Contributions
Abstract: EP1427
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Immunology
The identification of antigenic targets of the autoimmune response in multiple sclerosis (MS) is crucial for the understanding of MS pathogenesis. We have previously identified increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in plasma samples from 1,063 MS cases compared with 1,106 controls, where 15.4% of the cases and 3.2% of the controls were positive based on a threshold set at median fluorescent intensity (MFI) plus three standard deviations (3xSD) in controls. An interaction on the additive scale between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele was also detected [1].
In this study, we determined IgG antibody levels directed towards protein fragments including ANO2 using bead-based suspension array technology in a larger independent replication cohort of 7,199 MS cases and 5,742 controls from Sweden. We confirmed that MS patients have statistically significant higher levels of anti-ANO2 [79-167] antibodies compared to controls (Wilcoxon p-value < 2.2 x 10-16). Using a cut-off at median MFI plus 3xSD in controls, 5.3% of MS cases and 1.9% of controls were positive resulting in an odds ratio (OR) for MS of 3.0, 95% confidence interval (CI): 2.4-3.8 (Fisher"s Exact p-value < 2.2 x 10-16). We detected a strong interaction between the presence of ANO2 autoantibodies and the DRB1*15 allele with an attributable proportion (AP) due to interaction of 0.5 (95% CI: 0.3-0.7; p-value = 9.2x10-7). The risk for MS is 11 times higher among individuals that carry both risk factors compared to those with none of these two factors (OR=11.0, 95% CI: 7.2 - 16.7).
In conclusion, we have now confirmed, in a large independent cohort of MS patients and controls, an increased IgG reactivity towards ANO2 in MS. Further, ANO2 reactivity seems to be part of the same sufficient cause for MS as DRB1*15.
1. Ayoglu B, Mitsios N, Kockum I, Khademi M, Zandian A, Sjoberg R, Forsstrom B, Bredenberg J, Lima Bomfim I, Holmgren E et al: Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America 2016, 113(8):2188-2193.
Disclosure:
Katarina Tengvall: nothing to disclose.
Izaura Lima Bomfim: nothing to disclose.
Angelika Michel: nothing to disclose.
Jesse Huang: nothing to disclose.
Burcu Ayoglu: nothing to disclose.
Lars Alfredsson receives research support from the Swedish Medical Research Council (Dnr 521-2012-2917), Swedish Council for Health, Working Life and Welfare (Dnr 2012-0325) and Swedish Brain Foundation.
Peter Nilsson: nothing to disclose.
Tim Waterboer: nothing to disclose.
Tomas Olsson has received lecture and/or advisory board honoraria, and unrestricted MS research grants from Astrazeneca, Biogen, Novartis , Allmiral and Genzyme.
Ingrid Kockum has recieved honoraria for lecture from Merck Serono.
Abstract: EP1427
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Immunology
The identification of antigenic targets of the autoimmune response in multiple sclerosis (MS) is crucial for the understanding of MS pathogenesis. We have previously identified increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in plasma samples from 1,063 MS cases compared with 1,106 controls, where 15.4% of the cases and 3.2% of the controls were positive based on a threshold set at median fluorescent intensity (MFI) plus three standard deviations (3xSD) in controls. An interaction on the additive scale between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele was also detected [1].
In this study, we determined IgG antibody levels directed towards protein fragments including ANO2 using bead-based suspension array technology in a larger independent replication cohort of 7,199 MS cases and 5,742 controls from Sweden. We confirmed that MS patients have statistically significant higher levels of anti-ANO2 [79-167] antibodies compared to controls (Wilcoxon p-value < 2.2 x 10-16). Using a cut-off at median MFI plus 3xSD in controls, 5.3% of MS cases and 1.9% of controls were positive resulting in an odds ratio (OR) for MS of 3.0, 95% confidence interval (CI): 2.4-3.8 (Fisher"s Exact p-value < 2.2 x 10-16). We detected a strong interaction between the presence of ANO2 autoantibodies and the DRB1*15 allele with an attributable proportion (AP) due to interaction of 0.5 (95% CI: 0.3-0.7; p-value = 9.2x10-7). The risk for MS is 11 times higher among individuals that carry both risk factors compared to those with none of these two factors (OR=11.0, 95% CI: 7.2 - 16.7).
In conclusion, we have now confirmed, in a large independent cohort of MS patients and controls, an increased IgG reactivity towards ANO2 in MS. Further, ANO2 reactivity seems to be part of the same sufficient cause for MS as DRB1*15.
1. Ayoglu B, Mitsios N, Kockum I, Khademi M, Zandian A, Sjoberg R, Forsstrom B, Bredenberg J, Lima Bomfim I, Holmgren E et al: Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America 2016, 113(8):2188-2193.
Disclosure:
Katarina Tengvall: nothing to disclose.
Izaura Lima Bomfim: nothing to disclose.
Angelika Michel: nothing to disclose.
Jesse Huang: nothing to disclose.
Burcu Ayoglu: nothing to disclose.
Lars Alfredsson receives research support from the Swedish Medical Research Council (Dnr 521-2012-2917), Swedish Council for Health, Working Life and Welfare (Dnr 2012-0325) and Swedish Brain Foundation.
Peter Nilsson: nothing to disclose.
Tim Waterboer: nothing to disclose.
Tomas Olsson has received lecture and/or advisory board honoraria, and unrestricted MS research grants from Astrazeneca, Biogen, Novartis , Allmiral and Genzyme.
Ingrid Kockum has recieved honoraria for lecture from Merck Serono.