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Vasculitis, small and medium size vessels
POS1007 THE INVOLVEMENT OF THE C5 AND C5AR1 GENES IN THE PATHOGENESIS OF IgAV
  1. J. C. Batista-Liz1,
  2. V. Calvo-Río1,2,
  3. M. Sebastián Mora-Gil1,
  4. B. Sevilla-Pérez3,
  5. J. L. Callejas4,5,
  6. M. T. Leonardo6,
  7. A. Peñalba6,
  8. M. J. Cabero6,
  9. J. Narváez7,
  10. L. Martín-Penagos1,8,
  11. L. Belmar-Vega1,8,
  12. C. Gomez-Fernandez1,9,
  13. L. Caminal-Montero10,11,
  14. P. Collado12,
  15. P. Quiroga Colina13,
  16. E. Vicente-Rabaneda13,
  17. E. Rubio-Romero14,
  18. M. León Luque14,
  19. J. M. Blanco-Madrigal15,
  20. E. Galíndez-Agirregoikoa15,
  21. S. Castañeda13,
  22. R. Blanco1,2,
  23. V. Pulito-Cueto1,
  24. R. López-Mejías1
  1. 1IDIVAL, Immunopathology Group, Santander, Spain
  2. 2Hospital Universitario Marqués de Valdecilla, Rheumatology Department, Santander, Spain
  3. 3Hospital Universitario Clínico San Cecilio, Division of Pediatrics, Granada, Spain
  4. 4Hospital Universitario Clínico San Cecilio, Systemic Autoimmune Disease Unit, Granada, Spain
  5. 5Instituto de Investigación Biosanitaria Ibs.GRANADA, Granada, Spain
  6. 6Hospital Universitario Marqués de Valdecilla, Division of Pediatrics, Santander, Spain
  7. 7Hospital Universitario de Bellvitge, Rheumatology Department, Barcelona, Spain
  8. 8Hospital Universitario Marqués de Valdecilla, Division of Nephrology, Santander, Spain
  9. 9Hospital Universitario Marqués de Valdecilla, Division of Dermatology, Santander, Spain
  10. 10Hospital Universitario Central de Asturias, Internal Medicine Department, Oviedo, Spain
  11. 11Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
  12. 12Hospital Universitario Severo Ochoa, Division of Rheumatology, Madrid, Spain
  13. 13Hospital Universitario de La Princesa, Division of Rheumatology, Madrid, Spain
  14. 14Hospital Universitario Virgen del Rocío, Division of Rheumatology, Sevilla, Spain
  15. 15Hospital Universitario de Basurto, Division of Rheumatology, Bilbao, Spain

Abstract

Background: 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]. It has been shown that these immunocomplexes activate the mannan-binding lectin and the alternative complement pathway [2]. Moreover, the presence of complement system components has been observed in skin and kidney biopsies in IgAV patients [3]. In this context, C5a (a protein fragment cleaved from 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.

Objectives: The aim of this work was 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 723 healthy ethnically matched controls, were recruited for this study. Among the IgAV patients, 117 presented nephritis (IgAVN). Eight tag single nucleotide polymorphisms (SNPs) within C5 (rs10760128, rs74971050, rs4310279, rs7868761, rs10818495, rs10156396, rs3815467, and rs16910280) and 3 C5AR1 tag SNPs (rs10853784, rs11673071, and rs11670789) were genotyped 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 healthy controls (HC) (Table 1). Likewise, no statistically significant differences were observed in genotype and allele frequencies of C5 and C5AR1 when IgAV patients were stratified according to the severity of the disease, represented by the presence or absence of renal manifestations (Table 1). In addition, no statistically significant differences were shown among IgAV patients stratified according to other clinical aspects, such as the age at disease onset or the presence/absence of articular and gastrointestinal manifestation in C5 and C5AR1 (Data not shown). Furthermore, no differences in the haplotype frequencies of C5 and C5AR1 were observed between IgAV patients and HC (Table 2), and between stratified IgAV patients according to the severity of the disease (Table 2) as well as to other clinical manifestations (Data not shown).

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.

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Acknowledgements: This research was funded by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain), grant number PI18/00042 and PI21/00042. JCB-L is a recipient of a PFIS programme fellowship from the ISCIII, co-funded by the European Social Fund (“Investing in your future”), grant number FI22/00020.VC-R is a recipient of a grant for research activity intensification provided by the Spanish Rhemathology Foundation. MSM-G is supported by funds of “Fondo de Investigaciones Sanitarias” from ISCIII, grant number PI18/00042.VP-C is supported by funds of IDIVAL, grant number NVAL23/02. RL-M is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF (“Investing in your future”), grant number CPII21/00004.

Disclosure of Interests: Joao Carlos Batista-Liz: None declared, Vanesa Calvo-Río Abbvie, Lilly, Grünenthal, AMGEN. MSD, Novartis, Galapagos, Vifor, GSK, and Otsuka, María Sebastián Mora-Gil: None declared, Belén Sevilla-Pérez: None declared, José Luis Callejas: None declared, María Teresa Leonardo: None declared, Ana Peñalba: None declared, María Jesús Cabero: None declared, Javier Narváez: None declared, Luis Martín-Penagos: None declared, Lara Belmar-Vega: None declared, Cristina Gomez-Fernandez: None declared, Luis Caminal-Montero: None declared, Paz Collado: None declared, Patricia Quiroga Colina: None declared, Esther Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, Manuel León Luque: None declared, Juan María Blanco-Madrigal: None declared, Eva Galíndez-Agirregoikoa: 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, Verónica Pulito-Cueto: None declared, Raquel López-Mejías: None declared.

  • Innate immunity
  • Biomarkers
  • Genetics

https://doi.org/10.1136/annrheumdis-2024-eular.381

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