocyte count (AGC), plasma levels of anaphylatoxins (C3a, C4a, C5a), and lactoferrin. The AGC directly correlated with the extent of the burn on day 1. Similarly, plasma LF on day 1 correlated with the percent burn. Those with greater than 30% burn had plasma LF between 10 and 40 micrograms/ml (normal LF = 1.5 +/- 1.8 micrograms/ml). In five patients without further complications followed serially, plasma LF did not return to normal until 2 to 5 weeks. In all patients, there was evidence of complement activation; C4a ranged between 283 and 13,064 ng/ml and C3a between 19 and 852 ng/ml. In some patients, C5a was detectable, but the values correlated inversely with the extent of burn. On the other hand C3a and C4a levels did not correlate with the extent of burn but threefold to fivefold rises of C3a levels on days 7 and 9 predicted gram-negative sepsis. Although plasma LF did not predict sepsis, levels greater than 12 micrograms/ml on day 1 heralded the onset of neutropenia on day 3 in 60% of patients with 30% burn. Six of 20 patients developed pulmonary radiographic changes and, in five of the six, the changes occurred by day 3. Plasma LF in all six patients on day 1 was greater than 17 micrograms/ml. In two patients with greater than 50% burn, depletion of granulocyte LF was demonstrated histochemically. These studies indicate that complement is activated in burn patients, which is associated with granulocyte secretion. Measurement of plasma anaphylatoxins and LF may serve as useful aides in clinical management of these patients.

Rapid turbidimetric determination of serum C3c and C4 by end point centrifugal analysis.

An end point turbidimetric method for the determination of C3c and C4 in serum using a centrifugal analyzer (Cobas Bio) is described. Several analytical factors were evaluated -pH, temperature, PEG and antibody concentration. Wide variations of temperature and pH did not significantly affect the turbidimetric reaction. A 20 g/L PEG concentration and 25-fold antiserum dilution were found satisfactory for the analysis. Precision of the assay was good and comparison with a RID method yielded an r value of 0.97. The procedure is simple and reliable.

The clinical significance of the antinuclear antibody test as a screening procedure for DNA antibodies in SLE.

During the two-year period (1st October 1974-30th September 1976), 2979 sera were tested for DNA antibodies by the Farr test. One thousand six hundred and ninety-five of these were tested because they had high ANA titres (1/256 or greater). In this group 285 sera were found to have raised DNA binding capacities (DNA-bc), 86 of which were found in patients having diagnoses other than SLE. When the diagnoses were reviewed following the finding of a raised DNA-bc, 55 of these patients were found to be suffering from SLE. Of the 1284 sera tested for DNA antibodies without the prior ANA screening procedures, 288 were positive, 36 of which came from patients not considered to have SLE; 30 of these patients were subsequently shown to have SLE. Thus the DNA-bc test is an important tool in the diagnosis of SLE, and the ANA test appears to be a valuable screening procedure. The level of DNA-bc was not of any diagnostic value.

Hereditary angioneurotic edema and Charcot-Marie-Tooth disease in the same family.

In one family two genetic diseases were transmitted as autosomal dominant traits; hereditary angioneurotic edema was inherited from the paternal side and Charcot-Marie Tooth disease from the maternal side of the family. The conditions occurred separately in 8 and 11 members respectively and together (an exceedingly rare occurrence) in 3. Of six siblings, two girls and four boys, all had Charcot-Marie-Tooth disease, and three, the two girls and one of the boys, also had hereditary angioneurotic edema.