Background and objective:
Acute disseminated encephalomyelitis (ADEM) and relapsing–remitting
multiple sclerosis (RRMS) share overlapping clinical,
radiologic and laboratory features at onset.
Because autoantibodies may contribute to the pathogenesis of both
diseases, we
sought to identify autoantibody biomarkers that
are capable of distinguishing them.
Methods: We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with paediatric
ADEM (n = 15), paediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n
= 15). Using isotype-specific secondary antibodies, we profiled both
IgG and IgM reactivities. We used Statistical Analysis
of Microarrays software to confirm the
differences in autoantibody reactivity profiles between ADEM and MS
samples. We used
Prediction Analysis of Microarrays software to
generate and validate prediction algorithms, based on the autoantibody
reactivity
profiles.
Results: ADEM was
characterized by IgG autoantibodies targeting epitopes derived from
myelin basic protein, proteolipid protein, myelin-associated
oligodendrocyte basic glycoprotein, and
alpha-B-crystallin. In contrast, MS was characterized by IgM
autoantibodies targeting
myelin basic protein, proteolipid protein,
myelin-associated oligodendrocyte basic glycoprotein and
oligodendrocyte-specific
protein. We generated and validated prediction
algorithms that distinguish ADEM serum (sensitivity 62–86%; specificity
56–79%)
from MS serum (sensitivity 40–87%; specificity
62–86%) on the basis of combined IgG and IgM anti-myelin autoantibody
reactivity
to a small number of myelin peptides.
Conclusions: Combined
profiles of serum IgG and IgM autoantibodies identified myelin antigens
that may be useful for distinguishing MS
from ADEM. Further studies are required to
establish clinical utility. Further biological assays are required to
delineate
the pathogenic potential of these antibodies.
IgM is usually the first type of antibody produced in an immune response and this often switches to producing IgG. In this study they found that ADEM was associated with the presence of IgG antibodies to certain myelin targets. In MS there was association with certain IgM antibodies against certain myelin proteins and created a prediction assay but it is not really good enough as a predictor as it fails to spot in 10-50% of the time and cannot distinguish what is MS versus ADEM in 25-40% of the time. If you needed this information to start a treatment many people would not get it, or would get the wrong treatment, perhaps. So a good start but we need to do better.