Why your child's strep throat continues to come back

Every year, some 600 million people worldwide contract strep throat. But for some children (and their parents), it's more than occasional misery. It's a recurring nightmare. However, it was difficult to understand why some children are prone to repeated episodes of strep throat while others seem more or less immune. The latest study by researchers at the La Jolla Institute of Immunology (LJI) provides early clues as to why some children are more likely than others to contract streptococcal tonsillitis. recurrent group A, better known as strep throat.

Their findings, published in the January 6, 2019 issue of Science Translational Medicine, suggest that relapsing tonsillitis is a multifactorial disease in which immunologic factors combined with underlying genetic susceptibility allow group A streptococcus to develop. repeatedly invading the throats of some individuals. Better understanding why some children do not develop protective immunity also opens the door to developing a vaccine against strep throat, according to the researchers.

"We have more than 100 years of experience with this disease, but nothing really explains why some children have strep throat recurrence," says lead author Shane Crotty, PhD, professor at the University of Toronto. Division of Vaccine Discovery. "We believe that this is the first strong evidence that there is an important immunologic component as well as a genetic component that together contribute to recurrence of angina." strep. Let's try to build on it. "

"Repetitive angina is the second most common indication for tonsillectomy in children. Like all surgical procedures, it carries some risks, but recent evidence suggests that tonsillectomy may increase the risk of upper respiratory disease in the long term, "said pediatric otolaryngologist and co-author, Matt Brigger, MD, chief of the Division of Otorhinolaryngology at Rady Children's Hospital in San Diego. "My hope is that if we learn more about the causes of repetitive streptococcal infections, we can intervene before they happen."

Strep throat is one of many conditions caused by the bacterium Streptococcus pyogenes, better known as Group A Streptococcus (GAS). It can cause pneumonia, scarlet fever, impetigo, which causes extremely infectious skin lesions and necrotizing fasciitis, the dreaded disease that nourishes the flesh. Unlike necrotizing fasciitis, strep throat is easily treated with antibiotics. But if you do not diagnose it, it can also lead to serious complications.

"Here in the US, we rarely see the consequences of untreated GAS infections," says physician and infectious disease specialist Jennifer Dan, first author. Dan holds a clinical badociate position at LJI, which allows him to split his time between visiting patients at UC San Diego and advanced research in the Crotty lab. "However, recurrent strep throat is a major concern in developing countries as children who are not receiving antibiotics are at real risk of developing rheumatic fever or rheumatic heart disease, a leading cause of heart disease." acquired among the young adults of the world. "

In trying to understand the long-standing mystery of why some children are prone to frequent tonsillitis attacks and what their immune response looks like, the researchers turned to the tonsils. The tonsils are structures resembling lymph nodes located on each side of the back of the throat. Small pockets, or crypts, on their surface, collect and sample microbes and can become fertile ground for GAS.

Dan removed tonsil tissue from a cohort of children aged 5 to 18, whose tonsils were removed, either because they had multiple episodes of throaty throat or when they were They had undergone tonsillectomy for unrelated reasons, such as sleep apnea. She was particularly interested in germinal centers, the central centers where B cells must team up with helper follicular T cells (Tfh cells) to start producing antibodies.

In addition to a significant decrease in the frequency of helper B cells and follicular helper T lymphocytes, the tonsils of children with recurrent tonsillitis generally exhibited ever smaller areas of germinal centers. "These kids have a bad germ center response," says Dan. "Interestingly, it is badociated with a particularly weak antibody response to SpeA, which is an important aspect of protective immunity."

Abbreviation for streptococcal pyrogenic exotoxin, SpeA is not an essential component of the GAS genome. However, a particularly potent version of the toxin appeared in the bacteria in the 1980s and these strains quickly swept the world to become the most common cause of strep throat. Children in the control group had high titers of anti-SpeA antibodies, which indicated that they had been exposed to the bacteria but had not become ill.

In children with recurrent GAS tonsillitis, the disease was likely to affect the family, suggesting a genetic component. Genetic testing revealed two specific genetic variants in the HLA region, which determine how pathogens interact with the immune system, which were badociated with increased susceptibility to recurrent tonsillitis and one that protected against the disease.

"Since the immunological link as well as the genetic link are all related to an insufficient antibody response against SpeA, this suggests that recognition of this factor is actually a key problem for these children," says Crotty. "Having a vaccine that drives the immune system in advance may be able to stimulate a protective immune response that can prevent recurring access to tonsillitis."

The work was funded in part by the La Jolla Institute of Immunology, a Thrasher research fund for an early career, the NIAID pediatric loan reimbursement program, the National Institute of Allergy and Immunity. Infectious Diseases (K08A135078, R01AI135193, R01AI077780), NIH Grant from the Center for Immunology Research on HIV / AIDS Vaccines (1UM1AI100663 and S10RR027366), National Institutes of Health (T32AI007036-35, T32AI007384-25, S10OD016262 , S10RR027366), Research Grant for the Development of Clinical Research, No. 1089464.

Reference: Jennifer M. Dan, Colin Havenar-Daughton, Kayla Kendric, Rita Al-Kolla, Kirti Kaushik, Sandy L. Rosales, Ericka L. Anderson, Christopher N. LaRock, Pandurangan Vijayanand, Gregory Seumois, David Layfield, Ramsey I. Cutress, Christian H. Ottensmeier, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Victor Nizet, Marcella Bothwell, Matthew Brigger and Shane Crotty. "Group A recurrent streptococcal tonsillitis is an immunosusceptible disease involving deficiency of antibodies and abnormal follicular T helper cells." Science Translational Medicine, 2019.

Source: Institute of Immunology La Jolla