Research We Fund

A Brighter Future for Children with Neuroimmunological Conditions

at the Neuroscience and Behavioral Medicine Center of Children's National Hospital

Principal Investigator: Elizabeth Wells, MD

Background:

Pediatric neuroimmunological conditions are a group of neurologic disorders predominantly characterized by inflammatory responses in the central nervous system and are autoimmune in nature. In children with these autoimmune conditions, the body’s natural defense system attacks its own healthy cells. Neuroimmunological conditions specifically target the brain and nervous system. Many of these complete conditions are idiopathic and arise spontaneously, leaving previously healthy children with a lifetime of illness and challenges. Neuroimmunological conditions can affect a child’s ability to eat, walk, talk, think, see or move normally.

Children’s National Hospital is home to one of the few comprehensive pediatric neuroimmunology programs in the country and some of the nation’s leading Neuroimmunology experts. Their specialists have expertise in caring for children with a wide range of neuroimmunological conditions, including autoimmune encephalitis, neuromyelitis optica spectrum disorder (NMO or NMOSD), multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody disease (MOG or MOGAD), acute disseminated encephalomyelitis (ADEM), opsoclonus-myoclonus-ataxia syndrome (OMAS), primary CNS vasculitis, transverse myelitis, acute flaccid myelitis (AFM), new-onset refractory status epilepticus (NORSE), and febrile infection-related epilepsy syndrome (FIRES).

Research Aims:

To develop and implement new investigative studies and clinical trials for children with neuroimmunological conditions. More specifically:

1. Identify shared immune dysregulatory pathways in patients with immune-neurologic conditions

2. Discover potential genetic causes of clinically characterized but genetically uncharacterized neuro-inflammatory diseases

3. Characterize the clinical disease manifestations to generate a comprehensive assessment of neurological and non-neurological disease indicators, and

4. Collect longitudinal functional outcomes, including neurologic status, functional status, neurocognitive outcomes, and quality of life.

Dr. Elizabeth Wells, M.D.

Long Covid (PASC) Study

at the Čiháková Research Laboratory at John Hopkins

Principal Investigator: Daniela Čiháková, MD

Background:

Acute SARS-CoV-2 infection (COVID-19) is associated with both high cardiovascular morbidity and mortality. After an acute infection, some patients fail to fully recover and suffer for an extended period of time. Commonly referred to as “Long Covid,” this phenomenon is technically called Post-Acute Sequelae of SARS-CoV-2 (PASC). PASC is characterized by a high prevalence of persistent cardiac symptoms (such as chest pain, shortness of breath, arrhythmias, and decreased cardiac function). Remarkably, more than 25% of patients hospitalized with COVID-19 are found to have myocardial injury. However, the extent to which immune responses—such as myeloid cells, lymphocytes, and cytokines—may contribute to cardiovascular involvement in acute COVID-19 and in PASC is unknown. The duration of cardiovascular morbidity in PASC patients is also unknown.

The immune profile of patients with cardiovascular PASC is understudied. To date, there have been no long-term studies investigating systemic markers in patients with PASC. Consequently, there is a need to understand the determinants of cardiovascular sequelae along the acute COVID-19 to PASC disease spectrum with attention to the immune profile.

Research Aims:

Daniela Čiháková, M.D., Ph.D., has assembled a team of cardiologists, virologists, and experts in animal modeling at Johns Hopkins to collaborate with her on this project. The team will examine sera and immune cells from the blood of patients that were seen at the Johns Hopkins’ Long Covid clinic. These samples will be compared to healthy controls and samples from patients who tested positive for Covid in the past but completely recovered. The samples will undergo immunological, clinical, and imaging assessments.

Daniela Čiháková, M.D., Ph.D.

Cancer Therapy Induced Autoimmune Myocarditis Study

at the Čiháková Research Laboratory at John Hopkins

Principal Investigator: Daniela Čiháková, MD

Background:

Myocarditis is an inflammatory disease of the heart muscle cells, and myocarditis is most often caused by a viral infection. Giant cell myocarditis and eosinophilic myocarditis are rare but particularly severe types of myocarditis. About 30% of myocarditis survivors develop dilated cardiomyopathy (an enlargement and weakening of the heart muscle), one of the most common reasons for heart transplantation in all ages.

Immune checkpoint inhibitors (ICI) have transformed the treatment of a wide spectrum of cancers. These therapies target molecules called “programmed cell death protein 1” (PD-1) and its ligand (PD-L1) (anti-PD-1/PD-L1 therapy). However, this new cancer therapy can lead to immune-related adverse events when autoimmune inflammation affects various organs. Immune-related adverse events are typically not life-threatening and manageable. However, autoimmune myocarditis has emerged as a rare but fatal complication of ICI therapies. Mortality for this ICI-associated myocarditis is high—50% of affected patients died.

Research Aims:

Dr. Čiháková’s team will investigate the protective mechanism of the PD-1/PD-L1 interaction in the myocardium (the cardiac source of PD-L1 that protects the heart from myocarditis), the ability of the PD-1/PD-L1 pathway to prevent myocarditis progression to dilated cardiomyopathy, and the therapeutic potential of forced PD-L1 overexpression in myocarditis/dilated cardiomyopathy treatment.

Characterizing the Autoantibody and Genetic Profiles of Patients with Multiple Autoimmune Conditions

at Boston Children's Hospital

Principal Investigators: Jocelyn Silvester, MD, Ph.D. and Denis Chang, MD, MS.

Background:

The research team at Boston Children’s Hospital will use blood samples to simultaneously test for multiple autoantibodies associated with many different autoimmune conditions using autoantigen microarray panels. Utilizing this technology, the team will investigate whether there are identifiable autoantibody signatures that can distinguish individuals who have only one autoimmune condition from those who have multiple.

Research Aims:

The hope is to discover biomarkers that can be used to identify individuals who are at risk of polyautoimmunity prior to their development. The team will then use these findings to develop a standardized approach to screen and care for patients with multiple autoimmune conditions.

Jocelyn Silvester, MD, Ph.D

Denis Chang, MD, MS

Children’s National Hospital Celiac Disease Program

Children’s National Hospital Celiac Disease Program

The Children’s National Celiac Disease Program and the Global Autoimmune Institute worked in partnership from 2015 to 2021 to develop robust educational resources, including:

• The gluten-free podcast and digital app streamlines access to information and navigating new lifestyle choices.
• Web-based video education seminars to help families with this autoimmune disease cope with the chronic condition.
• Building alliances with pediatric celiac disease programs across the United States to develop national recommendations for managing celiac disease at school and other learning environments.
• A research publication that aimed to investigate whether attention and executive functioning were associated with dietary adherence in children with celiac disease

In addition, through the synthesis of our financial support and the passionate dedication of both the Celiac Group at Children’s National Hospital and GAI, CNH established the first-of-its-kind multidisciplinary clinic for celiac disease patients.

The clinic brings together several medical specialties, including gastroenterology, neurology, psychology, nutrition, and education. These specialties collaborate to thoroughly diagnose and treat coexisting autoimmune diseases and neurological and psychological disorders, as well as to teach the patients and their families about proper nutrition and the many important aspects of living a gluten-free life.

Antibodies to an Epstein Barr Virus Protein that Cross-React with dsDNA Have Pathogenic Potential

Principal Investigator: Dr. Linda Spatz

Photo: Linda Spatz, PhD, and colleagues in their lab, City University of New York (CUNY)

This scientific investigation of patients with systemic lupus erythematosus (SLE) patients focuses on whether the Epstein-Barr Virus (EBV) causes the production of human antibodies using molecular mimicry in SLE patients. This could suggest that EBV may be a cause of SLE. The long-term goal of the study is to design a treatment to block certain EBV antibodies that cause organ damage in SLE patients.

You can find the research article, published in Molecular Immunology, here!

Exploring Effects of Cancer Immunotherapy Drugs on Autoimmune Manifestations

Principal Investigator: Dr. Paulina Chalan

Photo from left to right; Patrizio Caturegli, M.D., M.P.H., Director of The Autoimmune Research Center, Johns Hopkins Medicine; Sandra J. Boek, Executive Director, GAI; Paulina Chalan, PhD, Walter and Jean Boek Autoimmune Research Fellow, Division of Immunology, Johns Hopkins Medicine.

Postdoctoral research at Johns Hopkins Medicine is exploring the development of autoimmune hypophysitis (primarily affecting the pituitary gland) following cancer immunotherapy. This study is significant and unique, in that it will track the development of this autoimmune disease from inception, in mouse models, in order to better understand the evolution of the disease.