Contributions
Abstract: EP1423
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Correlation patterns of IL-18/anti-IL-18 autoantibodies (auto-Abs) system differed in healthy donors (HD) and multiple sclerosis (MS) patients. The biological role of these auto-Abs is not clear.
The aim of the present study was to investigate whether repertoires of anti-IL-18 auto-Abs differ in MS patients and HDs.
Methods: Blood samples from 51 patients with MS diagnosis have been examined. In addition, blood samples were also obtained from a control group of HD (n=28). The gene sequences were analyzed using SeqMan Lasergene, Vector NTI Suite 8, and MEGA v. 5 software.
We have compared segment composition of the anti-IL-18 single-chain variable fragments (scFvs) selected from MS and naïve phage display libraries.
Results: Considerable differences between anti-IL-18 autoAbs of these libraries were found. VH domains encoded by gene segments belonging to VH3 and VH5 families were present both in MS and naïve panels of anti-IL-18 scFvs. While VH6 domains were present only in the MS panel, VH1 domains were only found in the naïve panel. Heavy chain complementary-determining region 3 (CDR3H) loops of anti-IL-18 auto-Abs from both MS panel were encoded by D segments belonging to D1, D4, D5, and the JH-proximal D7 families.
Conclusion: MS panel contained autoAbs displaying both signs of “fetal” and somatically hypermutated repertoires. Naïve panel mainly contained the naïve antibodies. These variations from the norm are possible results of abnormal regulation of the repertoire perhaps determined by remodeling of the molecular mechanisms involved in the V(D)J recombination and/or abnormal selection by antigen in MS pathogenesis
Disclosure:
D.S. Korobko: nothing to disclose,
M.A. Tyumentseva: nothing to disclose,
N.A. Malkova: nothing to disclose,
M.L. Filipenko: nothing to disclose,
N.V. Tikunova: nothing to disclose
Abstract: EP1423
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Correlation patterns of IL-18/anti-IL-18 autoantibodies (auto-Abs) system differed in healthy donors (HD) and multiple sclerosis (MS) patients. The biological role of these auto-Abs is not clear.
The aim of the present study was to investigate whether repertoires of anti-IL-18 auto-Abs differ in MS patients and HDs.
Methods: Blood samples from 51 patients with MS diagnosis have been examined. In addition, blood samples were also obtained from a control group of HD (n=28). The gene sequences were analyzed using SeqMan Lasergene, Vector NTI Suite 8, and MEGA v. 5 software.
We have compared segment composition of the anti-IL-18 single-chain variable fragments (scFvs) selected from MS and naïve phage display libraries.
Results: Considerable differences between anti-IL-18 autoAbs of these libraries were found. VH domains encoded by gene segments belonging to VH3 and VH5 families were present both in MS and naïve panels of anti-IL-18 scFvs. While VH6 domains were present only in the MS panel, VH1 domains were only found in the naïve panel. Heavy chain complementary-determining region 3 (CDR3H) loops of anti-IL-18 auto-Abs from both MS panel were encoded by D segments belonging to D1, D4, D5, and the JH-proximal D7 families.
Conclusion: MS panel contained autoAbs displaying both signs of “fetal” and somatically hypermutated repertoires. Naïve panel mainly contained the naïve antibodies. These variations from the norm are possible results of abnormal regulation of the repertoire perhaps determined by remodeling of the molecular mechanisms involved in the V(D)J recombination and/or abnormal selection by antigen in MS pathogenesis
Disclosure:
D.S. Korobko: nothing to disclose,
M.A. Tyumentseva: nothing to disclose,
N.A. Malkova: nothing to disclose,
M.L. Filipenko: nothing to disclose,
N.V. Tikunova: nothing to disclose