Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells

Jin Li; Silje F. Jørgensen; S. Melkorka Maggadottir; Marina Bakay; Klaus Warnatz; Joseph Glessner; Rahul Pandey; Ulrich Salzer; Reinhold E. Schmidt; Elena Perez; Elena Resnick; Sigune Goldacker; Mary Buchta; Torsten Witte; Leonid Padyukov; Vibeke Videm; Trine Folseraas; Faranaz Atschekzei; James T. Elder; Rajan P. Nair; Juliane Winkelmann; Christian Gieger; Markus M. Nöthen; Carsten Büning; Stephan Brand; Kathleen E. Sullivan; Jordan S. Orange; Børre Fevang; Stefan Schreiber; Wolfgang Lieb; Pål Aukrust; Helen Chapel; Charlotte Cunningham-Rundles; Andre Franke; Tom H. Karlsen; Bodo Grimbacher; Hakon Hakonarson; Lennart Hammarström; Eva Ellinghaus

doi:10.1038/ncomms7804

Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells

Jin Li, Silje F. Jørgensen, S. Melkorka Maggadottir, Marina Bakay, Klaus Warnatz, Joseph Glessner, Rahul Pandey, Ulrich Salzer, Reinhold E. Schmidt, Elena Perez, Elena Resnick, Sigune Goldacker, Mary Buchta, Torsten Witte, Leonid Padyukov, Vibeke Videm, Trine Folseraas, Faranaz Atschekzei, James T. Elder, Rajan P. NairJuliane Winkelmann, Christian Gieger, Markus M. Nöthen, Carsten Büning, Stephan Brand, Kathleen E. Sullivan, Jordan S. Orange, Børre Fevang, Stefan Schreiber, Wolfgang Lieb, Pål Aukrust, Helen Chapel, Charlotte Cunningham-Rundles, Andre Franke, Tom H. Karlsen, Bodo Grimbacher, Hakon Hakonarson, Lennart Hammarström, Eva Ellinghaus

Lehrstuhl für Neurogenetik (2015 — 2023)

Publikation: Beitrag in Fachzeitschrift › Artikel › Begutachtung

57 Zitate (Scopus)

Abstract

Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10^-9) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10^-16). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.

Originalsprache	Englisch
Aufsatznummer	6804
Fachzeitschrift	Nature Communications
Jahrgang	6
DOIs	https://doi.org/10.1038/ncomms7804
Publikationsstatus	Veröffentlicht - 20 Apr. 2015

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Li, J., Jørgensen, S. F., Maggadottir, S. M., Bakay, M., Warnatz, K., Glessner, J., Pandey, R., Salzer, U., Schmidt, R. E., Perez, E., Resnick, E., Goldacker, S., Buchta, M., Witte, T., Padyukov, L., Videm, V., Folseraas, T., Atschekzei, F., Elder, J. T., ... Ellinghaus, E. (2015). Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells. Nature Communications, 6, Artikel 6804. https://doi.org/10.1038/ncomms7804

@article{46f9243614284afbb9bcea5abc3203cb,

title = "Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells",

abstract = "Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10-9) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10-16). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.",

author = "Jin Li and J{\o}rgensen, {Silje F.} and Maggadottir, {S. Melkorka} and Marina Bakay and Klaus Warnatz and Joseph Glessner and Rahul Pandey and Ulrich Salzer and Schmidt, {Reinhold E.} and Elena Perez and Elena Resnick and Sigune Goldacker and Mary Buchta and Torsten Witte and Leonid Padyukov and Vibeke Videm and Trine Folseraas and Faranaz Atschekzei and Elder, {James T.} and Nair, {Rajan P.} and Juliane Winkelmann and Christian Gieger and N{\"o}then, {Markus M.} and Carsten B{\"u}ning and Stephan Brand and Sullivan, {Kathleen E.} and Orange, {Jordan S.} and B{\o}rre Fevang and Stefan Schreiber and Wolfgang Lieb and P{\aa}l Aukrust and Helen Chapel and Charlotte Cunningham-Rundles and Andre Franke and Karlsen, {Tom H.} and Bodo Grimbacher and Hakon Hakonarson and Lennart Hammarstr{\"o}m and Eva Ellinghaus",

year = "2015",

month = apr,

day = "20",

doi = "10.1038/ncomms7804",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

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Li, J, Jørgensen, SF, Maggadottir, SM, Bakay, M, Warnatz, K, Glessner, J, Pandey, R, Salzer, U, Schmidt, RE, Perez, E, Resnick, E, Goldacker, S, Buchta, M, Witte, T, Padyukov, L, Videm, V, Folseraas, T, Atschekzei, F, Elder, JT, Nair, RP, Winkelmann, J, Gieger, C, Nöthen, MM, Büning, C, Brand, S, Sullivan, KE, Orange, JS, Fevang, B, Schreiber, S, Lieb, W, Aukrust, P, Chapel, H, Cunningham-Rundles, C, Franke, A, Karlsen, TH, Grimbacher, B, Hakonarson, H, Hammarström, L & Ellinghaus, E 2015, 'Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells', Nature Communications, Jg. 6, 6804. https://doi.org/10.1038/ncomms7804

TY - JOUR

T1 - Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells

AU - Li, Jin

AU - Jørgensen, Silje F.

AU - Maggadottir, S. Melkorka

AU - Bakay, Marina

AU - Warnatz, Klaus

AU - Glessner, Joseph

AU - Pandey, Rahul

AU - Salzer, Ulrich

AU - Schmidt, Reinhold E.

AU - Perez, Elena

AU - Resnick, Elena

AU - Goldacker, Sigune

AU - Buchta, Mary

AU - Witte, Torsten

AU - Padyukov, Leonid

AU - Videm, Vibeke

AU - Folseraas, Trine

AU - Atschekzei, Faranaz

AU - Elder, James T.

AU - Nair, Rajan P.

AU - Winkelmann, Juliane

AU - Gieger, Christian

AU - Nöthen, Markus M.

AU - Büning, Carsten

AU - Brand, Stephan

AU - Sullivan, Kathleen E.

AU - Orange, Jordan S.

AU - Fevang, Børre

AU - Schreiber, Stefan

AU - Lieb, Wolfgang

AU - Aukrust, Pål

AU - Chapel, Helen

AU - Cunningham-Rundles, Charlotte

AU - Franke, Andre

AU - Karlsen, Tom H.

AU - Grimbacher, Bodo

AU - Hakonarson, Hakon

AU - Hammarström, Lennart

AU - Ellinghaus, Eva

PY - 2015/4/20

Y1 - 2015/4/20

N2 - Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10-9) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10-16). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.

AB - Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10-9) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10-16). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.

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U2 - 10.1038/ncomms7804

DO - 10.1038/ncomms7804

M3 - Article

C2 - 25891430

AN - SCOPUS:84928139974

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6804

ER -

Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells

Abstract

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