Next weekend Dysautonomia International will launch one of the most in-depth immunological studies in POTS to date during our 7th Annual Conference in Philadelphia! Titled “Immune-Phenotyping in Postural Orthostatic Tachycardia Syndrome,” the study takes a deep dive into possible immune mechanisms in POTS. You can support this important research by making a contribution to our POTS Research Fund at CurePOTS.org.

We’ve put together some FAQs about this year’s study.

Who is running this year’s study?

After helping researchers from Vanderbilt University, Mayo Clinic, UT Southwestern and other universities organize the annual Dysautonomia International Conference research study for the past five years, Dysautonomia International founder and President, Lauren Stiles, will lead this year’s study. Lauren was recruited to serve as a Research Assistant Professor of Neurology at Stony Brook University’s School of Medicine last year to help the university expand its autonomic disorders research, education and clinical care. She will be joined by co-investigators from Sweden, Dr. Jonas Axelsson, Medical Director of the Center for Apheresis and Stem Cell Handling at the Karolinska Institutet Hospital, and Dr. Artur Fedorowski, Senior Consultant for the Department of Cardiology and Head of the Syncope Unit at Skåne University Hospital. Drs. Axellson and Fedorowski have teamed up on several prior POTS studies that found interesting immunological results, and they have set up the leading POTS research program in Europe. The study team also includes incredible young researchers from Penn State Hershey, Rush University, University of Calgary, and Columbia University who are forging a career in medicine and academic research after their own experiences with POTS.

What are they studying?

During the conference, the research team will screen 100 POTS patient volunteers for the following:

HLA genetic markers: these are genetic markers that regulate the immune system;

these are genetic markers that regulate the immune system; immune cell phenotyping: B-cells, T-cells and NK-cells from collected peripheral blood mononuclear cells will be assayed with flow-cytometry with labelling according to the Freiburg (CD19, CD21, CD27, IgM, and IgD), FITMAN (CD45, CD4, CD8, CD45RA, CD27, CD69 and HLA-DR) or NK-panel (CD16, CD45 and CD56,), respectively;



B-cells, T-cells and NK-cells from collected peripheral blood mononuclear cells will be assayed with flow-cytometry with labelling according to the Freiburg (CD19, CD21, CD27, IgM, and IgD), FITMAN (CD45, CD4, CD8, CD45RA, CD27, CD69 and HLA-DR) or NK-panel (CD16, CD45 and CD56,), respectively; whole-tissue reactivity analysis: serum will be assessed for potential reactivity in routine clinical immunofluorescence assays for neuronal, pemphigoid and adrenal gland antibodies;

serum will be assessed for potential reactivity in routine clinical immunofluorescence assays for neuronal, pemphigoid and adrenal gland antibodies; novel calcium-mobilization assay: s erum samples will also be tested using a novel, proprietary ELISA assay to quantify the amount of IgG reactive to calcium-binding protein;

erum samples will also be tested using a novel, proprietary ELISA assay to quantify the amount of IgG reactive to calcium-binding protein; antibodies & immune markers associated with Sjögren’s syndrome : nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, PM-Scl, Jo-1, centromere protein B, PCNA, dsDNA, nucleosomes, histones, ribosomal P-proteins, AMA and M2;

nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, PM-Scl, Jo-1, centromere protein B, PCNA, dsDNA, nucleosomes, histones, ribosomal P-proteins, AMA and M2; antibodies associated with autoimmune encephalitis: NMDAR, AMPAR, GABAR, LGI1, CASPR2;

NMDAR, AMPAR, GABAR, LGI1, CASPR2; antibodies associated with neuromyelitis optica: NMO, AQP4;

NMO, AQP4; antibodies associated with polyneuropathy: GM, GM1, GM2, GM3, GD1b, GQ1b;

GM, GM1, GM2, GM3, GD1b, GQ1b; antibodies associated with myasthenia gravis: muscle AChR; and,

muscle AChR; and, urine screening for albuminuria, hematuria, leukocyturia, nitrate, sodium, potassium, magnesium, chloride, creatinine, urea and pH.

Thankfully, the researchers only need two tubes of blood and a small urine sample to run all of these tests. They will also conduct 10-minute bedside orthostatic vitals, a Beighton exam to screen for joint hypermobility, a medical history interview, and a survey to capture other information about the patient’s health and family history.

After the conference study is done, any remaining blood, serum and urine specimens will be stored in a biobank at the Karolinska Institutet for future studies analyzing other biomarkers of interest in POTS. Dysautonomia International has already been contacted by other researchers seeking access to this biobank material. Biobank specimens will be stored in a de-identified manner, meaning that the identify of the individual who provided the specimen remains anonymous. This is designed to protect patient privacy.

Why are the researchers studying these biomarkers?

Prior research suggests that a majority of people diagnosed with POTS have an autoimmune problem that may be causing or contributing to their symptoms. Almost every autoantibody that has been studied in POTS has been found in a higher percentage of POTS patients than it is found in the general population, but we really don’t know why that is and what other antibodies may be involved. The conference study is designed to dig a little deeper and search a little broader for immunological biomarkers in POTS, to get a bigger, and hopefully clearer, picture of what’s going on.

This review article provides a good summary of what has been found to date regarding autoimmunity in POTS, although even more research on autoimmunity in POTS has published since that review article came out in December 2018. There are two recent articles of note.

The first, a study finding that a subset of Korean POTS patients have HLA genetic markers highly associated with the development of autoimmune disease, also finding beta2 adrenergic receptor antibodies in these patients, and noting that two of these patients who received immunotherapy responded well to it. HLA markers can vary by race and ethnicity, so it’s important to search for these markers in other races and ethnicities to see if it’s a common finding amongst POTS patients of all backgrounds.

The second, a study from Dr. David Kem’s lab at the University of Oklahoma confirming a much higher rate of adrenergic receptor antibody activity in POTS patients compared to healthy people (the samples were collected during our 2014 Conference).

Inside scoop for our blog readers… we expect to see another important autoimmune POTS paper coming out in the next month or two.

How can I participate in the conference study?

Study enrollment will be open to the first 100 registered conference guests who volunteer to participate in the study and meet the enrollment criteria below. Please note, the conference is sold out and there are no volunteer or scholarship passes remaining. Study enrollment will begin at 6pm on Friday evening in the main hotel ballroom. The research team will be available to answer your questions and sign you up if you’re interested in participating. The actual study procedures will take place on Saturday and Sunday during the conference. Registered conference guests will receive an email this week with a detailed schedule.

Inclusion Criteria

· Individuals previously diagnosed with POTS by a physician

· Ages 12-80 years

· Male and female subjects are eligible

· Able and willing to provide informed consent (if ≥18 years) or assent with parental consent if age 12-17 years

Exclusion Criteria

· Inability to give, or withdrawal of, informed consent

· Use of immune modulating treatments within the prior 6 months

· Women who are or may be pregnant

· Other factors which in the investigator’s opinion would prevent the subject from completing the protocol

Study volunteers do not need to stop any of their medications, nor do they have to bring medical records to the conference. The study will be performed while the participants are dressed in their normal clothing, but the researchers will ask volunteers to remove any compression garments they wear before they arrive in the study room, because these garments can impact orthostatic vitals.

Will study participants get their lab results?

The researchers can share results from HLA marker and antibody analyses if study participants choose to receive them. However, they cannot provide clinical interpretation of any of the results.

When will the results of the study be publicly available?

The researchers will move as quickly as possible to complete the study and publish the results, but it can take more than a year to published a detailed research paper like this. We will share the eventual journal article through Dysautonomia International’s social media channels and email list as soon as it’s available.

How is this research being funded?

This research is being funded through Dysautonomia International’s POTS Research Fund as well as some grants from the Swedish government. You can support this work and other critically-needed POTS research by making a contribution at CurePOTS.org.

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