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Investigating Serum sHLA-G Cooperation With MRI Activity and Disease-Modifying Treatment Outcome in
Roberta Amoriello1, Roberta Rizzo2, Alice Mariottini3
1Department of Clinical and Experimental Medicine (DMSC), University of Florence, Florence, Italy.
Abstract:
Relapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease in which pathogenesis T cells have a major role. Despite the unknown etiology, several risk factors have been described, including a strong association with human leukocyte antigen (HLA) genes. Recent findings showed that HLA class I-G (HLA-G) may be tolerogenic in MS, but further insights are required. To deepen the HLA-G role in MS inflammation, we measured soluble HLA-G (sHLA-G) and cytokines serum level in 27 patients with RRMS at baseline and after 12 and 24 months of natalizumab (NTZ) treatment. Patients were divided into high (sHLA-G>20 ng/ml), medium (sHLA-G between 10 and 20 ng/ml), and low (sHLA-G <10 ng/ml) producers. Results showed a heterogeneous distribution of genotypes among producers, with no significant differences between groups. A significant decrease of sHLA-G was found after 24 months of NTZ in low producers carrying the +3142 C/G genotype. Finally, 83.3% of high and 100% of medium producers were MRI-activity free after 24 months of treatment, compared to 63.5% of low producers. Of note, we did not find any correlation of sHLA-G with peripheral cell counts or cytokines level. These findings suggest that serum sHLA-G level may partly depend on genotype rather than peripheral inflammation, and that may have impacted on MRI activity of patients over treatment.
Insights
Soluble human leukocyte antigen-G (sHLA-G) levels in relapsing-remitting multiple sclerosis (RRMS) patients may be linked to genetic factors, not peripheral inflammation. Lower sHLA-G producers showed reduced treatment response, suggesting a role in disease activity.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Multiple Sclerosis Pathogenesis
Background:
- Relapsing-remitting multiple sclerosis (RRMS) is a T-cell mediated demyelinating disease.
- Human Leukocyte Antigen (HLA) genes are significant risk factors for MS.
- The tolerogenic role of HLA class I-G (HLA-G) in MS requires further investigation.
Purpose of the Study:
- To investigate the role of soluble HLA-G (sHLA-G) and its relationship with disease activity in RRMS.
- To assess changes in sHLA-G and cytokine levels during natalizumab (NTZ) treatment.
- To explore the association between sHLA-G production levels, genotypes, and treatment outcomes.
Main Methods:
- Serum levels of sHLA-G and cytokines were measured in 27 RRMS patients.
- Patients were assessed at baseline and at 12 and 24 months of natalizumab (NTZ) treatment.
- Patients were categorized into high, medium, and low sHLA-G producers based on serum levels.
Main Results:
- A significant decrease in sHLA-G was observed after 24 months of NTZ treatment in low producers with the +3142 C/G genotype.
- High and medium sHLA-G producers showed higher rates of MRI-activity free status after 24 months compared to low producers.
- No correlation was found between sHLA-G levels and peripheral cell counts or cytokine levels.
Conclusions:
- Serum sHLA-G levels in RRMS patients may be influenced by genetic factors rather than peripheral inflammation.
- sHLA-G production levels might impact the effectiveness of natalizumab treatment on MRI-detected disease activity.
- Further research is warranted to elucidate the precise role of HLA-G in MS immunopathogenesis and treatment response.
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