Pediatric autoimmune diseases: Finding hope in research

Jamee Emens, the mother of triplets, remembers the sleepless nights all too well. For years, her son Jack battled a vicious cycle of respiratory issues while his sisters, Cameron and Peyton, faced other health issues. Jack was just 2 years old when he was diagnosed with reactive airway disorder, a condition that escalated into severe asthma. By the time he turned 5, Jack was trapped in a routine of dry coughs, difficulty breathing and emergency hospital visits. 

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“I’d sit with him in the bathroom, steam filling the room, just hoping his breathing would ease up,” Jamee said. “We’d use a nebulizer every few hours, but nothing seemed to work for long. Eventually, we’d rush him to the ER, where he’d spend days recovering on oxygen and steroids, only for the cycle to start all over again a week later.”

For eight long years, Jack endured the same painful pattern.

“Every two to three weeks, we’d go through the same terrifying routine,” Jamee said. “It felt endless.”

Everything changed in 2013, when Jamee’s father met Fayez K. Ghishan, MD, the PANDA endowed director of the University of Arizona Steele Children’s Research Center and Alan and Janice Levin Family endowed professor and head of the Department of Pediatrics at the U of A College of Medicine – Tucson. A few days later, Jamee found herself sitting across from Ghishan, who would alter the course of her son’s life forever.

“He listened carefully, examined Jack and said, ‘I think he has eosinophilic esophagitis, but I’ll need to do an endoscopy to be sure,’” Jamee recalled. 

The diagnosis of eosinophilic esophagitis, an allergic condition that occurs when the esophagus becomes inflamed and does not contract properly, was confirmed. With a few simple dietary changes prescribed by Ghishan, Jack’s unbreakable cycle of respiratory distress came to an end. 

Jack’s story is far from unique. Autoimmune diseases affect millions of people worldwide, and their prevalence is increasing. To help families like the Emenses, the Steele Children’s Research Center and the U of A Health Sciences Center for Advanced Molecular and Immunological Therapies are leading novel research to advance the diagnosis, prevention and treatment of autoimmune diseases.

Understanding autoimmune diseases

In the United States alone, more than 40 million people suffer from over 100 different autoimmune diseases. These conditions occur when the body’s immune system mistakenly attacks healthy cells, leading to inflammation and damage in various organs and tissues.

“There are two types of inflammation: infectious, where you have bacteria or viruses causing an immune response, and sterile, where the immune system attacks the body’s own tissues for no apparent reason. This latter type is what we see in autoimmune diseases,” Ghishan said. 

Autoimmune diseases vary widely in their effects. Rheumatoid arthritis causes joint pain; Crohn’s disease and ulcerative colitis impact the digestive system; Conditions such as asthma and atopic dermatitis affect the lungs and skin. 

“Asthma, for example, is an autoimmune disease,” Ghishan said. “People don’t often think of it that way, but it’s the immune system that’s causing the inflammation in the airways.”

A key component in the development of autoimmune diseases is the interaction between genetics and environmental factors, also known as epigenetics. 

“Diet and lifestyle, combined with genetics, are the cause of autoimmunity.” — Fayez K. Ghishan, MD

“Epigenetics means environmental factors drive changes in the function of the gene rather than the structure of the gene,” Ghishan explained. “The genes are the genes. They are not changing. You have 23,000 genes in your body, and they are stable; however, their function can be changed by the environment.”

Once an individual has one autoimmune disease, they are more likely to develop others. Ghishan said this makes it critical for doctors to regularly screen patients for additional autoimmune diseases. 

“With Type 1 diabetes patients, for example, every year we screen them for thyroid function and celiac disease,” he said. “The problem is, some doctors think that if they tested last year and it was negative, it will stay that way. But that’s wrong. Autoimmune diseases can emerge over time, so patients must be checked annually.”

The role of the microbiome

Another critical factor in the development of autoimmune diseases is the gut microbiome – the trillions of bacteria living in our digestive systems that play a prominent role in regulating immune function. 

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“We are a superorganism,” Ghishan said. “The number of organisms in our gut is more than the stars in the universe, more than the cells in our body.” 

Ghishan explained that these bacteria, when healthy and balanced, work in harmony with the body, but environmental disruptions caused by poor diet, stress or overuse of antibiotics can trigger autoimmune responses.

“If the microbiome changes in a bad way, the risk of autoimmune diseases increases dramatically,” he said. “The more you eat fast food, for example, the more likely you’ll change your gut microbiome in a bad way. The more sedentary you are, the higher the incidence of autoimmunity. So, diet and lifestyle, combined with genetics, are the cause of autoimmunity.”

Ghishan is a co-author on a paper that was published in the journal Gut Microbes in March. The paper further emphasized how much influence the gut microbiome has in the development of autoimmune diseases. In the study, the research team transferred gut bacteria from patients with Crohn’s disease into germ-free mice. Those mice soon developed inflammation indicative of Crohn’s disease.

“This suggests that the gut microbiome plays a major role,” Ghishan said. 

Promoting a healthy microbiome from early life is essential, according to Ghishan, who said the first 1,000 days of life, from conception to 2 years old, are particularly critical. 

“If we can promote a diverse microbiome during this time, through breastfeeding, natural childbirth and a healthy diet, we can significantly reduce the risk of autoimmune diseases later in life,” he said. 

Giving families hope for the future

Jack’s journey was only part of the tribulations for Jamee and her husband, Chris. Indicative of the role genetics play in autoimmune diseases, all three siblings were diagnosed with multiple chronic conditions at various points of their lives. Cameron was the first to experience symptoms when her eye began to droop at 18 months old, and she was eventually diagnosed with myasthenia gravis. Diagnoses for Type 1 diabetes, vitiligo, Hashimoto’s disease, eosinophilic esophagitis, autonomic dysfunction and Renaud’s disease followed for the triplets over the years.

Today, Jamee knows what she did not know 18 years ago: that whole genome sequencing could have diagnosed each of her children with their various autoimmune diseases at an early age. Whole genome sequencing is a process that involves analyzing a person’s DNA to understand the genetic factors that contribute to diseases. 

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“We collect DNA from a blood sample or, for children, from a simple cheek swab,” Ghishan said. “The DNA is then broken into smaller pieces, and we use special machines to read and analyze every part of it.”

Once the DNA is sequenced, powerful computers compare the data to a reference genome to find any mutations or pathogenic variants. To make the results easier for doctors to use, the data is organized into panels, or specific sets of genes related to particular conditions, such as liver or kidney diseases. This approach helps doctors pinpoint the cause of a disease more quickly and create personalized treatments that target the patient’s unique genetic makeup.

In 2022, the Steele Children’s Research Center became the first academic entity in Arizona to obtain a machine that allows for cost-effective, large-scale whole-genome sequencing. The Phoenix Women's Board of the Steele Children's Research Center, affectionately known as PANDA (People Acting Now Discover Answers), raised the funds to purchase the new sequencer.

That same year, a $10 million gift from the Steele Foundation was made to establish the Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research and provide financial support for graduate students, postdoctoral researchers and faculty members. Of the gift, $2 million was designated for the Center for Advanced Molecular and Immunological Therapies. 

For the Emens family and others, these advancements in research and technology mean a future filled with hope that precision medicine will bring better, faster and personalized diagnoses and treatments for all autoimmune conditions. 

“Knowing that other families might not have to endure what we did is comforting,” Jamee said.