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| Thank you Robert Guthrie @ Wikipedia |
Just in case this makes no sense to you, the basic suggestion is that all those dried blood spots taken from days old infants to test for various inborn errors of metabolism like PKU, could be used to examine the switching on or off of genes well before most diseases or conditions become apparent. At the very least it would compare what's there at birth with what might be there at later stages in life and focus attention on factors in that intervening period.
I'm interested in this area for lots of different reasons. Not least that infant dried blood spots - whilst a little traumatic to see when blood is taken from this tiny little baby - are indeed a treasure trove of information waiting to be discovered. With regards to a condition like autism(s) which only really manifest in early childhood, there could be several markers, endophenotypic biomarkers, waiting on those little pieces of card and possibly not just all epigentic ones.
Indeed I'm very happy to report that autism research has already taken advantage of the infant dried blood spots available as evidenced by this study by Abdallah and colleagues** on neonatal levels of cytokines in cases of autism. Regular readers will know that I've done cytokines and autism on the blog quite a few times (see here for example). Cytokines, those chemical messengers, linked to interesting things like inflammation are finding a real home in autism research and other areas of investigation but still some questions need to be answered (why? who? what to do about it?).
Abdallah et al looked at several hundred neonatal blood spot samples (n=359) where autism was eventually confirmed compared with a sizable control population (n=741). They found quite a bit of evidence to suggest that children with autism were more likely to present with 'hypoactive immune cell activity' as youngsters than controls including lower levels of everyone's favourite interferon, interferon gamma.
I've talked before about the often conflicting results on immune function in cases of autism and how researchers such as Harumi Jyonouchi have presented similarly 'depressed' immune function related to cases of autism whilst others report immune over-activity or the presence of autoantibodies. I will at this point press a few words home to you: heterogeneity, endophenotypes, comorbidity and gene-environment interactions.
Indeed this recent study by Goines and Ashwood*** (Paul Ashwood that is) kinda summarises how complicated cytokine dysregulation seems to be with autism in mind and how environment combined with genetics may very well play an important role in the presentation of immune function in cases of autism.
Neonatal blood spots offer a fascinating opportunity to explore lots and lots of features potentially related to autism and beyond. Neonatal vitamin D status as per this study by McGrath and colleagues**** using the same Danish neonatal database following on from the recent interest in vitamin D and autism is just one example of where this could go. Indeed given the millions of people around the world who undergo neonatal blood spot screening every year, the possibilities of comparisons by diagnosis, geography, ethnicity, etc. and across different times, are seemingly endless.
To finish a song by another Robert (Smith not Guthrie) about it being Friday and someone being in love? (even though at the time of publication of this post, it is actually still Tuesday where I am).
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* Beyan H. et al. Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans. Genome Research. August 2012.
** Abdallah MW. et al. Neonatal levels of cytokines and risk of autism spectrum disorders: An exploratory register-based historic birth cohort study utilizing the Danish Newborn Screening Biobank. Journal of Neuroimmunology. August 2012.
*** Goines PE. & Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment. Neurotoxicology & Teratology. August 2012.
**** McGrath JJ. et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Archives of General Psychiatry. 2010; 67: 889-894.
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Abdallah MW, Larsen N, Mortensen EL, Atladóttir HO, Nørgaard-Pedersen B, Bonefeld-Jørgensen EC, Grove J, & Hougaard DM (2012). Neonatal levels of cytokines and risk of autism spectrum disorders: An exploratory register-based historic birth cohort study utilizing the Danish Newborn Screening Biobank. Journal of neuroimmunology PMID: 22917523
Hi Paul Whiteley -
ReplyDeleteWith regards to a condition like autism(s) which only really manifest in early childhood, there could be several markers, endophenotypic biomarkers, waiting on those little pieces of card and possibly not just all epigentic ones.
Indeed. One of the biggest pieces of information that may be available from this type of stored blood is insight into the incidence question. If we get clever enough to understand chemical or epigenetic profiles that lead to increased risk for one endophenotype or another, we may be able to go back in time to see if there has been a change in the number of infants with that same pattern. It won't answer the question of incidence, but it could give us more empirical evidence, one way or the other.
Nice write up.
- pD
Thanks pD.
ReplyDeleteA very, very good point indeed. According to a number of sources dotted about the web, the newborn screening programme has been consistently running since the late 1960s. Outside of issue such as storage and how time may degrade the cards and samples, there is sound reasoning in assuming that if a biomarker/s could be isolated, we can go back and check the samples.
Many thanks again.