Wednesday, 13 March 2013

Research: genetic risk of oligoclonal bands

#MSBlog: Is OCB-ve MS a different disease? 

Epub: Mero IL et al. Oligoclonal band status in scandinavian multiple sclerosis patients is associated with specific genetic risk alleles. PLoS One. 2013;8(3):e58352. doi: 10.1371/journal.pone.0058352. 

Background: The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in MS. 

Methods: The investigators' pplied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MSers from a genome-wide association study (GWAS) to search for genetic differences in MS relating to OCB status. GWAS data was compared in 1367 OCB positive and 161 OCB negative Scandinavian MSers, and nine of the most associated SNPs were genotyped for replication in 3403 Scandinavian MSers. Genotypes were analyzed in a subset of the OCB positive (n = 2781) and OCB negative (n = 292) MSers and compared to 890 healthy controls. 

Results: Results from the genome-wide analyses showed that single nucleotide polymorphisms (SNPs) from the HLA complex and six other loci were associated to OCB status. In SNPs selected for replication, combined analyses showed genome-wide significant association for two SNPs in the HLA complex; rs3129871 (p = 5.7×10) and rs3817963 (p = 5.7×10) correlating with the HLA-DRB1*15 and the HLA-DRB1*04 alleles, respectively. They also found suggestive association to one SNP in the gene (p = 8.83×10). In analyses HLA-DRB1*15∶01 was a stronger risk factor for OCB positive than OCB negative MS, whereas HLA-DRB1*04∶04 was associated with increased risk of OCB negative MS and reduced risk of OCB positive MS. Protective effects of HLA-DRB1*01∶01 and HLA-DRB1*07∶01 were detected in both groups. The groups were different with regard to age at onset (AAO), MS outcome measures and gender. 

Conclusion: This study confirms both shared and distinct genetic risk for MS subtypes in the Scandinavian population defined by OCB status and indicates different clinical characteristics between the groups. This suggests differences in disease mechanisms between OCB negative and OCB positive MS with implications for MSers management, which need to be further studied.

OCB patterns: S=serum, L=liquor or CSF. Patterns with bands in the CSF that are not present in the serum is what occurs in MSers. The sensitivity of this test depends on the technique used. This picture is using the state of the art technique (IEF with immunofixation); using this technique ~98% of MSers are OCB+ve.

"The elephant in the room in this study is the question of whether or not OCB-ve MS, is MS? I have always hypothesised that when we find the cause of MS we will find that the majority of MSers who are OCB-ve will turn-out to have a different disease. This study confirms my suspicion that the OCB-ve population is different to the OCB+ve population. I am also not surprised by this studies findings; variations in the gene that are strongly associated with susceptibility to MS differ between OCB-ve and OCB+ve MS; this is what you would expect if these populations represent different diseases. Do you find these results interesting?"

3 comments:

  1. This is interesting.

    And my question would be if these findings correlate with progressive and relapsing form of MS.

    E.g. progresseive more likly to have OCB-ve, relapsing more likle to have OCB+ve

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    1. As far as I know OCB-ve people have better diagnosis while OCB+ve people (the vast majority) a worse one. Would make sense to say that the minority is maybe a different disease altogether. Still the mystery remains why the bands are in our lumbal fluid in the first place....

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  2. Re. prognosis - although the evidence would suggest that OCB positive people may have a worse prognosis, there is a clear publication bias in the data. When I looked at this recently, pretty much all of the studies reporting no effect on prognosis of OCBs gave those results in a single line with no numbers (i.e. not as the main focus), whereas those with positive findings devoted a lot more space to the results.
    however, if you have CIS then the presence of OCBs does confer a much higher risk of conversion.
    i think the paper looking at this is discussed on here somewhere... http://multiple-sclerosis-research.blogspot.co.uk/2013/03/research-oligoclonal-bands-in-cis.html (CoI it's my work!)

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