Treatment for lupus

Science has trends, like everything else. Some are longer or shorter lived, depending on how many astonishing discoveries are linked to that given subject. The 2000’s were unquestionably the years of the DNA. Many a grant have been written (and granted) for whole-genome surveys of this and that. Alternative splicing followed. The ’10s saw the rise of various -omics: transcriptomics, metabolomics, proteomics etc. Then everybody and his mamma got on the cart of epigenetics. With a side of immune stuff. Now, move aside epigenetics, here comes the microbiome. And CRISPR.

That is not to say that the not so hip subjects of the bygone years are thoroughly squeezed of knowledge and we throw them aside like some dry dead end and never touch them again. Not at all, not a bit. The trends only mark the momentary believes of the purse holders about which direction the next panaceum universalis will jump from.

Here comes a groundbreaking paper on the gut microbiome. It’s groundbreaking because it comes with a cure for systemic lupus erythematosus (SLE). Possibly autoimmune hepatitis and others autoimmune diseases as well.

An autoimmune disease is a terrible malady that is often incurable and sometimes deadly. It happens when the immune system starts attacking the body. One hypothesis as to why that happens posits that after a particular infection, maybe a particularly nasty one, the immune system doesn’t stop attacking, but now in the absence of an enemy it turns on its own body in genetically susceptible individuals.

Vieira et al. (2018) worked with genetically susceptible mice. And the bombshell comes right there in the first page: after treatment with an oral antibiotic (vancomycin or ampicillin, but not neomycin), mice genetically designed to develop lupus had lower “mortality, lupus-related autoantibodies, and autoimmune manifestations” (p. 1156). Then the researchers took a closer look at the bodies of these mice and observed that 82% of the mice had spleens and livers infected with Enterococcus gallinarum, a gut bacterium that should stay in the gut. But this bacterium is capable of weakening the gut barriers by loosening the tightness of the junctions between gut cells and then migrate to liver, spleen, and lymph nodes. Its high abundance in these places triggers a systemic immune response. Then the authors force-fed some germ-free mice with E. galinarum and saw that the mice developed systemic autoimmune pathology.

As if that’s not enough of a news story, the researchers developed a vaccine against this bacterium. The vaccine is very specific (being made of heat-killed E. gallinarum) and results in reduced levels of serum autoantibodies and prolonged survival rate in the lupus-prone mice.

So people don’t quibble, and rightly so, that those are rodents and humans are not (well, most of them, anyway), the authors looked at the liver biopsies of three humans with SLE and five with autoimmune hepatitis (AIH). They were positive for E. gallinarum, but the controls, i. e. healthy humans, were not. Also, when healthy human liver cells were stimulated with E. gallinarum they displayed autoimmune responses, just like in the murine cells. Finally, you don’t have to undergo a liver biopsy to see if you’re infected with E. gallinarum, just a specific blood test to see if you have increased antibody titers against this bug (or its RNA) as most SLE and AIH patients did.

Needless to say, I am extremely happy with this paper. Who wouldn’t be?! It’s a cure paper! I know, I know, they don’t say that, but what does this sound to you?:

“Administration of oral vancomycin or an intramuscular vaccine against E. gallinarum prevent translocation, Th17/Tfh cell induction, autoantibody production and autoimmune-related mortality (Supplemental, p. 62).”

Call it a very promising cure or a highly effective treatment if you like, but it stares you in the face for what it is as it did the researchers who already patented their stuff and are currently conducting clinical trials.

Most of the paper is in the Supplemental material, not in the 4 pages and a bit in Science. So even if the paper is under the paywall, the Supplementals are not. Be ready for a 71 page worth of 167 MB of data though.

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REFERENCE: Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA (9 Mar 2018). Translocation of a gut pathobiont drives autoimmunity in mice and humans.  Science, 359(6380):1156-1161. doi: 10.1126/science.aar7201. PMID: 29590047, DOI: 10.1126/science.aar7201. ARTICLE |  Supplemental Material | Yale press release

By Neuronicus, 8 April 2018

No Link Between Mass Shootings & Mental Illness

On Valentine’s Day another horrifying school mass shooting happened in USA, leaving 17 people dead. Just like after the other mass shootings, a lot of people – from media to bystanders, from gun lovers to gun critics, from parents to grandparents, from police to politicians – talk about the link between mental illness and mass shootings. As one with advanced degrees in both psychology and neuroscience, I am tired to explain over and over again that there is no significant link between the two! Mass shootings happen because an angry person has had enough sorrow, stress, rejection and/or disappointment and HAS ACCESS TO A MASS KILLING WEAPON. Yeah, I needed the caps. Sometimes scientists too need to shout to be heard.

So here is the abstract of a book chapter called straightforwardly “Mass Shootings and Mental Illness”. The entire text is available at the links in the reference below.

From Knoll & Annas (2015):

“Common Misperceptions

  • People with serious mental illness should be considered dangerous.
  • Gun laws focusing on people with mental illness or with a psychiatric diagnosis can effectively prevent mass shootings.
  • Gun laws focusing on people with mental illness or a psychiatric diagnosis are reasonable, even if they add to the stigma already associated with mental illness.

Evidence-Based Facts

  • Mass shootings by people with serious mental illness represent less than 1% of all yearly gun-related homicides. In contrast, deaths by suicide using firearms account for the majority of yearly gun-related deaths.
  • The overall contribution of people with serious mental illness to violent crimes is only about 3%. When these crimes are examined in detail, an even smaller percentage of them are found to involve firearms.
  • Laws intended to reduce gun violence that focus on a population representing less than 3% of all gun violence will be extremely low yield, ineffective, and wasteful of scarce resources. Perpetrators of mass shootings are unlikely to have a history of involuntary psychiatric hospitalization. Thus, databases intended to restrict access to guns and established by guns laws that broadly target people with mental illness will not capture this group of individuals.
  • Gun restriction laws focusing on people with mental illness perpetuate the myth that mental illness leads to violence, as well as the misperception that gun violence and mental illness are strongly linked. Stigma represents a major barrier to access and treatment of mental illness, which in turn increases the public health burden”.

REFERENCE: Knoll, James L. & Annas, George D. (2015). Mass Shootings and Mental Illness. In book: Gun Violence and Mental Illness, Edition: 1st, Chapter: 4, Publisher: American Psychiatric Publishing, Editors: Liza H. Gold, Robert I. Simon. ISBN-10: 1585624985, ISBN-13: 978-1585624980. FULLTEXT PDF via ResearchGate | FULLTEXT PDF via Psychiatry Online

The book chapter is not a peer-reviewed document, even if both authors are Professors of Psychiatry. To quiet putative voices raising concerns about that, here is a peer-reviewed paper with open access that says basically the same thing:

Swanson et al. (2015) looked at large scale (thousands to tens of thousands of individuals) data to see if there is any relationship between violence, gun violence, and mental illness. They concluded that “epidemiologic studies show that the large majority of people with serious mental illnesses are never violent. However, mental illness is strongly associated with increased risk of suicide, which accounts for over half of US firearms–related fatalities”. The last sentence is reminiscent of the finding that stricter gun control laws lower suicide rate.

REFERENCE: Swanson JW, McGinty EE, Fazel S, Mays VM (May 2015). Mental illness and reduction of gun violence and suicide: bringing epidemiologic research to policy. Annals of Epidemiology, 25(5): 366–376. doi: 10.1016/j.annepidem.2014.03.004, PMCID: PMC4211925. FULLTEXT | FULLTEXT PDF.

Further peer-reviewed bibliography (links to fulltext pdfs):

  1. Guns, anger, and mental disorders: Results from the National Comorbidity Survey Replication (NCS-R): “a large number of individuals in the United States have anger traits and also possess firearms at home (10.4%) or carry guns outside the home (1.6%).”
  2. News Media Framing of Serious Mental Illness and Gun Violence in the United States, 1997-2012: “most news coverage occurred in the wake of mass shootings, and “dangerous people” with serious mental illness were more likely than “dangerous weapons” to be mentioned as a cause of gun violence.”
  3. The Link Between Mental Illness and Firearm Violence: Implications for Social Policy and Clinical Practice: “Firearm violence is a significant and preventable public health crisis. Mental illness is a weak risk factor for violence despite popular misconceptions reflected in the media and policy”.
  4. Using Research Evidence to Reframe the Policy Debate Around Mental Illness and Guns: Process and Recommendations: “restricting firearm access on the basis of certain dangerous behaviors is supported by the evidence; restricting access on the basis of mental illness diagnoses is not”.
  5. Mental Illness, Mass Shootings, and the Politics of American Firearms: “notions of mental illness that emerge in relation to mass shootings frequently reflect larger cultural stereotypes and anxieties about matters such as race/ethnicity, social class, and politics. These issues become obscured when mass shootings come to stand in for all gun crime, and when “mentally ill” ceases to be a medical designation and becomes a sign of violent threat”.

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By Neuronicus, 25 February 2018

Old chimpanzees get Alzheimer’s pathology

Alzheimer’s Disease (AD) is the most common type of dementia with a progression that can span decades. Its prevalence is increasing steadily, particularly in the western countries and Australia. So some researchers speculated that this particular disease might be specific to humans. For various reasons, either genetic, social, or environmental.

A fresh e-pub brings new evidence that Alzheimer’s might plague other primates as well. Edler et al. (2017) studied the brains of 20 old chimpanzees (Pan troglodytes) for a whole slew of Alzheimer’s pathology markers. More specifically, they looked for these markers in brain regions commonly affected by AD, like the prefrontal cortex, the midtemporal gyrus, and the hippocampus.

Alzheimer’s markers, like Tau and Aβ lesions, were present in the chimpanzees in an age-dependent manner. In other words, the older the chimp, the more severe the pathology.

Interestingly, all 20 animals displayed some form of Alzheimer’s pathology. This finding points to another speculation in the field which is: dementia is just part of normal aging. Meaning we would all get it, eventually, if we would live long enough; some people age younger and some age older, as it were. This hypothesis, however, is not favored by most researchers not the least because is currently unfalsifiable. The longest living humans do not show signs of dementia so how long is long enough, exactly? But, as the authors suggest, “Aβ deposition may be part of the normal aging process in chimpanzees” (p. 24).

Unfortunately, “the chimpanzees in this study did not participate in formal behavioral or cognitive testing” (p. 6). So we cannot say if the animals had AD. They had the pathological markers, yes, but we don’t know if they exhibited the disease as is not uncommon to find these markers in humans who did not display any behavioral or cognitive symptoms (Driscoll et al., 2006). In other words, one might have tau deposits but no dementia symptoms. Hence the title of my post: “Old chimpanzees get Alzheimer’s pathology” and not “Old chimpanzees get Alzheimer’s Disease”

Good paper, good methods and stats. And very useful because “chimpanzees share 100% sequence homology and all six tau isoforms with humans” (p. 4), meaning we have now a closer to us model of the disease so we can study it more, even if primate research has taken significant blows these days due to some highly vocal but thoroughly misguided groups. Anyway, the more we know about AD the closer we are of getting rid of it, hopefully. And, soon enough, the aforementioned misguided groups shall have to face old age too with all its indignities and my guess is that in a couple of decades or so there will be fresh money poured into aging diseases research, primates be damned.

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REFERENCE: Edler MK, Sherwood CC, Meindl RS, Hopkins WD, Ely JJ, Erwin JM, Mufson EJ, Hof PR, & Raghanti MA. (EPUB July 31, 2017). Aged chimpanzees exhibit pathologic hallmarks of Alzheimer’s disease. Neurobiology of Aging, PII: S0197-4580(17)30239-7, DOI: ABSTRACT  | Kent State University press release

By Neuronicus, 23 August 2017



Midichlorians, midichloria, and mitochondria





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By Neuronicus, 29 July 2017

Aging and its 11 hippocampal genes










By Neuronicus, 25 January 2017



Don’t eat snow










By Neuronicus, 26 December 2016



Soccer and brain jiggling











By Neuronicus, 20 December 2016

Amusia and stroke









unless you’re left-handed, then things are reversed.




By Neuronicus, 9 November 2016


Another puzzle piece in the autism mystery


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By Neuronicus, 31 August 2016

One parent’s gene better than the other’s

Not all people with the same bad genetic makeup that predisposes them to a particular disease go and develop that disease or, at any rate, not with the same severity and prognosis. The question is why? After all, they have the same genes…

Here comes a study that answers that very important question. Eloy et al. (2016) looked at the most common pediatric eye cancer (1 in 15,000) called retinoblastoma (Rb). In the hereditary form of this cancer, the disease occurs if the child carries mutant (i.e. bad) copies of the RB1 tumour suppressor gene located on chromosome 13 (13q14). These copies, called alleles, are inherited by the child from the mother or from the father. But some children with this genetic disadvantage do not develop Rb. They should, so why not?

The authors studied 57 families with Rb history. They took blood and tumour samples from the participants and then did a bunch of genetic tests: DNA, RNA, and methylation analyses.

They found out that when the RB1 gene is inherited from the mother, the child has only 9.7% chances of developing Rb, but when the gene is inherited from the father the child has only 67.5% chances of developing Rb.

The mechanism for this different outcomes may reside in the differential methylation of the gene. Methylation is a chemical process that suppresses the expression of a gene, meaning that less protein is produced from that gene. The maternal gene had less methylation, meaning that more protein was produced, which was able to offer some protection against the cancer. Seems counter-intuitive, you’d think less bad protein is a good thing, but there is a long and complicated explanation for that, which, in a very simplified form, posits that other events influence the function of the resultant protein.

Again, epigenetics seem to offer explanations for pesky genetic inheritance questions. Epigenetic processes, like DNA methylation, are modalities through which traits can be inherited that are not coded in the DNA itself.

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Reference: Eloy P, Dehainault C, Sefta M, Aerts I, Doz F, Cassoux N, Lumbroso le Rouic L, Stoppa-Lyonnet D, Radvanyi F, Millot GA, Gauthier-Villars M, & Houdayer C (29 Feb 2016). A Parent-of-Origin Effect Impacts the Phenotype in Low Penetrance Retinoblastoma Families Segregating the c.1981C>T/p.Arg661Trp Mutation of RB1. PLoS Genetics, 12(2):e1005888. eCollection 2016. PMID: 26925970, PMCID: PMC4771840, DOI: 10.1371/journal.pgen.1005888. ARTICLE | FREE FULLTEXT PDF

By Neuronicus, 24 July 2016