BAFF-APRIL-BAFFR PATHWAY ON THE PATHOGENESIS OF IMMUNOGLOBULIN-A VASCULITIS

Background: BAFF, APRIL and BAFFR are genes that encode cytokines with a key role in the development and survival of B-lymphocytes [1-4]: The B cell-activating factor (BAFF, also known as BLyS), a proliferation-inducing ligand (APRIL) and BAFF receptor (BAFF-R), respectively. Previous genetic studies have revealed that the BAFF-APRIL-BAFFR pathway is implicated in the genetic predisposition to several immune-mediated diseases [5]. Objectives: To determine whether the BAFF-APRIL-BAFFR pathway represents a novel genetic risk factor for the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory disease in which IgA deposits and B-lymphocytes are crucial [6, 7]. Methods: A functional BAFF polymorphism (rs374039502) and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients (the largest series of Caucasian patients with IgAV ever assessed for genetic studies) and 806 sex and ethnically matched healthy controls by TaqMan assays. Results: No statistically significant differences in the genotype and allele frequencies between patients with IgAV and healthy controls were observed when each genetic variant of BAFF APRIL and BAFFR was analyzed independently ( Table 1 ). Likewise, no statistically significant differences in genotype and allele frequencies of BAFF APRIL or BAFFR were found when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Similar results were disclosed when haplotype frequencies of APRIL and BAFFR were compared between patients with IgAV and healthy controls as well as patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Conclusion: Our results suggest that the BAFF-APRIL-BAFFR pathway does not contribute to the genetic network underlying IgAV. REFERENCES: [1]J Exp Med 1999;190:1697-710; [2] Science 1999;285:260-3; [3] Nat Genet 2005;37:829-34; [4] Nat Immunol 2002;3:822-9; [5] N Engl J Med 2017;376:1615-26; [6] N Engl J Med 2013;368:2402-14; [7] Autoimmun Rev 2018;17:301-315. Table 1. Genotype and allele frequencies of BAFF, APRIL and BAFFR genes in patients with IgA vasculitis and healthy controls. Polymorphism Locus 1/2 Data set 1/1 1/2 2/2 1 2 rs374039502 BAFF T/A Patients 91.9 (353) 8.1 (31) 0 95.9 (737) 4.1 (31) Controls 91.5 (733) 8.1 (65) 0.4 (3) 95.6 (1531) 4.4 (71) rs11552708 APRIL G/A Patients 78.1 (299) 20.6 (79) 1.3 (5) 88.4 (677) 11.6 (89) Controls 77.9 (625) 20.4 (164 1.6 (13) 88.1 (1414) 11.9 (190) rs6608 APRIL C/T Patients 71.9 (277) 26.0 (100) 2.1 (8) 84.9 (654) 15.1 (116) Controls 70.0 (561) 27.6 (221) 2.5 (20) 83.7 (1343) 16.3 (261) rs7290134 BAFFR A/G Patients 58.0 (224) 36.3 (140) 5.7 (22) 76.2 (588) 23.8 (184) Controls 57.2 (459) 36.4 (292) 6.5 (52) 75.3 (1210) 24.6 (396) rs77874543 BAFFR G/C Patients 82.7 (316) 16.0 (61) 1.3 (5) 90.7 (693) 9.3 (71) Controls 83.0 (666) 16.6 (133) 0.4 (3) 91.3 (1465) 8.7 (139) Acknowledgements: This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by the European Regional Development Fund (ERDF) [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud; LL-G is supported by funds of IDIVAL [grant number INNVAL20/06]; RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CP16/00033]. Disclosure of Interests: Diana Prieto-Peña Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Leticia Lera-Gómez: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, J. Narváez: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Javier Sanchez Perez: None declared, Diego de Argila: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galindez: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 267Session: Translating vasculitis (Poster Tours)