AB0145 IgA VASCULITIS AND IgA NEPHROPATHY SHARE A SIMILAR IL33-IL1RL1 ASSOCIATION PATTERN

Abstract

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.