There’s was probably one kid in your class who always got strep throat. It seemed like they were out every few months like clockwork, often for days at a time. Maybe you were that kid. Immunologists have known about this phenomenon for a long time—some children are just prone to getting strep repeatedly. But until recently, they had no idea why.
That’s finally starting to change.
A team of immunologists, pediatric physicians, and infectious disease researchers at the La Jolla Institute for Immunology and University of California, San Diego decided to look more carefully at the immune responses different kids had to strep infections. What they found suggests that there are some genetic factors that determine whether a child is likely to get it recurrently. They published their results in Science Translational Medicine on Wednesday.
“Our work is the first attempt to answer why some children get [recurrent tonsillitis] and others do not,” says Shane Crotty, an immunologist and infectious disease researcher at both La Jolla and UCSD, who was a lead author on the study. He says there are likely other factors that contribute to recurrent cases, like which strains of strep are circulating in certain areas or whether a person lives in close quarters with others. But Crotty and his colleagues focused on the genetic aspects of the phenomenon.
First, a quick refresher on what strep throat actually is. Roughly 600 million people a year worldwide get infected with group A Streptococcus, or Streptococcus pyogenes, which is a bacterium that causes your tonsils to swell up, often accompanied by a fever. It’s painful (and can be dangerous if left untreated), but antibiotics usually clear it right up. In some kids, though, it keeps coming back. Physicians call this recurrent tonsillitis, and they’re interested in figuring out what causes it because, well, you know how often the strep throat kid was out of school. On top of missing out on important education, children who get recurrent tonsillitis also have to take many bouts of antibiotics, which isn’t great for the current antibiotic resistance problem or for their gut flora. The problem was that no one knew what made certain kids so prone to multiple infections.
The Ja Jolla-UCSD team thought it might have something to do with the tonsils themselves. Tonsils are part of your immune system, which is why they swell during an infection just like lymph nodes do (that’s because of all the immune cells rushing in to try to heal you). Their job is to help identify incoming pathogens and raise the alarm if there’s an intruder. Certain types of infections tend to centralize in the tonsils, and strep is one of them. It follows that if some kids aren’t able to get rid of a strep infection (or keep getting infected over and over again), that maybe their tonsils aren’t working properly.
And that’s exactly what the researchers found.
They started by gathering a group of kids in the San Diego area who had recurrent tonsillitis, matched them with similar children who got normal tonsillitis, then looked at various markers for their immune systems to see what differed between the two groups. (As an interesting side note, about 75 percent of the kids with recurrent infections were female, even though it was 50-50 in the non-recurrent group. Crotty says he doesn’t have any explanation for why that was, but that it’s certainly interesting and should be investigated further.) The study got into a lot of detail about the specific types of cells involved in mounting the body’s response to strep, but we’re going to simplify it down a bit for you. Basically, tonsils have sites inside them called germinal centers, which produce and mature different types of immune cells that are crucial for identifying pathogens. Given how frequently the kids with recurrent tonsillitis had strep infections (12 times more, to be exact), you’d expect to find more evidence of an immune response to Streptococcus—for example, you’d think those kids would have a lot more antibodies against strep. But these researchers found that children with recurring infections actually have less of a response, not more.
That suggests kids with recurrent tonsillitis have germinal centers that aren’t functioning properly in the face of a strep invasion, and perhaps that immunodeficiency is what’s driving the repeated infections. These kids also tend to have family members who have had tonsillectomies, which raises the possibility that there’s some genetic component to this germinal center problem. So the researchers looked at genes for the human leukocyte antigen. The HLA genes do a lot, but in part they determine what kinds of proteins your immune cells produce, and therefore what types of invaders it identifies as foreign. And they’re crucial determinants for how you respond to a streptococcal infection.
Children who had the most deficient germinal center responses also tended to have two particular HLA alleles (DRB101:01 and DRB107:01) at much higher frequencies than kids who didn’t get recurrent infections (as well as compared to the general population). All of this indicates that some kids are, from birth, less capable of developing immunity to group A Streptococcus the way most other children can. As noted in the paper, almost everyone gets exposed to the bacteria during childhood, so this difference in the ability to mount a proper response to the infection is likely (in part) what drives the difference in re-infection rates.
This is just the first step to understanding recurrent strep, but it could turn out to be helpful in screening kids who end up with repeated infections. “At this time, we are not advocating for HLA screening for all children,” Crotty says. “The most likely scenario is that this information will be useful in the future for children who present with having had multiple bouts of strep already. HLA typing may then be helpful in deciding if a patient would likely benefit from a tonsillectomy.”
