Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease

Jiang, SH; Mercan, S; Papa, I; Moldovan, M; Walters, GD; Koina, M; Fadia, M; Stanley, M; Lea-Henry, T; Cook, A; Ellyard, J; McMorran, B; Sundaram, M; Thomson, R; Canete, PF; Hoy, W; Hutton, H; Srivastava, M; McKeon, K; de la R&#250;a Figueroa, I; Cervera, R; Faria, R; D&#39;Alfonso, S; Gatto, M; Athanasopoulos, V; Field, M; Mathews, J; Cho, E; Andrews, TD; Kitching, AR; Cook, MC; Riquelme, MA; Bahlo, M; Vinuesa, CG

Author(s): Jiang, SH; Mercan, S; Papa, I; Moldovan, M; Walters, GD; Koina, M; Fadia, M; Stanley, M; Lea-Henry, T; Cook, A; Ellyard, J; McMorran, B; Sundaram, M; Thomson, R; Canete, PF; Hoy, W; Hutton, H; Srivastava, M; McKeon, K; de la Rúa Figueroa, I; Cervera, R; Faria, R; D'Alfonso, S; Gatto, M; Athanasopoulos, V; Field, M; Mathews, J; Cho, E; Andrews, TD; Kitching, AR; Cook, MC; Riquelme, MA; Bahlo, M; Vinuesa, CG;
Details: Publication Year 2021-12-21,Volume 2,Issue #12,Page 100475
Journal Title: Cell Reports Medicine
Abstract: We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.(1) (,) (2) We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1 (+/-) mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE.
Publisher: Cell Press
Keywords: antibody; autoimmune; chronic kidney disease; genetic; glomerulonephritis; immunoglobulin; lupus nephritis
Research Division(s): Population Health And Immunity
PubMed ID: 35028616
Publisher's Version: https://doi.org/10.1016/j.xcrm.2021.100475
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2022-02-07 10:12:18

Last Modified: 2022-02-08 11:37:05