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Updated: Jun 23, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Multiple sclerosis associates with LILRA3 deletion in Spanish patients
D Ordóñez1, A J Sánchez, J E Martínez-Rodríguez
1Inmunogenética - HLA, Hospital Universitario Puerta de Hierro, 28220 Majadahonda, Spain.
Abstract:
The genetic susceptibility to multiple sclerosis (MS) is only partially explained, and it shows geographic variations. We analyse here two series of Spanish patients and healthy controls and show that relapsing MS (R-MS) is associated with a gene deletion affecting the hypothetically soluble leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3, 19q13.4), in agreement with an earlier finding in German patients. Our study points to a gene-dose-dependent, protective role for LILRA3, the deletion of which synergizes with HLA-DRB1(*)1501 to increase the risk of R-MS. We also investigated whether the risk of suffering R-MS might be influenced by the genotypic diversity of killer-cell Ig-like receptors (KIRs), located only approximately 400 kb telomeric to LILRA3, and implicated in autoimmunity and defence against viruses. The relationship of LILRA3 deletion with R-MS is not secondary to linkage disequilibrium with a KIR gene, but we cannot exclude some contributions of KIR to the genetic susceptibility to R-MS.
Insights
A specific gene deletion, leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3), is linked to an increased risk of relapsing multiple sclerosis (R-MS). This deletion interacts with another gene, HLA-DRB1(*)1501, to further elevate R-MS risk.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Human Genetics
Background:
- Genetic susceptibility to multiple sclerosis (MS) is complex and exhibits geographical variations.
- Previous studies suggested a link between MS and genetic factors, but the full picture remains incomplete.
Purpose of the Study:
- To investigate the association between genetic variations and relapsing MS (R-MS) in a Spanish population.
- To explore the role of leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3) deletion and killer-cell Ig-like receptors (KIRs) in R-MS susceptibility.
Main Methods:
- Analysis of two Spanish cohorts of patients with R-MS and healthy controls.
- Genotyping for LILRA3 deletion and investigation of its interaction with HLA-DRB1(*)1501.
- Assessment of the influence of KIR genotypic diversity on R-MS risk.
Main Results:
- A significant association was found between R-MS and the deletion of LILRA3 (19q13.4).
- The LILRA3 deletion demonstrates a gene-dose-dependent protective effect, with its absence increasing R-MS risk.
- LILRA3 deletion synergizes with HLA-DRB1(*)1501 to significantly elevate the risk of R-MS.
- The association of LILRA3 deletion with R-MS is independent of linkage disequilibrium with KIR genes, although KIRs may still contribute to MS susceptibility.
Conclusions:
- LILRA3 deletion is a risk factor for relapsing multiple sclerosis, particularly in conjunction with HLA-DRB1(*)1501.
- The findings support a protective role for LILRA3 in the context of MS.
- Further research is warranted to fully elucidate the contribution of KIR genes to MS genetic susceptibility.
