Loss of immune tolerance to IL-2 in type 1 diabetes

Louis Pérol; John M. Lindner; Pamela Caudana; Nicolas Gonzalo Nunez; Audrey Baeyens; Andrea Valle; Christine Sedlik; Delphine Loirat; Olivier Boyer; Alain Créange; José Laurent Cohen; Ute Christine Rogner; Jun Yamanouchi; Martine Marchant; Xavier Charles Leber; Meike Scharenberg; Marie Claude Gagnerault; Roberto Mallone; Manuela Battaglia; Pere Santamaria; Agnès Hartemann; Elisabetta Traggiai; Eliane Piaggio

doi:10.1038/ncomms13027

Loss of immune tolerance to IL-2 in type 1 diabetes

Louis Pérol, John M. Lindner, Pamela Caudana, Nicolas Gonzalo Nunez, Audrey Baeyens, Andrea Valle, Christine Sedlik, Delphine Loirat, Olivier Boyer, Alain Créange, José Laurent Cohen, Ute Christine Rogner, Jun Yamanouchi, Martine Marchant, Xavier Charles Leber, Meike Scharenberg, Marie Claude Gagnerault, Roberto Mallone, Manuela Battaglia, Pere SantamariaAgnès Hartemann, Elisabetta Traggiai, Eliane Piaggio

IRCCS Ospedale San Raffaele

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

Abstract

Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.

Original language	English
Article number	13027
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13027
Publication status	Published - Oct 6 2016

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms13027

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Pérol, L., Lindner, J. M., Caudana, P., Nunez, N. G., Baeyens, A., Valle, A., Sedlik, C., Loirat, D., Boyer, O., Créange, A., Cohen, J. L., Rogner, U. C., Yamanouchi, J., Marchant, M., Leber, X. C., Scharenberg, M., Gagnerault, M. C., Mallone, R., Battaglia, M., ... Piaggio, E. (2016). Loss of immune tolerance to IL-2 in type 1 diabetes. Nature Communications, 7, [13027]. https://doi.org/10.1038/ncomms13027

Loss of immune tolerance to IL-2 in type 1 diabetes. / Pérol, Louis; Lindner, John M.; Caudana, Pamela; Nunez, Nicolas Gonzalo; Baeyens, Audrey; Valle, Andrea; Sedlik, Christine; Loirat, Delphine; Boyer, Olivier; Créange, Alain; Cohen, José Laurent; Rogner, Ute Christine; Yamanouchi, Jun; Marchant, Martine; Leber, Xavier Charles; Scharenberg, Meike; Gagnerault, Marie Claude; Mallone, Roberto; Battaglia, Manuela; Santamaria, Pere; Hartemann, Agnès; Traggiai, Elisabetta; Piaggio, Eliane.

In: Nature Communications, Vol. 7, 13027, 06.10.2016.

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

Pérol, L, Lindner, JM, Caudana, P, Nunez, NG, Baeyens, A, Valle, A, Sedlik, C, Loirat, D, Boyer, O, Créange, A, Cohen, JL, Rogner, UC, Yamanouchi, J, Marchant, M, Leber, XC, Scharenberg, M, Gagnerault, MC, Mallone, R, Battaglia, M, Santamaria, P, Hartemann, A, Traggiai, E & Piaggio, E 2016, 'Loss of immune tolerance to IL-2 in type 1 diabetes', Nature Communications, vol. 7, 13027. https://doi.org/10.1038/ncomms13027

Pérol, Louis ; Lindner, John M. ; Caudana, Pamela ; Nunez, Nicolas Gonzalo ; Baeyens, Audrey ; Valle, Andrea ; Sedlik, Christine ; Loirat, Delphine ; Boyer, Olivier ; Créange, Alain ; Cohen, José Laurent ; Rogner, Ute Christine ; Yamanouchi, Jun ; Marchant, Martine ; Leber, Xavier Charles ; Scharenberg, Meike ; Gagnerault, Marie Claude ; Mallone, Roberto ; Battaglia, Manuela ; Santamaria, Pere ; Hartemann, Agnès ; Traggiai, Elisabetta ; Piaggio, Eliane. / Loss of immune tolerance to IL-2 in type 1 diabetes. In: Nature Communications. 2016 ; Vol. 7.

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abstract = "Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.",

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N2 - Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.

AB - Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.

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Loss of immune tolerance to IL-2 in type 1 diabetes

Abstract

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