My bafflement continued upon reading the papers by Emilsson and colleagues [1] and by Olivares and colleagues [2]. Respectively suggesting that: "spouses of individuals with celiac disease are at increased risk of non-celiac autoimmune disease" and "a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk" I admit that I had to do a double-take on both these papers.
Accepting that this post is published at the weekend and readers don't necessarily want to listen to me droning on and on, a few quick pointers about each study...
- Emilsson et al including the name of Jonas Ludvigsson (he of the not-quote-coeliac-disease-but-something-in-cases-of-autism (see here)) looked to assess "the risk of non-celiac autoimmune disease [in] first-degree relatives and spouses of people with celiac disease."
- They did this by "searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden" to identify those with coeliac disease (CD) and further through "Swedish healthcare registries" identify first-degree relatives and spouses of those with CD. Hazard ratios (HRs) were calculated "for non-celiac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in relatives/spouses compared with controls."
- Results: over a median follow-up period of about 10 years, some 4% of first-degree relatives of those with CD were diagnosed with an autoimmune condition not CD. This compared with 3% of controls. When it came to calculating those HRs, this translated as a slightly increased likelihood of relatives being diagnosed with an autoimmune condition. Results also suggested something of a similar statistic for spouses (I assume an unrelated individual as a partner).
- Conclusion: "First-degree relatives and spouses of individuals with celiac disease are at increased risk of non-celiac autoimmune disease."
Then to the Olivares paper:
- Drawing on an increasing interest in how those trillions of wee beasties which inhabit our inner depths (the gut microbiota) might do so much more than help us digest our food, researchers set out to look at "whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD." HLA genotype by the way is all about the genetics of identification and communication and how the body distinguishes between 'self' and 'foreign' from an immune perspective (see here). HLA-DQ2 is a bit of a biggie when it comes to risk of CD.
- The gut bacterial composition of infants (exclusively breastfed) either at high or low risk of developing CD by virtue of their genotype (HLA-DQ2 carriers vs. non-HLA-DQ2/8 carriers) were analysed.
- "Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants" among other things.
- Conclusion: "The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition."
There are some pretty obvious issues potentially associated with these papers. Olivares and colleagues in particular, relied on a very small sample size and as far as I can see, were talking about high risk over and above actual diagnosis of CD yet. It will be interesting to see how this pans out. I might also add that whilst gut bacterial composition is a rising star in CD research circles, it would be a brave person/research team who suggested that we have a gut bacterial 'phenotype' of CD (see here). We don't (yet).
The Emilsson findings are just down-right confusing. How can a diagnosis of CD - an autoimmune condition - translate into an increased risk of an autoimmune condition outside of CD for an unrelated spouse? It could be a chance finding; some else to add to the strange collection of results which seem to be emerging [3]. It could be that spouses were by chance also more likely to harbour some of the genetics of autoimmune related conditions as per the cross-over between genotype for CD and something like type 1 diabetes [4]. Now, there's a psychology / sociology experiment waiting to happen. Or it could be due to other factors [5]?
I wonder however whether there may be other explanations for this finding. Short of suggesting that autoimmune conditions might be 'transmissible' I hark back to the peculiar findings reported by Kalliokoski and colleagues [6] and the idea of passive transference of CD "by serum or immunoglobulins" in mice. Granted this was work done with mice and said mice were athymic. But it does present a tantalising suggestion that we might not know as much about autoimmunity as we perhaps thought and even less when it comes to other factors potentially indicated by the results from Moon and colleagues [7] also described in accompanying media (see here) (I'm gonna be blogging about the Moon findings soon too). Think back also to my previous musings on how alcohol and head injury might also tie into sensitisation to gluten and CD respectively.
I continue to be baffled...
And while I remain baffled here is Teenage Fanclub with Star Sign.
The Emilsson findings are just down-right confusing. How can a diagnosis of CD - an autoimmune condition - translate into an increased risk of an autoimmune condition outside of CD for an unrelated spouse? It could be a chance finding; some else to add to the strange collection of results which seem to be emerging [3]. It could be that spouses were by chance also more likely to harbour some of the genetics of autoimmune related conditions as per the cross-over between genotype for CD and something like type 1 diabetes [4]. Now, there's a psychology / sociology experiment waiting to happen. Or it could be due to other factors [5]?
I wonder however whether there may be other explanations for this finding. Short of suggesting that autoimmune conditions might be 'transmissible' I hark back to the peculiar findings reported by Kalliokoski and colleagues [6] and the idea of passive transference of CD "by serum or immunoglobulins" in mice. Granted this was work done with mice and said mice were athymic. But it does present a tantalising suggestion that we might not know as much about autoimmunity as we perhaps thought and even less when it comes to other factors potentially indicated by the results from Moon and colleagues [7] also described in accompanying media (see here) (I'm gonna be blogging about the Moon findings soon too). Think back also to my previous musings on how alcohol and head injury might also tie into sensitisation to gluten and CD respectively.
I continue to be baffled...
And while I remain baffled here is Teenage Fanclub with Star Sign.
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[1] Emilsson L. et al. Autoimmune Disease in First-degree Relatives and Spouses of Individuals with Celiac Disease. Clin Gastroenterol Hepatol. 2015 Jan 30. pii: S1542-3565(15)00112-3.
[2] Olivares M. et al. The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. Gut 2015; 64: 406-417.
[3] Namatovu F. et al. Neighborhood conditions and celiac disease risk among children in Sweden. Scand J Public Health. 2014 Nov;42(7):572-80.
[4] Bao F. et al. One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies. J Autoimmun. 1999 Aug;13(1):143-8.
[5] Skaaby T. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. 2015 Feb 11.
[6] Kalliokoski S. et al. Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease. J Mol Med (Berl). 2015 Jan;93(1):51-62.
[7] Moon C. et al. Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature. 2015. Feb 16.
[3] Namatovu F. et al. Neighborhood conditions and celiac disease risk among children in Sweden. Scand J Public Health. 2014 Nov;42(7):572-80.
[4] Bao F. et al. One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies. J Autoimmun. 1999 Aug;13(1):143-8.
[5] Skaaby T. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. 2015 Feb 11.
[6] Kalliokoski S. et al. Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease. J Mol Med (Berl). 2015 Jan;93(1):51-62.
[7] Moon C. et al. Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature. 2015. Feb 16.
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Emilsson L, Wijmenga C, Murray JA, & Ludvigsson JF (2015). Autoimmune Disease in First-degree Relatives and Spouses of Individuals with Celiac Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association PMID: 25645875
Olivares M, Neef A, Castillejo G, Palma GD, Varea V, Capilla A, Palau F, Nova E, Marcos A, Polanco I, Ribes-Koninckx C, Ortigosa L, Izquierdo L, & Sanz Y (2014). The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. Gut PMID: 24939571
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