ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2505

C5 Signaling Pathway Genes as Key Drivers of the Pathogenesis of IgA Vasculitis?

Joao Carlos Batista-Liz1, Vanesa Calvo-Rio2, María Sebastián Mora-Gil3, Ligia Gabrie-Rodriguez4, Rafael Gálvez Sánchez4, Belén Sevilla-Pérez5, José Luis Callejas6, María Teresa Leonardo7, Ana Peñalba7, Javier Narvaez-García8, Luis Martín-Penagos9, Luis Caminal-Montero10, PAZ COLLADO11, Patricia Quiroga Colina12, Esther Vicente-rabaneda13, Esteban Rubio14, Manuel León Luque15, Juan María Blanco-Madrigal16, Eva Galindez-Agirregoikoa17, Santos Castañeda13, Ricardo Blanco-Alonso18, Veronica Pulito-Cueto1 and Raquel Lopez-mejias1, 1IDIVAL, Santander, Spain, 2Valdecilla Hospital, Santander, Cantabria, Spain, 3Immunopathology Group, IDIVAL, Santander, Spain, 4Immunopathology Group, IDIVAL. Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain, 5Division of Pediatrics, Hospital Universitario San Cecilio, Granada, Spain, 6Systemic Autoimmune Diseases Unit, Hospital Clinico San Cecilio, Instituto de Investigación Biosanitaria de Granada ibs.GRANADA, Granada, Spain, 7Division of Pediatrics, Hospital Universitario Marqués de Valdecilla, Santander, Spain, 8Hospital Universitario de Bellvitge, Barcelona, Spain, 9Immunopathology Group, IDIVAL. Division of Nephrology, Hospital Universitario Marqués de Valdecilla, Santander, Spain, 10Internal Medicine Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain, 11Hospital Universitario Severo Ochoa, MADRID, Spain, 12Division of Rheumatology, Hospital Universitario de La Princesa, Madrid, Spain, 13Hospital Universitario de La Princesa, Madrid, Spain, 14Division of Rheumatology, Hospital Universitario Virgen del Rocío, Sevilla, Spain, Sevilla, Spain, 15Division of Rheumatology, Hospital Universitario Virgen del Rocío, Sevilla, Spain., Sevilla, Spain, 16Division of Rheumatology, Hospital Universitario de Basurto, Bilbao, Spain., Bilbao, Spain, 17BASURTO UNIVERSITY HOSPITAL, BILBAO, Spain, 18Division of Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL, Immunopathology group, Santander, Spain

Meeting: ACR Convergence 2024

Keywords: , , , ,

Session Information

Date: Monday, November 18, 2024

Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Immunoglobulin A Vasculitis (IgAV) is an inflammatory disease caused by the accumulation of immune complexes of IgA in the walls of small blood vessels [1]. These immunocomplexes have been shown to activate the mannan-binding lectin and the alternative complement pathway [2]. Moreover, complement system components have been observed in skin and kidney biopsies in IgAV patients [3]. In this context, the complement protein C5a (a fragment cleaved from the C5 complement factor), together with its receptor, C5aR1, have been proposed as therapeutic targets in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [4], another small-vessel vasculitis [1]. Nevertheless, the molecular mechanisms by which the complement is involved in IgAV are poorly understood. In light of this, this work aimed to determine whether C5 and C5AR1 represent novel genetic risk factors for IgAV.

Methods: 346 patients with IgAV, the largest series of Caucasian patients with IgAV ever assessed for genetic studies, and 764 healthy ethnically matched controls (HC), were recruited for this study. Among the IgAV patients, 33.8% (117) presented nephritis (IgAV-N). Eight tag single nucleotide polymorphisms (SNPs) within C5 (rs16910280, rs3815467, rs10156396, rs10818495, rs7868761, rs4310279, rs74971050, and rs10760128) and 3 C5AR1 tag SNPs (rs10853784, rs11673071, and rs11670789) were genotyped by qPCR using TaqMan Probes. p-values < 0.05 after Benjamini-Hochberg correction for an FDR of 5% were considered statistically significant.

Results: No statistically significant difference was found in C5 and C5AR1 genotype and allele frequencies between patients with IgAV and HC (Table 1). Likewise, when IgAV patients were stratified according to the severity of the disease, represented by the presence or absence of renal manifestations, we did not observe differences of statistical significance in the genotype and allele frequencies of C5 and C5AR1. Moreover, when IgAV patients were stratified according to other clinical aspects, such as the age at disease onset or the presence/absence of articular and gastrointestinal manifestation, no significant differences were observed in the genotype and allele frequencies in C5 and C5AR1 (Table 1). Furthermore, no differences in the haplotype frequencies of C5 and C5AR1 were observed between IgAV patients and HC (Table 2), and between IgAV patients stratified according to the severity of the disease (Table 2) as well as to other clinical manifestations (Table 2).

Conclusion: Our results suggest that C5 and C5AR1 do not seem to be involved in the pathogenesis of IgAV.

References: [1] Arthritis Rheum. 2013 Jan;65(1):1-11, [2] Front Immunol. 2022 Oct 3:13:921864, [3] Autoimmun Rev. 2017 Dec;16(12):1246-1253, [4] Immunobiology. 2023 Sep;228(5):152413.
Research funded by FEDER funds (EU) and “Fondo de Investigaciones Sanitarias” (ISCIII, Health Ministry, Spain), grant number PI21/00042. JCBL: PFIS program fellowship (ISCIII-ESF: FI22/00020); RL-M: Miguel Servet type II (ISCIII-ESF: CPII21/00004).

Supporting image 1

Genotype and allele frequencies

Supporting image 2

Haplotype frequencies

Disclosures: J. Batista-Liz: None; V. Calvo-Rio: AstraZeneca, 6, GlaxoSmithKlein(GSK), 6, Janssen, 6, otsuka, 6; M. Sebastián Mora-Gil: None; L. Gabrie-Rodriguez: None; R. Gálvez Sánchez: None; B. Sevilla-Pérez: None; J. Callejas: None; M. Leonardo: None; A. Peñalba: None; J. Narvaez-García: None; L. Martín-Penagos: None; L. Caminal-Montero: None; P. COLLADO: None; P. Quiroga Colina: None; E. Vicente-rabaneda: None; E. Rubio: None; M. León Luque: None; J. Blanco-Madrigal: None; E. Galindez-Agirregoikoa: AbbVie/Abbott, 6, Amgen, 6, Eli Lilly, 6, Janssen, 6, Novartis, 6, Pfizer, 6, UCB, 6; S. Castañeda: Bristol-Myers Squibb(BMS), 2, 6, Eli Lilly, 2, 6, Merck/MSD, 2, 5, 6, Pfizer, 5, Roche, 2, 6, UCB, 2, 5; R. Blanco-Alonso: AbbVie, 2, 5, 6, Bristol-Myers Squibb, 2, 6, Galapagos, 6, Janssen, 2, 6, Lilly, 2, 6, MSD, 2, 5, 6, Pfizer, 2, 6, Roche, 2, 5, 6; V. Pulito-Cueto: None; R. Lopez-mejias: None.

To cite this abstract in AMA style:

Batista-Liz J, Calvo-Rio V, Sebastián Mora-Gil M, Gabrie-Rodriguez L, Gálvez Sánchez R, Sevilla-Pérez B, Callejas J, Leonardo M, Peñalba A, Narvaez-García J, Martín-Penagos L, Caminal-Montero L, COLLADO P, Quiroga Colina P, Vicente-rabaneda E, Rubio E, León Luque M, Blanco-Madrigal J, Galindez-Agirregoikoa E, Castañeda S, Blanco-Alonso R, Pulito-Cueto V, Lopez-mejias R. C5 Signaling Pathway Genes as Key Drivers of the Pathogenesis of IgA Vasculitis? [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/c5-signaling-pathway-genes-as-key-drivers-of-the-pathogenesis-of-iga-vasculitis/. Accessed .

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