Autoimmune Disorders: Driving Forces, the Inflamed Brain, and Taking the High Road

IFM Director of Medical Education Dan Lukaczer, ND, IFMCP, spoke with Samuel Yanuck, DC, FACFN, FIAMA, to discuss inflammation, T-cell regulation, and compression of morbidity in relation to autoimmune disease. Dr. Yanuck is CEO and director of education for Cogence Immunology, a fully online functional immunology self-paced course for clinicians. He is also an adjunct assistant professor in the Department of Physical Medicine and Rehabilitation at the University of North Carolina School of Medicine. In the following interview, Dr. Yanuck shares his clinical insights on the importance of discovering drivers of disease, the role of inflammation and the regulation of T-cells, and the idea of “Taking the High Road” in the overall health of patients.

The following text provides a breakdown of the topics discussed in the interview, as well as Dr. Yanuck’s observations and insights.

Clinical Practice: Building a Map to Find the Driving Force

In his private practice, Dr. Yanuck primarily sees patients with immunological disorders and those who struggle with a range of autoimmune issues.

"The goal is to get their autoimmunity to be as dormant as possible."
– Dr. Yanuck

To achieve this goal, Dr. Yanuck builds a map of the patient’s case. Instead of a specific diagnostic label, he wants to understand “how that autoimmune process is occurring in the total context of the picture of the patient.”

Clinical example
Podcast Homepage

A patient presents with the chronic autoimmune neuromuscular disease myasthenia gravis, and Dr. Yanuck builds the map to find a potential driving force for the condition.

  • A previous extensive work-up from another medical facility missed an important detail
    • Patient has hereditary hemochromatosis.
  • Labs show elevated iron saturation levels.
  • MRI shows iron infiltration in the liver.
  • How does this affect the autoimmune disorder?
    • The iron levels activate a substantial oxidative inflammatory reaction.
  • Conclusion: The patient’s autoimmune condition is driven by another process not previously noticed.

Dr. Yanuck emphasizes the importance of embedding the diagnostic facts into the patient’s total picture in order to develop an intervention strategy that will “give the person advantages so that they have much better outcomes with their autoimmune disease.”

Neurological Inflammation

When Dr. Lukaczer asks what kinds of neuro-inflammatory processes Dr. Yanuck routinely looks for with his patients with autoimmune dysfunction, Dr. Yanuck responds, “There are two parts to that discussion.”

Microglial cells

Microglial cells are macrophages in the brain. For Dr. Yanuck, the question is, “How do the microglial cells know which neurons are the dead ones?”

The decision to eat neurons:

      • Based on chemical signaling exchanged between neurons and microglia.
        • Signals include TNF-alpha and interleukin-1 beta.

The issue with TNF-alpha and interleukin-1 beta:

      • Both chemicals participate in the inflammatory signaling system.

Dr. Yanuck suggests that if the brain is more inflamed and these chemical signals are active, their influence increases the likelihood that microglia will eat neurons adjacent to them, whether dead or alive.

"You don’t want an inflamed brain, because you’ll lose neurons over it."
– Dr. Yanuck
How DId the Brain Get Inflamed?

The next question posed by Dr. Yanuck is, “How does the brain get inflamed?” Besides a physical trauma, the likely answer to brain inflammation is that the body itself is inflamed.

  • Systemic inflammation drives neuroinflammation.
  • Clinical assessment and application:
    • Consider anything that promotes or generates systemic inflammation. Examples:
      • Dysbiosis – epithelial cells of the intestine generating inflammatory cytokines.
      • Insulin resistance – known to be inflammatory.
      • Chronic stress – inflammatory via systemic macrophage upregulation of NF-kappa B.

In conclusion, Dr. Yanuck notes that your dysbiosis, chronic stress, and insulin resistance is ultimately losing you neurons.

Markers of Overall Inflammation

  • C-reactive protein (CRP) is useful, but this and other lab markers may not be adequately sensitive.
    • Patients may be inflamed, but their CRP normal.
  • Patient history provides clues to the extent of their inflammation.
    • Monitoring such things as achy knees or brain fog to evaluate any alleviation of symptoms, or how far treatment has moved the needle.
New research and potential Lab marker

Complement component 1q (C1q) is a protein complex that is part of the innate immune system.

  • Complement C1q is involved in microglial cell activation.
  • Clinical applications are not entirely clear.
  • Research is intriguing, but inconsistent.
    • Protective example: C1q has protective roles in increasing microglial phagocytosis of amyloid protein.
    • Problematic example: C1q as an autocrine activator of microglial cells. Overactivation may lead to destruction of neurons.

Botanicals, TH17 Cells, and Autoimmunity

Dr. Yanuck shares his concern about black elderberry in relation to autoimmunity. Black elderberry is “great at knocking out colds, but it’s an IL-6 promoter, rather decisively, so it will stir up the TH17 cell activation.”

He explains that IL-6 signals naïve T-cells to become TH17 cells:

  • You start with a naïve T-cell.
  • Chemical signaling in the tissue will tell it what kind of T-cell to turn into.
  • If the chemical signaling is changed so that naïve T-cells become TH17 cells, now there’s promotion of autoimmune tissue destruction.

“Now you’re off to the races with your autoimmune activation,” says Dr. Yanuck.

Downregulation of TH17 cells

Dr. Yanuck suggests two strategies for the regulation of TH17 cells.

  • Promote regulatory T-cells.
    • Vitamin D, vitamin A, curcumin, resveratrol, sulforaphane, fish oil.
      • Related to inhibition of TH17 cells.
  • Promote Th1 cells.
    • Old research could not distinguish between TH17 and Th1 cells.
    • New research:
      • The Th1 cell has a different receptor than the TH17 cell.
      • Th1 cells inhibit TH17 cells.
    • Promote with berberine, ginger, sulforaphane, echinacea.

“Taking the High Road” in Overall Health for Patients

This perspective was inspired by the work of Dr. James Fries (Stanford University).

  • Squaring the survival curve
  • Compression of morbidity

Humans decline over their lifetimes, and Dr. Yanuck draws this concept out for his patients as a three-layer cake, with top, middle, and bottom bands.

  • Youth and quick recovery is in the top band.
  • Diseases such as cancer, diabetes, and heart disease are in the bottom band.
  • What is in the middle band?
    • Declines in function, potentially without any disease name.
    • Chronic ailments that affect quality of life but may not kill the patient:
      • Rheumatoid arthritis
      • Hashimoto’s thyroiditis
      • Type 2 diabetes
      • Migraines
      • Dysbiosis
    • Gives physicians a clue about how a patient is declining.

A clinician’s goal is to take patients in the middle band and push out their timeline so that the patients are well for a maximum length of time.

"You’re trying to kick the can down the road ahead of you so that you are well, then you’re well, then you’re well, then you’re well. Then finally, on one particular day, you pass away."
– Dr. Yanuck

The task from a Functional Medicine point of view:

  • Identify and evaluate symptoms people have as they decline.
  • Use that information as a way of understanding the map of the patient’s case.
  • Identify the effective clinical targets.

Subsequently, this allows accurate clinical interventions, with the goal that “all of their morbidity is compressed into that very, very, very end of life.”

Dr. Yanuck is one of the expert speakers at IFM’s 2020 Annual International Conference (AIC)


Related Insights