Medical Literature - 1993

Autoimmune C1 inhibitor deficiency: report of eight patients

Cicardi M, Bisiani G, Cugno M, Spath P, Agostoni A 8/1993 The American Journal of Medicine

PURPOSE: In this study, we investigated the clinical and biochemical features and the responses to treatment of eight patients with auto-antibody-mediated C1 inhibitor (C1-INH) deficiency and symptoms of angioedema.

PATIENTS AND METHODS: In addition to the 8 patients with acquired angioedema (AAE), we also studied 36 subjects with hereditary angioedema (HAE), 15 of them treated with C1-INH plasma concentrate, and 26 patients with different autoantibodies in their plasma (10 with systemic lupus erythematosus, 6 with lupus-like anticoagulant, and 10 with chronic liver disease). Functional C1-INH was measured with the reagent kit of Immuno (Vienna, Austria); C1-INH, C4, and C1q antigen were determined by radial immunodiffusion; and autoantibodies to C1-INH were detected by an enzyme-linked immunosorbent assay method.

RESULTS: Four patients with AAE had no other diseases, one had breast cancer, one liver hydatidosis, one Waldenstrom’s disease, and one a benign M component. Functional C1-INH levels were below 30% of normal, and C1q plasma levels were low in seven patients but normal in one. Autoantibodies to C1-INH were detectable in all eight AAE patients but in none of the others. Prophylactic treatment with attenuated androgens was successful in one of four patients, and with antifibrinolytic agents (tranexamic acid) in six of seven patients. Laryngeal attacks in five patients were treated with C1-INH plasma concentrate; two patients had marked clinical and biochemical responses. In three, the symptoms resolved only with high doses, and the biochemical parameters did not significantly increase.

CONCLUSIONS: Our results suggest that patients with autoimmune AAE are clinically and biochemically heterogeneous. They have different responses to treatment that seem to be related to variable C1-INH consumption.


Available at: (small fee)

Clinical problems in the C1-inhibitor deficient patient

Agostoni A, Cicardi M, Cugno M, Storti E /1993 Behring Institute Mitteilungen

The clinical course of C1-INH deficiency is presently well established. There is an inherited form (Hereditary Angioedema) characterized by recurrence of cutaneous and mucous swellings appearing early in life and usually accompanied by substantial family history, and an acquired form (Acquired Angioedema) where identical symptoms start after the fourth decade of life without family history. The acquired form can be associated with other diseases, mainly B cell disorders, and/or with autoantibodies to C1-INH. The biochemical characteristic is the functional deficiency of C1-INH and of C4 and C2. Moreover a marked deficiency of C1 is present in most acquired forms, but never in the inherited ones. C1-INH deficiency can be corrected by attenuated androgens that increase C1-INH levels in a few days and are effective in the prophylaxis of attacks, or by substitutive therapy with C1-INH plasma concentrate that is the life-saving drug in laryngeal edema. Patients with the inherited form have a uniformly good response to both these treatments which are otherwise effective only in a minority of patients with the acquired deficiency. In these subjects C1-INH concentrate needs to be given in higher doses and prevention of attacks is obtained with antifibrinolytic agents (Tranexamic acid).

Not available online.

Influence of C1-inhibitor on inflammation, edema and shock

Dickneite G /1993 Behring Institute Mitteilungen

C1-Inhibitor (Berinert, C1 INH), a 104 kDa protein, inhibits complement components (C1 esterase) as well as enzymes of the contact phase of coagulation (Factor XII, Factor XI) and kallikrein, thus regulating kinin generation. C1 INH is used for the treatment of the hereditary angioneurotic edema. This paper will give a survey about the evidence in recent literature concerning the potential efficacy of the compound on other diseases associated with shock, capillary leakage and inflammation as well. In our own experiments we evaluated whether the compound could influence acute inflammatory reactions or the severe systemic inflammatory response syndrome (SIRS) as a consequence of an experimental septic shock. To prevent the sepsis-induced DIC we co-infused the thrombin inhibitors AT III or rec. hirudin in combination with C1 INH. Coinfusion of C1-inhibitor (50-200 U/kg x h) with either rec. hirudin or AT III significantly improved survival rate compared to thrombin inhibitor alone. [References: 48].

Mutations in the C1 inhibitor gene that result in hereditary angioneurotic edema

Davis AE 3rd, Bissler JJ, Cicardi M /1993 Behring Institute Mitteilungen

Mutations in one C1 INH allele result in the autosomal dominant disease, hereditary angioedema. The plasma antigenic level of C1 INH in this disease may be low, normal, or high, while the functional level is uniformly depressed. Investigation of the mutations in the C1 INH gene reveal several key features about the DNA itself as well as protein structure-function relationships. The largest single group of mutations with a defined mechanism are recombinations associated with Alu repetitive DNA elements. Current data suggest that there may be an increased number of mutations within the region encoding the reactive center which, like some other serpins, contains both primary and secondary structure DNA polymerase pause sites. These sites may enhance the rates of mutation and evolution in the reactive center region. Some of the dysfunctional C1 INH proteins that result from hinge region mutations support models for reactive center loop interaction with beta sheet A during complex formation. The analysis of the dysfunctional mutants, therefore, suggest regions of the molecule that are important for inhibitor function. [References: 45].

Not available online.

Funding for Canadian Hereditary Angioedema Network has been generously provided by unrestricted grants from:


CSL Behring


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