2370: C5 as a Genetic Marker for Discriminating Between IgA Vasculitis and IgA Nephropathy?

JOAO CARLOS BATISTA LIZ¹, Vanesa Calvo Río², María Sebastián Mora-Gil¹, Belén Sevilla-Pérez³, María Teresa Leonardo⁴, Ana Peñalba⁴, María Jesús Cabero⁴, Javier Narvaez⁵, luis martin penagos⁶, Emilio Rodrigo⁶, Lara Belmar-Vega⁶, Cristina Gomez-Fernandez⁷, Luis Caminal-Montero⁸, Paz Collado⁹, Antonio Fernandez-Nebro¹⁰, gisela Díaz-Cordovés¹¹, Maryia Nikitsina¹², Esther Vicente Rabaneda¹³, secundino Cigarrán¹⁴, jesús Calviño¹⁵, carmen cobelo¹⁵, Manuel León Luque¹⁶, Esteban Rubio¹⁶, Juan María Blanco-Madrigal¹⁷, Eva Galindez-Agirregoikoa¹⁸, Santos Castañeda¹⁹, Ricardo Blanco²⁰, Verónica Pulito-Cueto¹ and Raquel López-Mejías¹, ¹Rheumatology Department, Immunopathology Group, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain, ²Valdecilla Hospital, Santander, Spain, ³Division of Pediatrics, Hospital Universitario San Cecilio, Granada, Spain, ⁴Division of Pediatrics, Hospital Universitario Marqués de Valdecilla, Santander, Spain, ⁵Hospital Universitario de Bellvitge, Barcelona, Spain, ⁶Division of Nephrology, Immunopathology Group, Hospital Universitario Marqués de Valdecilla-DIVAL, Santander, Spain, ⁷Division of Dermatology,Immunopathology Group, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain, ⁸Internal Medicine Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain, ⁹Division of Rheumatology, Hospital Universitario Severo Ochoa, Madrid, Spain, ¹⁰Hospital Regional Universitario de Málaga, Malaga, Spain, ¹¹Division of Rheumatology, Hospital Regional Universitario Carlos Haya, Málaga, Spain, ¹²Division of Rheumatology, Hospital Universitario de La Princesa, Madrid, Spain, ¹³Rheumatology, Hospital Universitario de La Princesa, Madrid, Spain, ¹⁴Division of Nephrology, Hospital da Costa Burela, Lugo, Spain, ¹⁵Division of Nephrology, Hospital Universitario Lucus Augusti, Lugo, Spain, ¹⁶Division of Rheumatology, Hospital Universitario Virgen del Rocío, Sevilla, Spain, ¹⁷Division of Rheumatology, Hospital Universitario de Basurto, Bilbao, Spain, ¹⁸Basurto University Hospital, Bilbao, Spain, ¹⁹Hospital Universitario de la Princesa, Madrid, Spain, ²⁰Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain

Background/Purpose: Immunoglobulin-A vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions that share pathophysiological mechanisms^1,2. Similar features are also described between IgAV nephritis (IgAVN) and IgAN³. However, whether IgAV is an extension of IgAN or a different disease entity is still inconclusive³. The complement system plays a crucial role in the development of immune-mediated disorders, being specifically associated with renal pathology and clinical phenotypes in patients with IgAV⁴. In this regard, C5 signalling blockage is described as a novel strategy to modulate inflammatory diseases, such as different types of vasculitis⁵.

Methods: The main objective of this study was to determine the role of C5 as a potential genetic biomarker for discriminating between IgAV and IgAN. For that purpose, 9 tag genetic variants within C5 (rs10760128, rs74971050, rs4310279, rs7868761, rs10818495, rs2159777, rs10156396, rs3815467 and rs16910280) were genotyped in the largest series of Caucasian patients diagnosed with IgAV ever assessed for genetic studies (n=407) and in 98 Caucasian patients diagnosed with IgAN. 35.4% of our patients were IgAVN.

Results: Similar genotype distribution were observed in IgAV patients compared to those with IgAN, when C5variants were analyzed independently (Table 1). In addition, no statistically significant allele differences were disclosed between patients with IgAV patients and those with IgAN (Table 1). Moreover, when we compared patients with IgAVN and patients with IgAN, we did not observe genotype nor allele statistical differences (Table 1). Similar results were disclosed when haplotype frequencies of C5 were compared between patients with IgAV and those with IgAN, as well as between patients with IgAVNand patients with IgAN (data not shown).

Conclusion: Our results reveal a similar C5genetic distribution in IgAV, IgAVN and IgAN, indicating that this gene may not be used as a genetic biomarkerfor discriminating between these entities.

References: [1] N Engl J Med 2013;368:2402-14; [2] Autoimmun Rev 2018;17:301-15; [3] Front Immunol 2022;13:921864; [4] Front Immunol 2019;10:2166.

This research was funded by European Union FEDER funds and "Fondo de Investigaciones Sani-tarias" from "Instituto de Salud Carlos III" (ISCIII, Health Ministry, Spain), grant number PI18/00042 and PI21/00042. JCBL 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. MSM-G is supported by funds of IDIVAL, grant number TRANSVAL22/01.VP-C is supported by funds of "Fondo de Investigaciones Sanitarias" from ISCIII, grant number PI18/00042. 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.






J. BATISTA LIZ: None; V. Calvo Río: None; M. Sebastián Mora-Gil: None; B. Sevilla-Pérez: None; M. Teresa Leonardo: None; A. Peñalba: None; M. Cabero: None; J. Narvaez: None; l. martin penagos: None; E. Rodrigo: None; L. Belmar-Vega: None; C. Gomez-Fernandez: None; L. Caminal-Montero: None; P. Collado: None; A. Fernandez-Nebro: None; g. Díaz-Cordovés: None; M. Nikitsina: None; E. Vicente Rabaneda: None; s. Cigarrán: None; j. Calviño: None; c. cobelo: None; M. León Luque: None; E. Rubio: None; J. Blanco-Madrigal: None; E. Galindez-Agirregoikoa: None; S. Castañeda: None; R. Blanco: AbbVie, 5, 6, Amgen, 6, AstraZeneca, 2, BMS, 6, Eli Lilly, 6, Galapagos, 2, 6, Janssen, 2, 6, MSD, 6, Novartis, 2, 6, Pfizer, 2, 6, Roche, 5, 6, Sanofi, 6; V. Pulito-Cueto: None; R. López-Mejías: None.