Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity, 2018, Bjorkstrom et al

Andy · Jun 11, 2018

Abstract

Diversity is a central requirement for the immune system’s capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown. Here we study NK cell functional diversification in chronic hepatitis C virus (HCV) infection.

High-dimensional flow cytometer assays combined with stochastic neighbor embedding analysis reveal that chronic HCV infection induces functional imprinting on human NK cells that is largely irreversible and persists long after successful interventional clearance of the virus. Furthermore, HCV infection increases inter-individual, but decreases intra-individual, NK cell diversity. Taken together, our results provide insights into how the history of infections affects human NK cell diversity.
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Open access at https://www.nature.com/articles/s41467-018-04685-9

Article about the study

Changes to the immune system remain many years after a hepatitis C infection heals, a new study by researchers at Karolinska Institutet and Hannover Medical School shows. The findings, presented in Nature Communications, increases understanding about chronic infection and the way it regulates and impacts composition of the immune system.

Infection with hepatitis C virus (HCV) turns almost always chronic and poses a major health problem around the world. The infection can lead to cirrhosis and cancer of the liver when the immune system fails to fight the virus. Eventually the immune system becomes exhausted. Since a couple of years, however, most patients with HCV can now be cured in a matter of a few weeks with revolutionary new medications.
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https://ki.se/en/news/immune-system-does-not-recover-despite-cured-hepatitis-c-infection

Mij · Jun 11, 2018

The Canadian Association for the Study of the Liver, a national group of health-care providers and researchers, published its guidelines on testing and treating hepatitis C. It was in the news recently and it's recommended that testing should be for Canadians in a certain age bracket (born between 1945 and 1975).

I was tested many years ago to rule that out.

mariovitali · Sep 1, 2018

@Andy

Thank you for posting this paper.

cc : @JaimeS @Hip

In the link @Andy provided we read that Chronic Hepatitis C Infection impacts NK Cell diversity. Moreover in another paper we read that ME/CFS patients were found having low NK Cell Activity.

I found an interesting paper that connects TYRO3 (A Vitamin K-related Gene) with NK cell functions :

Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases.
Caraux A1, Lu Q, Fernandez N, Riou S, Di Santo JP, Raulet DH, Lemke G, Roth C.
Author information

Abstract
Although understanding of the function and specificity of many natural killer (NK) cell receptors is increasing, the molecular mechanisms regulating their expression during late development of NK cells remain unclear. Here we use representational difference analysis to identify molecules required for late NK cell differentiation. Axl protein tyrosine kinase, together with the structurally related receptors Tyro3 and Mer, were essential for NK cell functional maturation and normal expression of inhibitory and activating NK cell receptors. Also, all three receptors were expressed in maturing NK cells, the ligands of these receptors were produced by bone marrow stromal cells, and recombinant versions of these ligands drove NK cell differentiation in vitro. These results collectively suggest that Axl, Tyro3 and Mer transmit signals that are essential for the generation of a functional NK cell repertoire.
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Link can be found here

TYRO3 potential relevance has been found by Machine Learning Methods, here is a post from May 2017 :

http://algogenomics.blogspot.com/20...al&utm_source=twitter.com&utm_campaign=buffer

Professor @Jonathan Edwards Do you believe this may be relevant?

Amw66 · Sep 1, 2018

Interestingly my aunt had really bad Hep C in her youth....really bad ME now...

Milo · Sep 2, 2018

Mij said: ↑

The Canadian Association for the Study of the Liver, a national group of health-care providers and researchers, published its guidelines on testing and treating hepatitis C. It was in the news recently and it's recommended that testing should be for Canadians in a certain age bracket (born between 1945 and 1975).

I was tested many years ago to rule that out.
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It is because Canadian blood banks (also affecting blood products) did not test for Hep C during that time range and people may have been exposed to Hep C may it be from birth, or other mean of getting it (blood transfusion, blood-blood exposure such as sharing needles).

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Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity, 2018, Bjorkstrom et al

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