Acquired Cold Urticaria vs. Autoinflammatory Diseases, Genetic and Clinical Profile and Differential Diagnosis: Study of a Cohort of Patients in a Tertiary Reference Centre
Open accessAbstract
Acquired cold urticaria (ACU) is characterized by the development of itchy wheals after cold exposure. Generalized urticarial skin rashes triggered by cold exposure characterize certain monogenic autoinflammatory diseases (AIDs). The objective of this study is to investigate the presence of variants in genes causing AIDs that present with cold-induced urticarial skin rashes in patients clinically diagnosed with ACU, in order to look for susceptibility factors for the disease. Fifty patients with primary ACU were studied. Germline and post-zygotic variants on the NLRP3, NLRP12, NLRC4 and PLCG2 genes were investigated using next-generation sequencing technology. Seven patients (14%) carried 8 heterozygous germline variants in the following genes: NLRP3 (n = 1), NLRP12 (n = 3), NLRC4 (n = 1), PLCG2 (n = 3). No pathogenic or likely pathogenic variants were detected, and deep analyses of the sequences obtained did not identify any post-zygotic variant. In conclusion, ACU is not related to post-zygotic or germline pathogenic variants in the NLRP3, NLRP12, NLRC4 and PLCG2 genes.
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A significant gain of function of PLCγ2 can lead to deleterious impacts on the immune system.
“These clearly indicate that a significant gain of function of PLCγ2 can lead to deleterious impacts on the immune system.”
From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [34]
The Discussion (page unavailable) describes immune harms associated with PLAID, including recurrent infections, hypogammaglobulinaemia and autoimmunity. However, the paper does not identify significant gain of function of PLCγ2 as their cause; its Results found no pathogenic or likely pathogenic PLCG2 variants in the studied cohort. (LLM, conf=0.82)
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- Authors
- Deza, G., Mensa-Vilaró, A., March-Rodriguez, A., Sánchez, S., Pujol, R., Aróstegui, J., & Giménez-Arnau, A.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Hospital Clínic de Barcelona (ES)
- Venue
- Acta Dermato Venereologica
- Published
- 2019
- Volume
- 99
- Issue
- 12
- Pages
- 0
- ISSN
- 0001-5555 (ISSN-L)
- OpenAlex
- W2977612900
- Cited by
- 17
- References
- 31
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Acta Dermato Venereologica (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Ministerio de Economía y Competitividad (SAF2015-68472-C2-1-R)
- Universitat Autònoma de Barcelona
- LEO Pharma
- Genentech
- Instituto de Salud Carlos III (AC15/00027, PI17/00198)
- European Regional Development Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Rheumatology › Urticaria and Related Conditions
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- autoinflammatory disease, NLRP3, NLRP12, NLRC4, PLCγ2, germline mutations, cold-induced urticaria, differential diagnosis, genetic susceptibility
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adolescent, Adult, Aged, Calcium-Binding Proteins, Child, Child, Preschool, Cold Temperature, Female, Humans, Infant, Male, Middle Aged, Phenotype, Prospective Studies, Risk Factors, Spain, Urticaria, Genetic Variation, Genetic Predisposition to Disease, Intracellular Signaling Peptides and Proteins, Phospholipase C gamma, CARD Signaling Adaptor Proteins, Young Adult, Hereditary Autoinflammatory Diseases, Tertiary Care Centers
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