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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