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BackgroundIgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions [1, 2], that share pathogenic mechanisms [1], in which B-lymphocytes are described as key cells implicated in these processes. BAFF, APRIL and BAFF-R are cytokines implicated in the development of B-lymphocytes [3, 4] and in autoimmune processes [5, 6]. In this regard, an influence of BAFF, APRIL and BAFFR polymorphisms was observed on several immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion variant for inflammatory conditions [7, 8].ObjectivesTo determine whether BAFF, APRIL and BAFFR could be used as differential biomarkers between IgAV and IgAN.MethodsBAFF rs374039502 (which colocalizes with BAFF GCTGT>A), two tag variants within APRIL (rs11552708 and rs6608) and two tag variants within BAFFR (rs7290134 and rs77874543) were genotyped in 394 Caucasian IgAV patients, 95 patients with IgAN and 832 matched healthy controls.ResultsSimilar genotype and allele frequencies were observed in the whole cohort of patients with IgAV when compared to those with IgAN when BAFF, APRIL and BAFFR variants were analyzed independently (Table 1). In accordance with that, no BAFF, APRIL and BAFFR genotype or allele differences were detected between IgAV patients who developed nephritis and patients with IgAN (Table 1). Additionally, no statistically significant differences were observed between the whole cohort of patients with IgAV and healthy controls as well as between patients with IgAN and healthy controls when each when BAFF, APRIL and BAFFR genetic variant was also analyzed independently (Table 1). Similar results were disclosed when haplotype frequencies of APRIL and BAFFR were compared between the different comparative groups above mentioned (data not shown).Table 1.Genotype and allele frequencies of BAFF, APRIL and BAFFR in the whole cohort of patients with IgAV, patients with IgAV who developed nephritis, patients with IgAN and healthy controls.PolymorphismChangeData setGenotypes, % (n)Alleles, % (n)1/21/11/22/212BAFF rs374039502T/AIgAV92.1 (363)7.9 (31)0.096.1 (757)3.9 (31)IgAV with nephritis90.1 (128)9.9 (14)0.095.1 (270)4.9 (14)IgAN91.6 (87)8.4 (8)0.095.8 (182)4.2 (8)Controls91.8 (764)7.8 (65)0.4 (3)95.7 (1593)4.3 (71)APRIL rs11552708G/AIgAV78.7 (310)20.1 (79)1.3 (5)88.7 (699)11.3 (89)IgAV with nephritis81.1 (116)18.9 (27)0.090.6 (259)9.4 (27)IgAN75.8 (72)23.2 (22)1.1 (1)87.4 (166)12.6 (24)Controls78.7 (655)19.7 (164)1.6 (13)88.6 (1474)11.4 (190)APRIL rs6608C/TIgAV72.6 (286)25.4 (100)2.0 (8)85.3 (672)14.7 (116)IgAV with nephritis75.5 (108)23.1 (33)1.4 (2)87.1 (249)12.9 (37)IgAN65.3 (62)30.5 (29)4.2 (4)80.5 (153)19.5 (37)Controls71.0 (591)26.6 (221)2.4 (20)84.3 (1403)15.7 (261)BAFFR rs7290134A/GIgAV58.9 (232)35.5 (140)5.6 (22)76.6 (604)23.4 (184)IgAV with nephritis60.1 (86)32.2 (46)7.7 (11)76.2 (218)23.8 (68)IgAN57.9 (55)38.9 (37)3.2 (3)77.4 (147)22.6 (43)Controls58.7 (488)35.1 (292)6.3 (52)76.2 (1268)23.8 (396)BAFFR rs77874543G/CIgAV83.2 (328)15.5 (61)1.3 (5)91.0 (717)9.0 (71)IgAV with nephritis83.1 (118)16.9 (24)0.091.5 (260)8.5 (24)IgAN86.3 (82)13.7 (13)0.093.2 (167)6.8 (13)Controls83.7 (696)16.0 (133)0.4 (3)91.6 (1525)8.4 (139)IgAV: IgA vasculitis; IgAN: IgA nephropathy.ConclusionOur results reveal a similar BAFF, APRIL and BAFFR genetic distribution in IgAV and IgAN, suggesting that these genes could not be used as differential biomarkers between these pathologies.References[1]N Engl J Med 2013;368:2402-14;[2]Am J Kidney Dis 1988;12:373-7;[3]J Exp Med 1999;189:1747-56;[4]Nat Genet 2005;37:793-4;[5]Arthritis Res Ther 2018;20:158;[6]Arthritis Res Ther 2020;22:157;[7]Engl J Med 2017;376:1615-26;[8]Sci Rep 2018;8:8195.AcknowledgementsThis study was supported by the European Regional Development Fund (ERDF) and “Fondo de Investigaciones Sanitarias” (grant PI18/00042 and PI21/00042) 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 ERDF [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; RL-M is a recipient of a Miguel Servet type II programme fellowship from the ISCIII, co-funded by ESF `Investing in your future´ [grant number CPII21/00004].Disclosure of InterestsDiana Prieto-Peña: None declared, Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda Fillloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Diego de Argila: None declared, Esther F. Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Oreste Gualillo: 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: Abbvie, MSD, Jansen, and Roche, Grant/research support from: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Raquel López-Mejías: None declared

BackgroundIgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions that share pathogenic and molecular mechanisms [1] and may represent different outcomes of a continuous spectrum of the disease [2]. Interleukin (IL)-33 is a cytokine that exerts its biological functions by binding to its receptor, IL-1 receptor like 1 (IL-1RL1) [3]. Several lines of evidence demonstrate that genetic variants located both in IL33 and IL1RL1 genes are implicated in the increased risk of numerous immune-mediated diseases [4].ObjectivesTo determine whether IgAV and IgAN exhibit a different IL33-IL1RL1 association pattern.MethodsThree tag genetic variants within IL33 (rs3939286, rs7025417 and rs7044343) and three tag polymorphisms within IL1RL1 (rs2310173, rs13015714 and rs2058660), which cover the major variability of these loci and that were previously associated with several inflammatory diseases were genotyped in 380 Caucasian patients with IgAV, 96 patients with IgAN and 845 sex and ethnically matched healthy controls.ResultsSimilar genotype and allele frequencies were observed in the whole cohort of patients with IgAV when compared to those with IgAN when IL33-IL1RL1 genetic variants were analyzed independently (Table 1). In accordance with that, no IL33-IL1RL1 genotype or allele differences were detected between IgAV patients who developed nephritis and patients with IgAN (Table 1). Additionally, no statistically significant differences between the whole cohort of patients with IgAV and healthy controls as well as between patients with IgAN and healthy controls were observed when each IL33-IL1RL1 genetic variant was also analyzed independently (Table 1). Similar results were disclosed when haplotype frequencies were compared between the different comparative groups above mentioned (data not shown).Table 1.Genotype and allele frequencies of IL33 and IL1RL1 in the whole cohort of patients with IgAV, patients with IgAV who developed nephritis, patients with IgAN and healthy controls.PolymorphismChangeData setGenotypes, % (n)Alleles, % (n)1/21/11/22/212IL33 rs3939286C/TIgAV49.1 (186)40.9 (155)10.0 (38)69.5 (527)30.5 (231)IgAV with nephritis48.5 (66)39.7 (54)11.8 (16)68.4 (186)31.6 (86)IgAN43.8 (42)49.0 (47)7.3 (7)68.2 (131)31.8 (61)Controls49.0 (414)41.4 (350)9.6 (81)69.7 (1178)30.3 (512)IL33 rs7025417T/CIgAV68.1 (254)29.5 (110)2.4 (9)82.8 (618)17.2 (128)IgAV with nephritis69.9 (93)27.1 (36)3.0 (4)83.5 (222)16.5 (44)IgAN61.5 (59)37.5 (36)1.0 (1)80.2 (154)19.8 (38)Controls70.8 (598)25.9 (219)3.3 (28)83.7 (1415)16.3 (275)IL33 rs7044343T/CIgAV42.3 (160)42.1 (159)15.6 (59)63.4 (479)36.6 (277)IgAV with nephritis44.5 (61)39.4 (54)16.1 (22)64.2 (176)35.8 (98)IgAN40.6 (39)49.0 (47)10.4 (10)65.1 (125)34.9 (67)Controls44.5 (376)43.9 (371)11.6 (98)66.4 (1123)33.6 (567)IL1RL1 rs2310173G/TIgAV29.2 (111)46.1 (175)24.7 (94)52.2 (397)47.8 (363)IgAV with nephritis32.1 (44)43.1 (59)24.8 (34)53.6 (147)46.4 (127)IgAN20.8 (20)46.9 (45)32.3 (31)44.3 (85)55.7 (107)Controls30.2 (255)46.7 (395)23.1 (195)53.6 (905)46.4 (785)IL1RL1 rs13015714T/GIgAV56.3 (211)39.5 (148)4.3 (16)76.0 (570)24.0 (180)IgAV with nephritis61.8 (84)33.8 (46)4.4 (6)78.7 (214)21.3 (58)IgAN54.2 (52)40.6 (39)5.2 (5)74.5 (143)25.5 (49)Controls57.2 (483)37.2 (314)5.7 (48)75.7 (1280)24.3 (410)IL1RL1 rs2058660A/GIgAV56.9 (215)38.6 (146)4.5 (17)76.2 (576)23.8 (180)IgAV with nephritis62.2 (84)31.9 (43)5.9 (8)78.1 (211)21.9 (59)IgAN53.1 (51)42.7 (41)4.2 (4)74.5 (143)25.5 (49)Controls56.7 (479)37.5 (317)5.8 (49)75.4 (1275)24.6 (415)IgAV: IgA vasculitis; IgAN: IgA nephropathy.ConclusionOur results reveal that IgAV and IgAN share a similar IL33-IL1RL1 association pattern.References[1]N Engl J Med 2013;368:2402-14;[2]Am J Kidney Dis 1988;12:373-7;[3]J Immunol 2007;179:2551–5,[4]Sci Rep 2021;11:16163AcknowledgementsThis study was supported by the European Regional Development Fund (ERDF) and “Fondo de Investigaciones Sanitarias” (grant PI18/00042 and PI21/00042) 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 ERDF [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; RL-M is a recipient of a Miguel Servet type II programme fellowship from the ISCIII, co-funded by ESF `Investing in your future´ [grant number CPII21/00004].Disclosure of InterestsDiana Prieto-Peña: None declared, 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, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda Fillloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Patricia Quiroga Colino: None declared, Javier Sanchez Perez: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Oreste Gualillo: 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: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Grant/research support from: Abbvie, MSD, Jansen and Roche, Raquel López-Mejías: None declared

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.PolymorphismLocus1/2Data set1/11/22/212rs374039502BAFFT/APatients91.9 (353)8.1 (31)095.9 (737)4.1 (31)Controls91.5 (733)8.1 (65)0.4 (3)95.6 (1531)4.4 (71)rs11552708APRILG/APatients78.1 (299)20.6 (79)1.3 (5)88.4 (677)11.6 (89)Controls77.9 (625)20.4 (1641.6 (13)88.1 (1414)11.9 (190)rs6608APRILC/TPatients71.9 (277)26.0 (100)2.1 (8)84.9 (654)15.1 (116)Controls70.0 (561)27.6 (221)2.5 (20)83.7 (1343)16.3 (261)rs7290134BAFFRA/GPatients58.0 (224)36.3 (140)5.7 (22)76.2 (588)23.8 (184)Controls57.2 (459)36.4 (292)6.5 (52)75.3 (1210)24.6 (396)rs77874543BAFFRG/CPatients82.7 (316)16.0 (61)1.3 (5)90.7 (693)9.3 (71)Controls83.0 (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

Background:IgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions that share pathogenic and molecular mechanisms [1] and may represent different outcomes of a continuous spectrum of disease [2]. Interleukin (IL)17A has been identified as a common genetic risk locus for several immune-mediated diseases [3, 4].Objectives:To determine whether IgAV and IgAN exhibit a different IL17A association pattern.Methods:Five IL17A tag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were genotyped in 388 Caucasian patients with IgAV, 99 patients with IgAN and 1,003 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and healthy controls and between patients with IgAN and healthy controls were observed when each IL17A genetic variant was analyzed independently (Table 1). Similarly, IgAV patients exhibited similar genotype and allele IL17A frequencies than those with IgAN (Table 1). Moreover, no genotype or allele differences between IgAV patients who developed nephritis and patients with IgAN were detected. Furthermore, haplotype frequencies were similar in patients with IgAV, IgAV and nephritis and those with IgAN.Table 1.Genotype and allele frequencies of IL17A gene in patients with IgA vasculitis, patients with IgA nephropathy and healthy controls.PolymorphismChangeData set1/11/22/212rs4711998G/AIgAV53.4 (207)38.9 (151)7.7 (30)72.8 (565)27.2 (211)IgAN49.0 (48)42.9 (42)8.2 (8)70.4 (138)29.6 (58)Controls52.7 (529)41.2 (413)6.1 (61)73.3 (1471)26.7 (535)rs8193036T/CIgAV57.0 (221)38.4 (149)4.6 (18)76.2 (591)23.8 (185)IgAN64.3 (63)31.6 (31)4.1 (4)80.1 (157)19.9 (39)Controls60.3 (605)35.2 (353)4.5 (45)77.9 (1563)22.1 (443)rs3819024A/GIgAV44.1 (171)43.3 (168)12.6 (49)65.7 (510)34.3 (266)IgAN39.4 (39)54.5 (54)6.1 (6)66.7 (132)33.3 (66)Controls45.6 (457)44.6 (447)9.9 (99)67.8 (1361)32.2 (645)rs2275913G/AIgAV44.6 (172)43.3 (167)12.2 (47)66.2 (511)33.8 (261)IgAN39.8 (39)53.1 (52)7.1 (7)66.3 (130)33.7 (66)Controls44.8 (449)44.2 (443)11.1 (111)66.8 (1341)33.2 (665)rs7747909G/AIgAV53.9 (209)39.4 (153)6.7 (26)73.6 (571)26.4 (205)IgAN41.1 (39)54.7 (52)4.2 (4)68.4 (130)31.6 (60)Controls53.0 (532)39.4 (395)7.6 (76)72.7 (1459)27.3 (547)Conclusion:Our results revealed that IgAV and IgAN share a similar IL17A association pattern.References:[1]N Engl J Med 2013;368:2402-14.[2]Am J Kidney Dis 1988;12:373-7.[3]Ann Rheum Dis 2014;73:1742-5.[4]Mediators Inflamm 2018;2018:1395823.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: None declared, Fernanda Genre: None declared, Sara Remuzgo Martinez: 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, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: 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

Background:Interferon signaling pathway plays a relevant role in autoimmunity. Genetic variants in theinterferon regulatory factor (IRF) 5gene, that encodes the major regulator of the type I interferon induction [1], have been related to the development of several inflammatory diseases [2].Objectives:To determine the influence ofIRF5on Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular disease.Methods:ThreeIRF5polymorphisms (rs2004640, rs2070197 and rs10954213) representative of 3 different haplotype blocks were genotyped in 372 Caucasian patients with IgAV and 876 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and controls were observed when eachIRF5polymorphism was analyzed independently. Similarly, no statistically significant differences between patients with IgAV and controls were found whenIRF5polymorphisms were evaluated combined conforming haplotypes. Additionally, there were no statistically significant differences in genotype, allele and haplotype frequencies ofIRF5when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations.Conclusion:Our results do not support an influence ofIRF5on the pathogenesis of IgAV.References:[1]Nat Immunol 2011; 12: 231-8;[2]Arthritis Res Ther 2014; 16: R146.Acknowledgments: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). 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 CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF).Disclosure of Interests:Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Verónica Pulito-Cueto: None declared, D. Prieto-Peña: 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, María Jesús Cabero: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, Antonio Navas Parejo: None declared, Javier Sanchez Perez: None declared, Maximiliano Aragües: None declared, Esteban Rubio: 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 Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared

Background:Cytokines signaling pathway genes represent a key component of the genetic network implicated in the pathogenesis of Immunoglobulin-A vasculitis (IgAV) [1], an inflammatory vascular pathology.Interleukin (IL)17Ais a genetic risklocusfor autoimmune diseases, such as giant cell arteritis [2] and spondyloarthritis [3].Objectives:To determine the potential influence ofIL17Aon IgAV.Methods:FiveIL17Atag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were genotyped in 360 Caucasian patients with IgAV and 1,003 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and healthy controls were observed when eachIL17Agenetic variant was analyzed independently. Similarly, no statistically significant differences between patients with IgAV and healthy controls were found when the fiveIL17Apolymorphisms were evaluated combined conforming haplotypes. In addition, there were no statistically significant differences in genotype, allele and haplotype frequencies ofIL17Awhen patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations.Conclusion:Our results do not support an influence ofIL17Aon the pathogenesis of IgAV.References:[1]Autoimmun Rev 2018; 17: 301-15[2]Ann Rheum Dis 2014; 73: 1742-5[3]Mediators Inflamm 2018; 2018: 1395823.Acknowledgments: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). 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 CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF).Disclosure of Interests:Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, D. Prieto-Peña: 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, María Jesús Cabero: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, Antonio Navas Parejo: None declared, Diego de Argila: None declared, Maximiliano Aragües: 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 Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared