C3, prekallikrein, total kininogen, high molecular weight kininogen (HK), alpha-2-macroglobulin and factor XII were not significantly different in HAE patients.
As an approach to effectively treat HAE with a single treatment, we hypothesized that a one-time intravenous administration of an adeno-associated virus (AAV) gene transfer vector expressing the genetic sequence of the normal human C1 esterase inhibitor (AAVrh.10hC1EI) would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes.
Other genetic markers studied were generally noninformative, although evidence was obtained against close linkage of the loci for HAE and ABO and HAE and transferrins.
To describe unique features of HAE in Spanish carriers of the F12 mutation and investigate a potential role for angiotensin-converting enzyme (ACE) and aminopeptidase-P polymorphisms in disease expression.
A literature review was conducted concerning the clinical characteristics and pathophysiology of types I and II hereditary angioedema (HAE), type III HAE, acquired C1 inhibitor (C1INH) deficiency, and angiotensin-converting enzyme (ACE) inhibitor-associated angioedema.
The FXII-HAE is associated with modifiers, for example kinin catabolism enzymes, ACE and CPN, different from those recognized in HAE with C1Inh deficiency.
Upregulation of 2 genes, those encoding adrenomedullin and cellular receptor for urokinase plasminogen activator (uPAR), which occurs during an acute attack, was confirmed in PBMCs of 20 additional patients with HAE by using real-time PCR.
Compared to healthy controls patients with C1-INH-HAE in the symptom-free period had significantly decreased serum fetuin-A 258 μg/ml (224-285) vs. 293 μg/ml (263-329), (median (25-75% percentiles, p = 0.035) and TNFα 2.53 ng/ml (1.70-2.83) vs. 3.47 ng/ml (2.92-4.18, p = 0.0008) concentrations.
C1 inhibitor concentrate or albumin (placebo) infusions were administered in a blind fashion to HAE patients who came to the hospital for treatment no later than 5 hours after an attack began.
The ANGPT1p.A119S variant was detected in all members of the index family with U-HAE but not in asymptomatic family members or an additional 20 patients with familial U-HAE, 22 patients with sporadic U-HAE, and 200 control subjects.
The recent discovery of associations between PLG K330E and ANGPT1A119S and HAE of unknown genetic cause (HAE-U), has raised the possibility that genetic evaluation could be used to diagnose HAE-U in patients with unexplained angioedema or non-confirmatory laboratory testing.
This abnormality is thought to be responsible for the generation of a kininlike peptide in HAE plasma that is derived from the second component of complement (C2).
However, the addition to HAE plasma of C2 at 20 X normal plasma concentration had no effect on the kinin activity generated on incubation at 37 degrees.
These observations indicate that high copy number of the C4B gene can be a protective factor against disease severity in HAE and therefore its determination is warranted.
Together, these data suggest that RNAi-mediated knockdown of FXII by ALN-F12 is a potentially promising approach for the prophylactic treatment of HAE.
To describe unique features of HAE in Spanish carriers of the F12 mutation and investigate a potential role for angiotensin-converting enzyme (ACE) and aminopeptidase-P polymorphisms in disease expression.
In this study we aimed to determine serum fetuin-A, C-reactive protein (CRP) and tumor necrosis factor alpha (TNFα) concentrations in patients with C1-INH-HAE during symptom-free period and during attacks and compare them to those of healthy controls.