Successful allogeneic cord blood transplantation in a patient with Evans syndrome leads to correction of hereditary angioedema type I as secondary effect

Klausegger, Alfred; Wiednig, Michaela; Urban, Christian; Lackner, Herwig; Reiter, Harald; Bauer, Jan; Aberer, Werner

doi:10.1038/bmt.2012.7

Cited by 6 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The amount of C1 INH produced by the transplanted macrophages is likely to be minor compared with that produced in the liver. This observation supports the notion that even a small increase in wild-type C1 INH by any method may alter the phenotype of the patient (46). …”

Section: In Vivo Gene Editing Including the Crispr Cas9 Systemsupporting

confidence: 86%

Hereditary Angioedema as a Metabolic Liver Disorder: Novel Therapeutic Options and Prospects for Cure

et al. 2016

View full text Add to dashboard Cite

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by mutations of the SERPING1 or the Factor 12 genes. It is potentially fatal, particularly if not identified at an early stage. Apart from androgens, which are contraindicated in children and in pregnant women, a range of effective, albeit very expensive treatments have recently become available for HAE patients. The cost of these new treatments is beyond the reach of most developing countries. At this time, there is no cure for the disorder. In spite of mutations of the SERPING1 gene, autoimmunity and infections are not prominent features of the condition. Here, we present the argument that HAE should be viewed primarily as a metabolic liver disorder. This conceptual paradigm shift will stimulate basic research and may facilitate new therapeutic approaches to HAE outlined in this paper. We suggest several novel potential treatment options for HAE from the perspectives of clinical immunology, molecular biology, and liver transplantation. Many of these offer the prospect of curing the disorder. The effectiveness of these options is rapidly improving in many cases, and their risks are decreasing. Given the very high costs of treating HAE, some of these curative options may become feasible in the next decade.

show abstract

Section: In Vivo Gene Editing Including the Crispr Cas9 Systemsupporting

confidence: 86%

Hereditary Angioedema as a Metabolic Liver Disorder: Novel Therapeutic Options and Prospects for Cure

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This interpretation of the results differs from reports by Klausegger et al describing a child affected of Evans syndrome and HAE, whose angioedema symptoms were clinically and biochemically cured by stem cell bone marrow transplantation [20]. Although the authors report a complete cure of HAE signs which is supported by the rising in serum C1-Inh function from 5-50% to 84% of control values, circulating levels of C4 in the patient are still at the lower limit of normality two years after transplantation (11.2 mg/dL).…”

Section: Discussioncontrasting

confidence: 99%

Disease-modifying factors in hereditary angioedema: an RNA expression-based screening

López-Lera

Sánchez‐Cabo

Garrido

et al. 2013

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundHereditary Angioedema due to C1-Inhibitor deficiency (HAE types I and II) is a monogenic disease characterized by sudden, self-limited episodes of cutaneous and mucosal swelling due to local deregulation of vascular permeability. Despite its monogenic pattern of inheritance, HAE exhibits great clinical variability and low genotype/phenotype correlation among those affected, which ultimately hinders therapeutic approach and probably underlies yet unknown genetic and environmental factors.MethodsWe studied whole-genome RNA expression of PBMCs in three HAE type-I families (accounting for 40 individuals), 24 of which carry the same R472X mutation in the C1-Inhibitor gene and show large variability in terms of disease expression. Those included in this study were analyzed according to the presence of mutation and/or clinical symptoms.ResultsInstead of a single, common disease-associated expression pattern, we found different transcriptome signatures in two of the families studied. In one of them (referred to as DR family), symptoms correlate with the upregulation of 35 genes associated to the biological response to viral infections (including RSADs, OAS, MX and ISG pathway members) and immune response. In another pedigree (Q family), disease manifestation is linked to the upregulation of 43 genes with diverse functions, including transcription and protein folding. Moreover, symptoms-free members of the Q pedigree display relatively higher expression of 394 genes with a wide diversity of functions.ConclusionWe found no evidence for a common altered PBMC expression pattern linked to HAE symptoms in the three families analyzed. All the data considered, differential gene expression in PBMCs do not seem to play a significant role in the predisposition or protection against HAE in the basal -between crises- conditions analyzed. Although the RNA expression pattern associated to the response to viral infections observed in the DR family supports the idea of infectious diseases as a modifying factor for HAE severity, large-scale studies would be needed to statistically associate such expression pattern to the development of this rare disease.

show abstract

“…However, several cases have been reported in which HSCT has resulted in restoration of functional C1q and resolution of SLE symptoms [151,152]. There have also been some reports of favorable responses to HSCT in HAE where hematopoietic production of C1-INH appeared sufficient to prevent attacks [153,154] and for alloSCT in acquired angioedema [155]. As an alternative to HSCT, combined liver and kidney transplantation has the potential to correct aHUS if the proteins encoded by the deficient genes are predominantly synthesized in the liver, such as FH or FI [156].…”

Section: Hematopoietic Stem Cell Transplantation (Hsct)mentioning

confidence: 99%

European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management

Brodszki

Frazer‐Abel

Grumach³

et al. 2020

J Clin Immunol

View full text Add to dashboard Cite

This guideline aims to describe the complement system and the functions of the constituent pathways, with particular focus on primary immunodeficiencies (PIDs) and their diagnosis and management. The complement system is a crucial part of the innate immune system, with multiple membrane-bound and soluble components. There are three distinct enzymatic cascade pathways within the complement system, the classical, alternative and lectin pathways, which converge with the cleavage of central C3. Complement deficiencies account for ~5% of PIDs. The clinical consequences of inherited defects in the complement system are protean and include increased susceptibility to infection, autoimmune diseases (e.g., systemic lupus erythematosus), age-related macular degeneration, renal disorders (e.g., atypical hemolytic uremic syndrome) and angioedema. Modern complement analysis allows an in-depth insight into the functional and molecular basis of nearly all complement deficiencies. However, therapeutic options remain relatively limited for the majority of complement deficiencies with the exception of hereditary angioedema and inhibition of an overactivated complement system in regulation defects. Current management strategies for complement disorders associated with infection include education, family testing, vaccinations, antibiotics and emergency planning.

show abstract

Successful allogeneic cord blood transplantation in a patient with Evans syndrome leads to correction of hereditary angioedema type I as secondary effect

Cited by 6 publications

References 8 publications

Hereditary Angioedema as a Metabolic Liver Disorder: Novel Therapeutic Options and Prospects for Cure

Hereditary Angioedema as a Metabolic Liver Disorder: Novel Therapeutic Options and Prospects for Cure

Disease-modifying factors in hereditary angioedema: an RNA expression-based screening

European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management

Contact Info

Product

Resources

About