G Model MIMM-4463; No. of Pages 1
ARTICLE IN PRESS Molecular Immunology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Molecular Immunology journal homepage: www.elsevier.com/locate/molimm
Letter to the Editor MBL, a potential therapeutic target for type 1 diabetes?
Conflict of interest statement The authors have no potential conflicts of interest.
To the editor, We read with interest the article “Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings” published in Molecular Immunology identifying that more type 1 diabetes (T1D) patients had mannose binding lectin (MBL) levels above 0.8 g/ml than their healthy siblings, and elevated MBL levels were related to high producing MBL genotypes, correlated with high levels of inflammatory cytokines, including TNF-␣, IL-1, IL-12, IL-18 (Sildorf et al., 2014). During the study period (1997–2005), MBL levels were increased in T1D patients, and siblings showed seasonal variance in concentrations with the lowest level in wintertime (Sildorf et al., 2014). These findings indicated that MBL may be a potential therapeutic target in T1D. MBL is a key mediator in innate immunity. MBL insufficiency associated with increased susceptibility to infections and some autoimmune diseases. Mice treated with streptozotocin have been reported to result in diabetes, by which diabetes induction can lead to increased MBL-C concentration. The increase in MBL-C expression correlated with elevated glucose levels (Ostergaard et al., 2013). Bouwman et al. (2005) found higher MBL levels and MBL complex activity in newly diagnosed T1D patients compared with their siblings matched for high producing MBL genotypes. In a study for 5.8 ± 2.2 years’ follow-up, Hansen et al. (2010) put forward an idea that baseline MBL was increased in T1D patients, about 20% of the T1D patients progressed to a higher albuminuria level or end-stage renal disease. MBL levels were higher in progressors compared with non-progressors at all steps of progression (Hansen et al., 2010). In addition, frequency of the minor allele of codon 54 was 24.2% in the Japanese T1D patients and 19.9% in the controls, and the probability of being heterozygous or homozygous for the minor allele was 41.4% in the patients and 33.3% in the controls, suggesting that possession of the minor allele of the Mbl gene may be a minor risk factor for T1D (Tsutsumi et al., 2003). However, the allele frequency of single nucleotide polymorphisms located in exon 1 and the promoter region of the Mbl2 gene was comparable between patients and healthy controls in the Netherlands (Bouwman et al., 2005). Similarly, there was no significant effect of MBL2 genotypes on the risk or onset age of T1D in Finnish population (Aittoniemi et al., 2008). Collectively, available evidence suggests a valuable role that MBL may play in T1D. However, further studies are still needed to comprehensively explore the role of MBL in T1D. Therefore, therapeutic agent targeting may lead to innovative new therapies for T1D.
Acknowledgement This work was partly supported by grants from the health, family planning projects of Shanghai Pudong (PW2014A-1), training plan for academic leader of health system of Shanghai Pudong (PWRd2012-03). References Aittoniemi, J., Turpeinen, H., Tiittanen, M., Knip, M., Simell, O., Ilonen, J., Vaarala, O., 2008. Relation among mannose-binding lectin 2 genotype, beta-cell autoantibodies, and risk for type 1 diabetes in Finnish children. Hum. Immunol. 69, 108–111. Bouwman, L.H., Eerligh, P., Terpstra, O.T., Daha, M.R., de Knijff, P., Ballieux, B.E., Bruining, G.J., van der Slik, A.R., Roos, A., Roep, B.O., 2005. Elevated levels of mannose-binding lectin at clinical manifestation of type 1 diabetes in juveniles. Diabetes 54, 3002–3006. Hansen, T.K., Forsblom, C., Saraheimo, M., Thorn, L., Wadén, J., Høyem, P., Østergaard, J., Flyvbjerg, A., Groop, P.H., 2010. Association between mannose-binding lectin, high-sensitivity C-reactive protein and the progression of diabetic nephropathy in type 1 diabetes. Diabetologia 53, 1517–1524. Ostergaard, J.A., Bjerre, M., Dagnaes-Hansen, F., Hansen, T.K., Thiel, S., Flyvbjerg, A., 2013. Diabetes-induced changes in mannan-binding lectin levels and complement activation in a mouse model of type 1 diabetes. Scand. J. Immunol. 77, 187–194. Sildorf, S.M., Eising, S., Hougaard, D.M., Mortensen, H.B., Skogstrand, K., Pociot, F., Johannesen, J., Svensson, J., 2014. Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings. Mol. Immunol. 62, 71–76. Tsutsumi, A., Ikegami, H., Takahashi, R., Murata, H., Goto, D., Matsumoto, I., Fujisawa, T., Sumida, T., 2003. Mannose binding lectin gene polymorphism in patients with type I diabetes. Hum. Immunol. 64, 621–624.
Shan-Shan Liu Ji-Quan Lou Ye Ding ∗ Department of Health Evaluation, Shanghai Pudong Institute for Health Development, Pudong, Shanghai, PR China ∗ Corresponding author at: Shanghai Pudong Institute for Health Development, 818 Laiyang Road, Pudong, Shanghai, PR China. Tel.: +86 21 60880508; fax: +86 21 60753213. E-mail address: [email protected] (Y. Ding)
29 June 2014 Available online xxx
http://dx.doi.org/10.1016/j.molimm.2014.07.022 0161-5890/Crown Copyright © 2014 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Liu, S.-S., et al., MBL, a potential therapeutic target for type 1 diabetes? Mol. Immunol. (2014), http://dx.doi.org/10.1016/j.molimm.2014.07.022
ARTICLE IN PRESS Molecular Immunology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Molecular Immunology journal homepage: www.elsevier.com/locate/molimm
Letter to the Editor MBL, a potential therapeutic target for type 1 diabetes?
Conflict of interest statement The authors have no potential conflicts of interest.
To the editor, We read with interest the article “Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings” published in Molecular Immunology identifying that more type 1 diabetes (T1D) patients had mannose binding lectin (MBL) levels above 0.8 g/ml than their healthy siblings, and elevated MBL levels were related to high producing MBL genotypes, correlated with high levels of inflammatory cytokines, including TNF-␣, IL-1, IL-12, IL-18 (Sildorf et al., 2014). During the study period (1997–2005), MBL levels were increased in T1D patients, and siblings showed seasonal variance in concentrations with the lowest level in wintertime (Sildorf et al., 2014). These findings indicated that MBL may be a potential therapeutic target in T1D. MBL is a key mediator in innate immunity. MBL insufficiency associated with increased susceptibility to infections and some autoimmune diseases. Mice treated with streptozotocin have been reported to result in diabetes, by which diabetes induction can lead to increased MBL-C concentration. The increase in MBL-C expression correlated with elevated glucose levels (Ostergaard et al., 2013). Bouwman et al. (2005) found higher MBL levels and MBL complex activity in newly diagnosed T1D patients compared with their siblings matched for high producing MBL genotypes. In a study for 5.8 ± 2.2 years’ follow-up, Hansen et al. (2010) put forward an idea that baseline MBL was increased in T1D patients, about 20% of the T1D patients progressed to a higher albuminuria level or end-stage renal disease. MBL levels were higher in progressors compared with non-progressors at all steps of progression (Hansen et al., 2010). In addition, frequency of the minor allele of codon 54 was 24.2% in the Japanese T1D patients and 19.9% in the controls, and the probability of being heterozygous or homozygous for the minor allele was 41.4% in the patients and 33.3% in the controls, suggesting that possession of the minor allele of the Mbl gene may be a minor risk factor for T1D (Tsutsumi et al., 2003). However, the allele frequency of single nucleotide polymorphisms located in exon 1 and the promoter region of the Mbl2 gene was comparable between patients and healthy controls in the Netherlands (Bouwman et al., 2005). Similarly, there was no significant effect of MBL2 genotypes on the risk or onset age of T1D in Finnish population (Aittoniemi et al., 2008). Collectively, available evidence suggests a valuable role that MBL may play in T1D. However, further studies are still needed to comprehensively explore the role of MBL in T1D. Therefore, therapeutic agent targeting may lead to innovative new therapies for T1D.
Acknowledgement This work was partly supported by grants from the health, family planning projects of Shanghai Pudong (PW2014A-1), training plan for academic leader of health system of Shanghai Pudong (PWRd2012-03). References Aittoniemi, J., Turpeinen, H., Tiittanen, M., Knip, M., Simell, O., Ilonen, J., Vaarala, O., 2008. Relation among mannose-binding lectin 2 genotype, beta-cell autoantibodies, and risk for type 1 diabetes in Finnish children. Hum. Immunol. 69, 108–111. Bouwman, L.H., Eerligh, P., Terpstra, O.T., Daha, M.R., de Knijff, P., Ballieux, B.E., Bruining, G.J., van der Slik, A.R., Roos, A., Roep, B.O., 2005. Elevated levels of mannose-binding lectin at clinical manifestation of type 1 diabetes in juveniles. Diabetes 54, 3002–3006. Hansen, T.K., Forsblom, C., Saraheimo, M., Thorn, L., Wadén, J., Høyem, P., Østergaard, J., Flyvbjerg, A., Groop, P.H., 2010. Association between mannose-binding lectin, high-sensitivity C-reactive protein and the progression of diabetic nephropathy in type 1 diabetes. Diabetologia 53, 1517–1524. Ostergaard, J.A., Bjerre, M., Dagnaes-Hansen, F., Hansen, T.K., Thiel, S., Flyvbjerg, A., 2013. Diabetes-induced changes in mannan-binding lectin levels and complement activation in a mouse model of type 1 diabetes. Scand. J. Immunol. 77, 187–194. Sildorf, S.M., Eising, S., Hougaard, D.M., Mortensen, H.B., Skogstrand, K., Pociot, F., Johannesen, J., Svensson, J., 2014. Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings. Mol. Immunol. 62, 71–76. Tsutsumi, A., Ikegami, H., Takahashi, R., Murata, H., Goto, D., Matsumoto, I., Fujisawa, T., Sumida, T., 2003. Mannose binding lectin gene polymorphism in patients with type I diabetes. Hum. Immunol. 64, 621–624.
Shan-Shan Liu Ji-Quan Lou Ye Ding ∗ Department of Health Evaluation, Shanghai Pudong Institute for Health Development, Pudong, Shanghai, PR China ∗ Corresponding author at: Shanghai Pudong Institute for Health Development, 818 Laiyang Road, Pudong, Shanghai, PR China. Tel.: +86 21 60880508; fax: +86 21 60753213. E-mail address: [email protected] (Y. Ding)
29 June 2014 Available online xxx
http://dx.doi.org/10.1016/j.molimm.2014.07.022 0161-5890/Crown Copyright © 2014 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Liu, S.-S., et al., MBL, a potential therapeutic target for type 1 diabetes? Mol. Immunol. (2014), http://dx.doi.org/10.1016/j.molimm.2014.07.022
