IgG (Gm) allotypes and multiple sclerosis in a French population: Phenotype distribution and quantitative abnormalities in CSF with respect to sex, disease severity, and presence of intrathecal antibodies

Sesboüé, Richard; Daveau, Maryvonne; Degos, Jean‐Denis; Martin-Mondiere, C; Goust, Jean‐Michel; Schuller, E; Rivat-Peran, Liliane; Coquerel, Antoine; Dujardin, M.; Salier, Jean‐Philippe

doi:10.1016/0090-1229(85)90145-x

Cited by 20 publications

(2 citation statements)

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“…Although the Gm21* haplotype is not associated with higher IgG serum levels, 35 we cannot exclude that it goes along with a higher IgG synthesis of plasma cells and plasmablasts infiltrating the CNS compartment. 10 Conflicting results have been reported for the correlation of the GM allotype with susceptibility, severity, and course of MS as well as with absolute CSF IgG levels in MS. [35][36][37][38][39][40] SNPs of the IGHC locus have not been analyzed in the latest MS GWASs, 8 because they have not been adequately genotyped in all controls. In the present study, analysis of the identified candidate SNPs in a subset of cases and controls revealed no evidence of association of the IGHC locus with susceptibility to MS.…”

Section: Discussionmentioning

confidence: 99%

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Genetic variants in the immunoglobulin heavy chain locus are associated with the IgG index in multiple sclerosis

Buck

Albrecht

Aslam

et al. 2012

Annals of Neurology

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Objective Intrathecal synthesis of immunoglobulin gamma (IgG) synthesis is frequently observed in patients with multiple sclerosis (MS). Whereas the extent of intrathecal IgG synthesis varies largely between patients, it remains rather constant in the individual patient over time. The aim of this study was to identify common genetic variants associated with the IgG index as a marker of intrathecal IgG synthesis in MS. Methods We performed a genome-wide association study of the IgG index in a discovery series of 229 patients. For confirmation we performed a replication in 2 independent series comprising 256 and 153 patients, respectively. The impact of associated single nucleotide polymorphisms (SNPs) on MS susceptibility was analyzed in an additional 1,854 cases and 5,175 controls. Results Significant association between the IgG index and 5 SNPs was detected in the discovery and confirmed in both replication series reaching combined p values of p = 6.5 × 10−11 to p = 7.5 × 10−16. All identified SNPs are clustered around the immunoglobulin heavy chain (IGHC) locus on chromosome 14q32.33 and are in linkage disequilibrium (r2 range, 0.71–0.95). The best associated SNP is located in an intronic region of the immunoglobulin gamma3 heavy chain gene. Additional sequencing identified the GM21* haplotype to be associated with a high IgG index. Further evaluation of the IGHC SNPs revealed no association with susceptibility to MS in our data set. Interpretation The extent of intrathecal IgG in MS is influenced by the IGHC locus. No association with susceptibility to MS was found. Therefore GM haplotypes might affect intrathecal IgG synthesis independently of the underlying disease

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Section: Discussionmentioning

confidence: 99%

“…Conflicting results have been reported for the correlation of the GM allotype with susceptibility, severity, and course of MS as well as with absolute CSF IgG levels in MS 35–40. SNPs of the IGHC locus have not been analyzed in the latest MS GWASs,8 because they have not been adequately genotyped in all controls.…”

Section: Discussionmentioning

confidence: 99%