RT Journal Article
T1 Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease
A1 Jiang, Simon H.
A1 Mercan, Sevcan
A1 Papa, Ilenia
A1 Moldovan, Max
A1 Walters, Giles D.
A1 Koina, Mark
A1 Fadia, Mitali
A1 Stanley, Maurice
A1 Lea-Henry, Tom
A1 Cook, Amelia
A1 Ellyard, Julia
A1 McMorran, Brendan
A1 Sundaram, Madhivanan
A1 Thomson, Russell
A1 Canete, Pablo F.
A1 Hoy, Wendy
A1 Hutton, Holly
A1 Srivastava, Monika
A1 McKeon, Kathryn
A1 de la Rua Figueroa, Inigo
A1 Cervera, Ricard
A1 Faria, Raquel
A1 D'Alfonso, Sandra
A1 Gatto, Mariele
A1 Athanasopoulos, Vicki
A1 Field, Matthew
A1 Mathews, John
A1 Cho, Eun
A1 Andrews, Thomas D.
A1 Kitching, A. Richard
A1 Cook, Matthew C.
A1 Alarcon Riquelme, Marta
A1 Bahlo, Melanie
A1 Vinuesa, Carola G.
K1 Systemic-lupus-erythematosus
K1 Susceptibility loci
K1 Renal-disease
K1 Genome-wide
K1 Association
K1 Nephritis
K1 Classification
K1 Mutations
K1 Gene
K1 Glomerulonephritis
AB 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.
PB Cell press
SN 2666-3791
YR 2021
FD 2021-12-21
LK https://hdl.handle.net/10668/28384
UL https://hdl.handle.net/10668/28384
LA en
DS RISalud
RD Apr 7, 2025