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

S. H. Jiang; S. Mercan; I. Papa; M. Moldovan; G. D. Walters; M. Koina; M. Fadia; M. Stanley; T. Lea-Henry; A. Cook; J. Ellyard; B. McMorran; M. Sundaram; Russell Thomson; P. F. Canete; W. Hoy; H. Hutton; M. Srivastava; K. McKeon; I. Rua Figueroa; R. Cervera; R. Faria; S. D'Alfonso; M. Gatto; V. Athanasopoulos; M. Field; J. Mathews; E. Cho; T. D. Andrews; A. R. Kitching; M. C. Cook; M. A. Riquelme; M. Bahlo; C. G. Vinuesa

doi:10.1016/j.xcrm.2021.100475

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

S. H. Jiang, S. Mercan, I. Papa, M. Moldovan, G. D. Walters, M. Koina, M. Fadia, M. Stanley, T. Lea-Henry, A. Cook, J. Ellyard, B. McMorran, M. Sundaram, Russell Thomson, P. F. Canete, W. Hoy, H. Hutton, M. Srivastava, K. McKeon, I. Rua FigueroaR. Cervera, R. Faria, S. D'Alfonso, M. Gatto, V. Athanasopoulos, M. Field, J. Mathews, E. Cho, T. D. Andrews, A. R. Kitching, M. C. Cook, M. A. Riquelme, M. Bahlo, C. G. Vinuesa

Western Sydney University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	100475
Number of pages	10
Journal	Cell Reports Medicine
Volume	2
Issue number	12
DOIs	https://doi.org/10.1016/j.xcrm.2021.100475
Publication status	Published - 2021

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Jiang, S. H., Mercan, S., Papa, I., Moldovan, M., Walters, G. D., Koina, M., Fadia, M., Stanley, M., Lea-Henry, T., Cook, A., Ellyard, J., McMorran, B., Sundaram, M., Thomson, R., Canete, P. F., Hoy, W., Hutton, H., Srivastava, M., McKeon, K., ... Vinuesa, C. G. (2021). Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease. Cell Reports Medicine, 2(12), Article 100475. https://doi.org/10.1016/j.xcrm.2021.100475

@article{586a92e85dc54bda9f91f27e3af2db62,

title = "Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease",

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.",

author = "Jiang, {S. H.} and S. Mercan and I. Papa and M. Moldovan and Walters, {G. D.} and M. Koina and M. Fadia and M. Stanley and T. Lea-Henry and A. Cook and J. Ellyard and B. McMorran and M. Sundaram and Russell Thomson and Canete, {P. F.} and W. Hoy and H. Hutton and M. Srivastava and K. McKeon and {Rua Figueroa}, I. and R. Cervera and R. Faria and S. D'Alfonso and M. Gatto and V. Athanasopoulos and M. Field and J. Mathews and E. Cho and Andrews, {T. D.} and Kitching, {A. R.} and Cook, {M. C.} and Riquelme, {M. A.} and M. Bahlo and Vinuesa, {C. G.}",

year = "2021",

doi = "10.1016/j.xcrm.2021.100475",

language = "English",

volume = "2",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "12",

}

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, Rua 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 2021, 'Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease', Cell Reports Medicine, vol. 2, no. 12, 100475. https://doi.org/10.1016/j.xcrm.2021.100475

TY - JOUR

T1 - Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease

AU - Jiang, S. H.

AU - Mercan, S.

AU - Papa, I.

AU - Moldovan, M.

AU - Walters, G. D.

AU - Koina, M.

AU - Fadia, M.

AU - Stanley, M.

AU - Lea-Henry, T.

AU - Cook, A.

AU - Ellyard, J.

AU - McMorran, B.

AU - Sundaram, M.

AU - Thomson, Russell

AU - Canete, P. F.

AU - Hoy, W.

AU - Hutton, H.

AU - Srivastava, M.

AU - McKeon, K.

AU - Rua Figueroa, I.

AU - Cervera, R.

AU - Faria, R.

AU - D'Alfonso, S.

AU - Gatto, M.

AU - Athanasopoulos, V.

AU - Field, M.

AU - Mathews, J.

AU - Cho, E.

AU - Andrews, T. D.

AU - Kitching, A. R.

AU - Cook, M. C.

AU - Riquelme, M. A.

AU - Bahlo, M.

AU - Vinuesa, C. G.

PY - 2021

Y1 - 2021

N2 - 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.

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.

UR - https://hdl.handle.net/1959.7/uws:77530

U2 - 10.1016/j.xcrm.2021.100475

DO - 10.1016/j.xcrm.2021.100475

M3 - Article

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 12

M1 - 100475

ER -

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

Abstract

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