好色先生

好色先生

Explore the latest content from across our publications
Join The AAN

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Genetic Insights from Whole Exome Sequencing on IL-6 Signaling Genes in NMOSD: Unraveling Potential Mechanisms of Inflammation and Treatment Outcomes Driven by Anti-AQP4 Status and Ethnical backgrounds
Autoimmune Neurology
S38 - NMOSD, MOGAD, Demyelinating, and Other (2:36 PM-2:48 PM)
009

To identify potential genetic modulators of IL-6 signaling within a serodiverse anti-AQP4 NMOSD cohort and examine the distribution of significant genetic variants across different ethnic backgrounds and their predicted effects on gene expression.
IL-6 signaling is a key pathway in the pathophysiology of NMOSD. Genetic factors influencing IL-6-related genes may explain variations in disease mechanisms and treatment responses among anti-AQP4 serogroups. Additionally, ethnic background appears to influence disease susceptibility. However, no studies have explored these aspects in this rare autoimmune disease.

Genetic variants from whole-exome sequencing of 29 anti-AQP4 (+) and 11 anti-AQP4 (-) NMOSD patients were screened within IL-6 signaling genes across both serogroups. Population databases were utilized for variant frequency analysis. In silico predictions of gene expression effects were performed using eQTL databases and relevant literature.
The variant rs2228044 in IL6ST is associated with the seropositive group and linked to lower sgp130 levels, suggesting a potential role in disease mechanisms that warrants further investigation. Variants rs3810194 and rs2878342 in FCGRT are predicted to reduce gene expression, potentially impacting the recycling rate of the anti-IL6 monoclonal antibody, Satralizumab. According to the dbSNP database, all three variants are more frequently found in populations of African ancestry.
The variant rs2228044 in IL6ST has been associated with lower sgp130 levels, an inhibitor of IL-6 trans-signaling, potentially contributing to a heightened basal inflammatory state in the anti-AQP4 seropositive group. This role in inflammation warrants further study to understand its impact on disease progression. Additionally, variants rs3810194 and rs2878342 in FCGRT may reduce its gene expression, affecting the recycling rate and efficacy of Satralizumab in the seronegative group. Notably, these variants are more frequent in individuals of African ancestry. Further investigation is needed into the clinical implications of these variants on NMOSD pathophysiology and treatment outcomes.
Authors/Disclosures
Elisa G. Gouvea
PRESENTER 		Miss Gouvea has nothing to disclose.
Elielson Veloso da Silva, PhD Dr. Veloso da Silva has nothing to disclose.
Renan A. Fernandes (Universidade Federal do Estado do Rio de Janeiro) Ms. Fernandes has nothing to disclose.
Jéssica Vedovi Jéssica Vedovi has nothing to disclose.
Larissa Duarte (UFRJ) Miss Duarte has nothing to disclose.
Andreza S. Lemos, PhD (UNIRIO - University of State of Rio de Janeiro) Dr. Lemos has nothing to disclose.
Helena França F. Ferreira, Master Mr. Ferreira has nothing to disclose.
Anna Beatriz S. Vanzan, Student Miss Vanzan has nothing to disclose.
Karla P. Fadel Miss Fadel has nothing to disclose.
Valéria Coelho Santa Rita Pereira (Clementino Fraga Filho University Hospital, UFRJ, Brazil.) No disclosure on file
Soniza Vieira A. Leon, Sr., MD, PhD (Universidade Federal do Rio de Janeiro) Dr. Leon has nothing to disclose.