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. 2009 Aug 18;213(1-2):123-30.
doi: 10.1016/j.jneuroim.2009.05.014. Epub 2009 Jul 24.

Potential of a Unique Antibody Gene Signature to Predict Conversion to Clinically Definite Multiple Sclerosis

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Free PMC article

Potential of a Unique Antibody Gene Signature to Predict Conversion to Clinically Definite Multiple Sclerosis

Elizabeth M Cameron et al. J Neuroimmunol. .
Free PMC article

Abstract

We identified a unique antibody gene mutation pattern (i.e. "signature") in cerebrospinal fluid (CSF) B cells from multiple sclerosis (MS) patients not present in control populations. Prevalence of the signature in CSF B cells of patients at risk to develop MS predicted conversion to MS with 91% accuracy in a small cohort of clinically isolated syndrome patients. If confirmed, signature prevalence would be a novel genetic diagnostic tool candidate for patients with early demyelinating disease of the central nervous system.

Figures

Figure 1
Figure 1. Example of VH4 comparison
A VH4–30.4 sequence is listed as the germline configuration (allele 01) and compared to a patient CD19+ B cell sequence. The germline protein conversion and the changes made by replacement mutations in the patient sequence are noted. Signature codons are boxed, with the dashed boxes demarcating cold spots, and the solid boxes demarcating hot spots. CDRs as defined by Kabat (Kabat et al., 1983) are shaded.
Figure 2
Figure 2. Signature score in individual MS and CIS patients
Signature scores were generated by calculating Z-scores for the RF values at the 6 codons within the signature (31B, 40, 56, 57, 81 and 89). Individual z-scores at each of the codon positions were compiled to generate the composite signature z-score. MS patient signature scores are shown as black circles (●), CIS patient signature scores that resulted in prediction of CDMS are black squares (■), and CIS patient signature scores that resulted in prediction of unlikely to convert to definite MS are in open squares (□). The average composite signature score in the MSCSFVH4 database was 10.9 ±2.0 (black line) and so any signature score of an individual CIS patient above 6.8 (average – 2 S.D.; threshold shown as red line) was predicted to convert to CDMS. For reference, ONDCSFVH4 group signature score was 4.5, and MSPBVH4 signature score was 2.0.

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