The study identifies a gene variant in Inuit that causes more severe reactions to infections

A global team of scientists has discovered a gene variant in Inuit that may be responsible for worse outcomes of viral infections.

People with gene deficiency do not produce certain types of interferons, which are proteins that fight infection. This can lead to serious illness when faced with certain viruses, such as measles, the flu, or COVID-19.

“If you have this variant, you will have a problem with viruses,” said Trine Mogensen, a biomedical researcher at Aarhus University in Denmark and lead author of the study. published in the Journal of Experimental Medicine.

“It’s an important risk factor.”

The findings are the result of a global network of researchers studying the cases of five Inuit children in Canada, Greenland and Alaska who were hospitalized with unusually severe viral infections.

View from Ilulissat, Greenland. Researchers estimate that about 1 in 1,500 Inuit is affected by the variant, based on samples from more than 4,600 Greenlanders and just over 100 Inuit from 10 communities in Nunavik. (Getty Images)

In two of the cases, children with a history of annoying infections were hospitalized with severe colds. But doctors found that few treatments were effective and that normally harmless childhood vaccines seemed to make things worse.

As their condition worsened, doctors discovered that they tested positive not for one but for several viral infections, from Epstein-Barr to chickenpox.

Two other cases involved children who developed high fevers and seizures within a few weeks of receiving a common childhood vaccine against measles, mumps, and rubella (MMR), which contains a weakened version of the virus. While both were recovering, one later died of a very rare COVID-19 infection in young children. The sister of one of these patients also became seriously ill with the flu, although she was able to receive the MMR vaccine without incident.

The researchers suspected there might be an underlying genetic explanation for why these children suffered from such unusually severe responses to common childhood viruses. When the children were tested, they found the previously undocumented genetic variant which meant that these children were worse equipped to fight infectious diseases.

1 in 1,500 Inuit affected

Researchers then searched a database of more than 4,600 Greenlanders and just over 100 Inuit from 10 communities in Nunavik to see how common the gene deficiency was.

It is estimated that about one in 1,500 Inuit are affected, which puts them at risk for severe reactions to COVID-19, the flu, and some common childhood vaccines because they cannot fight many viruses.

In comparison, the gene is virtually non-existent in other populations. The authors say more Inuit testing is needed to determine exactly how many may be affected.

Michael Patterson, Nunavut’s medical director of health, questioned the numbers in the document, saying the study did not provide enough data to form a “firm or reliable estimate.” He said more genetic samples are needed among Canadian Inuit to say “it is appropriate to start detecting this disease”.

Dr. Michael Patterson, Nunavut’s director of public health, says the figures in the study suggest that the variant would affect “one child every two years or so” in Nunavut. (Emma Tranter / The Canadian Press)

But other experts say the finding is not surprising.

“I was not surprised,” said Shirley Tagalik, president of the Aqqiumavvik Welfare Society in Arviat, Nunavut, and a longtime community researcher on Inuit health. “We’ve known for several years that Inuit children in particular may react differently to various vaccines.”

Anna Banerji, an expert on Indigenous health, pediatrics and infectious diseases at the Dalla Lana School of Public Health at the University of Toronto, was not surprised either. He has studied respiratory infections in Inuit babies for decades and found that they occur almost four times more often than in non-Inuiteven when environmental factors are controlled.

“I always believed there was a genetic component,” he said.

Shirley Tagalik, a longtime community health researcher and president of the Aqqiumavvik Welfare Society in Arviat, Nunavut, with her granddaughter Qaviajuk. Tagalik says the results of the study are not surprising, as he knows that Inuit children react differently to various vaccines. (Submitted by Shirley Tagalik)

Researchers point out that it should not raise doubts about the vaccine

One in 1,500 sounds like a lot of people, but among the relatively small Inuit population, it reaches about 100 Inuit worldwide and about 50 in Canada.

For this handful of people, a flu or COVID-19 infection is likely to result in hospitalization or death. There is also a serious risk of what are known as live virus vaccines, such as MMR and yellow fever, which use a weakened form of a particular virus to teach the body’s immune system how to respond when faced with reality. .

But experts point out that the findings should not make people suspicious of vaccines in general. First, many modern vaccines, such as the COVID-19 vaccine, carry no live virus and pose no risk to those with the gene variant.

The study, conducted by a global team led by Professor Trine Mogensen of Aarhus University in Denmark, found a gene variant in some Inuit that makes it difficult to fight viruses and certain childhood vaccines that contain live viruses. (Submitted by Trine Mogensen)

“All other childhood vaccines, the flu and COVID-19 vaccines” are still safe for those with the gene, Mogensen said.

Second, for those who do not have the variant, including the vast majority of Inuit, it is vital that live virus vaccines continue. Childhood immunizations, such as the MMR vaccine, have been instrumental in reducing the severity of the disease in the north, which has experienced devastating outbreaks of measles and tuberculosis just a generation ago.

“Some communities have become extinct because of these viruses,” Banerji said. “The worst thing we can begin to say is that we should not vaccinate Inuit babies because of this risk.”

Patterson encouraged parents to adhere to the routine vaccination schedule and stressed that even using the population estimates in the document, only about “one child every two years or so” would be affected.

“Avoiding vaccines for this would, for the vast majority of people, greatly increase the risk of serious infection.”

Dr. Anna Banerji, who studies Indigenous health, pediatrics, and infectious diseases at the Dalla Lana School of Public Health at the University of Toronto, says genetics has long been suspected to play a role in children’s susceptibility. inuit to infections. (Michael Cooper / University of Toronto)

Projection possible, but distant

As with many genetic disorders, it is possible to examine the deficiency even before a child is born, or along with tests for other disorders, such as cystic fibrosis, after childbirth.

Mogensen says children who are positive for the deficiency could be put on a course of antivirals to protect them from the worst childhood infections. She is working with pediatricians in Denmark to implement as soon as possible.

But Patterson said it is impossible to say when Nunavut Inuit could begin to be examined for the deficiency.

At this time, newborn babies in Nunavut are automatically screened for a variety of genetic disorders, which occur, although rarely, in both Inuit and non-Inuit. But labs that analyze these disorders “may or may not be able to test them easily,” Patterson said.

Mogensen and independent genetic testing labs contacted by CBC suggested otherwise. Aaron Goldman, scientific director of DNALabs Canada, said it would cost “a couple of thousand dollars at most” to redesign a test, and about $ 100 per sample after that. Compared to the cost of medical evacuations and hospitalizations, Mogensen says the screening is “cost-effective.”

An unmarried mother takes her baby to Shishmaref, Alaska. (Gabriel Bouys / AFP via Getty Images)

Banerji suggested that there is a “lack of political will” to deal with something that affects a small indigenous population.

“There is a systematic bias against indigenous people,” he said. “We are willing to find genetic testing for rare diseases where there is more than one lobby.”

Tagalik, Arviat’s community health researcher, said the document presented “a minefield” to health authorities. Implementing a screening program, or even collecting more data, would require “purchase, commitment, and agreement not only from the people above and the people below, but from all the people involved.”

In the past, he has seen his own recommendations on child health hampered by government protests over cost, community leadership rotation, and medical facility objections.

“Nothing will move forward if you don’t have the government behind you,” he said, “and even if you have the government behind you, that’s not enough.”

Unique among Inuit

Although the gene variant, known as IFNAR2 deficiency, has only been documented in Inuit, the researchers also found a similar variant, which affected the IFNAR1 gene. in the western Polynesians in a parallel study.

Researchers attribute this similarity to the relatively isolated existence of these communities for much of their history. It may also be one reason why outbreaks of infectious diseases, such as measles and tuberculosis, were so devastating to these communities.

“We believe that some of these serious infections, which were thought to be meningitis or tuberculosis, may have been due to this defect,” Mogensen said.

Inuit have not often been the subject of genetic studies, in part because projects to map the human genome have historically focused on Caucasian populations.

A group of Inuit children play with a puppy in Gjoa Haven, Nunavut, in 2013. (Sean Kilpatrick / The Canadian Press)

“We have a biased map of the genome,” Mogensen said. “We’ve been doing gene sequencing for just over 20 years, and most patients are …

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