Baseline level of functional C1-inhibitor correlates with disease severity scores in hereditary angioedema

Background: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. Methods: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. Results: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0–18.7; 5.8%, 0–16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11–78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = –0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = –0.404, p = 0.001) and more frequent annual attacks (r = –0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. Conclusion: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.

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“…1) [13]. C1 inhibitor function has also been reported to be positively correlated with another disease severity index [24]. …”

Section: Discussionmentioning

confidence: 99%

“…Serum C1q values are expected to remain normal in C1-INH-HAE and are known to be depressed in the acquired form of angioedema [24]. However, some exceptions do exist.…”

Section: Discussionmentioning

confidence: 99%

Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Gökmen

Gülbahar

Önay

et al. 2018

Int Arch Allergy Immunol

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“…Complement C4 and the functional C1-INH (C1-INHf) levels were measured according to Kelemen et al [16] Antigenic C1-INH (C1-INHa) levels were measured by in-house-ELISA, using goat-anti-human-C1-INH antibodies [6].…”

Section: Measurement Of Laboratory Parametersmentioning

confidence: 99%

Novel Vasoregulatory Aspects of Hereditary Angioedema: the Role of Arginine Vasopressin, Adrenomedullin and Endothelin-1

et al. 2016

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The elevation of bradykinin (BK) level during attacks of hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) is well known. We previously demonstrated that endothelin-1 (ET-1) level also increases during C1-INH-HAE attacks. Although BK and ET-1 are both potent vasoactive peptides, the vasoregulatory aspect of the pathomechanism of C1-INH-HAE has not yet been investigated. Hence we studied the levels of vasoactive peptides in controls and in C1-INH-HAE patients, as well as evaluated their changes during C1-INH-HAE attacks. The levels of arginine vasopressin (AVP), adrenomedullin (ADM) and ET-1 were measured in the plasma of 100 C1-INH-HAE patients in inter-attack periods and of 111 control subjects, using BRAHMS Kryptor technologies. In 18 of the 100 C1-INH-HAE patients, the levels of vasoactive peptides were compared in blood samples obtained during attacks, or in inter-attack periods. AVP, ADM and ET-1 levels were similar in inter-attack samples from C1-INH-HAE patients and in the samples of controls, although cardiovascular risk has an effect on the levels of vasoactive peptides in both groups. The levels of all three vasoactive peptides increased during C1-INH-HAE attacks. Moreover, the levels of ET-1 and ADM as well as their changes during attacks were significantly correlated. This study demonstrated that vascular regulation by vasoactive peptides is affected during C1-INH-HAE attacks. Our results suggest that the cooperation of several vasoactive peptides may be necessary to counterbalance the actions of excess BK, and to terminate the attacks. This may reveal a novel pathophysiological aspect of C1-INH-HAE.

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“…2 A recent study, however, found a significant correlation between severity scores and baseline functional C1-esterase inhibitor levels, which suggests the potential significance of monitoring functional C1-esterase levels in relation to clinical disease course. 38 …”

Section: Diagnosismentioning

confidence: 99%

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

Gower

Busse

Aygören‐Pürsün

et al. 2011

World Allergy Organization Journal

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Abstract:Hereditary angioedema (HAE) caused by C1-esterase inhibitor deficiency is an autosomal-dominant disease resulting from a mutation in the C1-inhibitor gene. HAE is characterized by recurrent attacks of intense, massive, localized subcutaneous edema involving the extremities, genitalia, face, or trunk, or submucosal edema of upper airway or bowels. These symptoms may be disabling, have a dramatic impact on quality of life, and can be life-threatening when affecting the upper airways. Because the manifestations and severity of HAE are highly variable and unpredictable, patients need individualized care to reduce the burden of HAE on daily life. Although effective therapy for the treatment of HAE attacks has been available in many countries for more than 30 years, until recently, there were no agents approved in the United States to treat HAE acutely. Therefore, prophylactic therapy is an integral part of HAE treatment in the United States and for selected patients worldwide. Routine long-term prophylaxis with either attenuated androgens or C1-esterase inhibitor has been shown to reduce the frequency and severity of HAE attacks. Therapy with attenuated androgens, a mainstay of treatment in the past, has been marked by concern about potential adverse effects. C1-esterase inhibitor works directly on the complement and contact plasma cascades to reduce bradykinin release, which is the primary pathologic mechanism in HAE. Different approaches to long-term prophylactic therapy can be used to successfully manage HAE when tailored to meet the needs of the individual patient.

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Baseline level of functional C1-inhibitor correlates with disease severity scores in hereditary angioedema

Cited by 43 publications

References 19 publications

Deletions in <b><i>SERPING1</i></b> Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Deletions in <b><i>SERPING1</i></b> Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Novel Vasoregulatory Aspects of Hereditary Angioedema: the Role of Arginine Vasopressin, Adrenomedullin and Endothelin-1

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

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