Background: Giant cell arteritis (GCA) is the most common vasculitis in people over 50 in Western countries [1]. Currently, we can identify two different phenotypes of the disease depending on the presence of predominant cranial or extracranial manifestations [1]. However. the mechanisms underlying these two phenotypes are poorly understood. In this context, inflammasomes are cytoplasmic protein complexes that play a crucial role in protecting the host against pathogenic and sterile stressors by initiating inflammation [2]. Thus, inflammasomes have been involved in several autoimmune diseases, being one of the most relevant the nucleotide oligomerization domain leucine-rich repeat pyrin-domain containing protein 1 (NLRP1) [3]. In particular, there is increasing attention being placed on genetic polymorphisms that are involved in the components of inflammasomes [3], therefore it is plausible to think that NLRP1 has a relevant role in GCA.

Objectives: To determine the potential role of NLRP1 in the pathogenesis of GCA and to evaluate whether this gene may be used as a biomarker for differential diagnosis between extracranial and cranial large vessel vasculitis phenotypes.

Methods: A total of 135 patients diagnosed with GCA, 105 with extracranial large-vessel GCA who had no cranial ischaemic manifestations of GCA, and 30 with biopsy-proven GCA who had typical cranial manifestations of the disease, were included in the present study. In addition, 192 ethnically matched unaffected controls were also recruited. Five single-nucleotide polymorphisms within the NLRP1 gene (rs4790797, rs8182352, rs878329, rs2670660, and rs12150220), previously associated with different immune-mediated diseases, were genotyped in all the patients with GCA and healthy controls using TaqMan probes.

Results: No statistically significant differences in the genotype and allele frequencies of the six NLRP1 polymorphisms evaluated were found when the whole cohort of GCA patients and healthy controls were compared (Table 1). It was also the case when extracranial and cranial phenotypes were compared between them or when each of these subgroups was related to healthy controls (Table 1). In addition, no statistically significant haplotype differences were discovered when we compared all the groups above-mentioned (data not shown).

Conclusion: Our results showed that NLRP1 polymorphisms do not influence the phenotypic expression of GCA.

REFERENCES: [1] Rheumatology (Oxford). 2017 Apr 1;56(4):506-515.

[2] MedComm. 2023 Oct 9;4(5):e391.

[3] J Autoimmun. 2015 Jul:61:1-8.

Funding: VP-C is supported by funds of NVAL23/02 from IDIVAL; RL-M is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF (“Investing in your future”) (CPII21/00004); MSM-G is supported by funds of “Fondo de Investigaciones Sanitarias” from ISCIII (PI121/00042) and JCB-L is a recipient of a PFIS program fellowship from the ISCIII, co-funded by the European Social Fund (‘Investing in your future’), (FI22/00020). The research has also been made possible thanks to the Aid for research projects without public funding for emerging researchers (Spanish Rheumatology Foundation 2023).

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Acknowledgements: We thank all the subjects that participated in this study.

Disclosure of Interests: Verónica Pulito-Cueto: None declared, Raquel López-Mejías: None declared, Javier Loricera: None declared, María Sebastián Mora-Gil: None declared, Joao Batista-Liz: None declared, Diana Prieto-Peña: None declared, Alejandro Muñoz Jimenez.: None declared, Francisco Ortiz-SanJuan: None declared, Susana Romero-Juste: None declared, Clara Moriano: None declared, Eva Galíndez-Agirregoikoa: None declared, Norberto Ortego-Centeno: None declared, Noelia Alvarez-Rivas: None declared, Santos Castañeda: None declared, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD., Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD., Abbvie, MSD, and Roche.