The Missing Piece in Understanding PANDAS and PANS?

What If Everything We Thought About PANDAS Was Wrong?

For years, scientists have debated how infections can trigger autoimmune diseases. The most widely accepted theory has been molecular mimicry, the idea that certain bacteria and viruses resemble human cells so closely that the immune system gets confused and attacks the wrong target.

But what if that’s not actually what’s happening?

A groundbreaking study from the Garvan Institute in Australia challenges this idea. Instead of simply tricking the immune system, infections appear to push it into overdrive, creating rogue immune cells that continue attacking long after the infection is gone.

This could change everything we thought we knew about PANDAS, a condition where children suddenly develop symptoms like OCD, tics, anxiety, severe mood disturbances, and urinary frequency after a streptococcal infection. If rogue B cells are involved, then PANDAS may not be an autoimmune condition at all. It may be an immune system that has lost control and won’t switch off.

It also raises big questions about PANS, a condition with similar symptoms triggered by a wider range of infections. If both conditions involve immune responses that spiral out of control, we may need to rethink how they are treated.

 

The Immune System as a Training Camp

B cells are like soldiers trained to fight infections. Normally, once the battle is won, most are dismissed, leaving behind a small, well-prepared reserve.

But what if the training never stops?

Instead of standing down, the immune system keeps pushing B cells through unnecessary training rounds. Some mutate into rogue fighters, attacking not just infections but the body itself.

This isn’t confusion. The immune system isn’t mistaking the body for strep. It is creating a new kind of attacker, one that no longer needs strep to keep causing harm.

This may explain why some children respond to treatments like IVIG and rituximab, which attempt to reset the immune response. IVIG floods the body with donor antibodies, helping to regulate immune activity and reduce inflammation. Rituximab goes even further, wiping out B cells entirely to eliminate the rogue ones.

These treatments can be effective, but they don’t always provide lasting relief. If the immune system remains stuck in this cycle, new rogue B cells may continue to emerge, which could explain why some children relapse even after initially responding to therapy.

 

What the Study Found and Why It Matters

The Garvan Institute study looked at patients with hepatitis C who developed cryoglobulinemic vasculitis, a condition where rogue B cells produce harmful autoantibodies. Researchers found:

B cell clones persisted even after the virus was eliminated

These clones had accumulated thousands of mutations, making them more aggressive

Instead of targeting the virus, they adapted to attack human tissue

There was no evidence of molecular mimicry. The immune system wasn’t making a mistake. Instead, it had been pushed into a chronic state of activation, allowing rogue B cells to persist and cause ongoing damage.

While this study focused on hepatitis C, the parallels to PANDAS are striking. Could similar rogue B cell activity be driving immune dysfunction in children with sudden-onset neuropsychiatric symptoms? This is a critical question that needs further research.

Could the same thing be happening in PANDAS and PANS?

 

Another Perspective: Dr. Dritan Agalliu’s Research

While the Garvan study focuses on rogue B cells, another important theory comes from Dr. Dritan Agalliu at Columbia University. His research suggests that PANDAS symptoms stem from blood-brain barrier breakdown, allowing immune cells to infiltrate the brain and trigger neurological symptoms.

Dr. Agalliu’s findings show that:

Repeated strep infections recruit Th17 immune cells, which target the blood-brain barrier

These immune cells weaken the barrier, allowing antibodies and inflammation to enter the brain

This may trigger the sudden onset of OCD, tics, and anxiety seen in PANDAS

Rather than rogue B cells running wild, Agalliu’s work highlights how repeated infections may weaken the brain’s defences, making it vulnerable to immune attacks.

So which explanation is correct? It may not be one or the other. PANDAS could involve both mechanisms, or different children may experience different pathways to the same symptoms.

 

Why Do Some Children Develop PANDAS While Others Recover?

Not every child who gets strep develops PANDAS. So why does it happen to some but not others? The answer likely lies in genetics, immune function, and environmental stressors- factors that shape how the body responds to infections.

The Role of Genetics

Genetic susceptibility doesn’t cause PANDAS or PANS outright, but it may determine how the immune system responds to infections. Some children inherit a tendency for prolonged immune activation, making them more vulnerable when faced with stressors like gut dysbiosis, chronic inflammation, or toxin exposure.

Some children are more vulnerable to prolonged immune activation. While a family history of autoimmunity can play a role, it isn’t the only factor. Variations in immune-related genes can influence how aggressively the body responds to infections and how efficiently it switches off inflammation.

For some, the immune system stays activated long after the infection is gone. Others have weaker immune tolerance, making them more prone to persistent inflammation. Instead of responding appropriately and then returning to a balanced state, their immune system remains on high alert.

 The Role of the Environment

Environmental stressors play a major role in shaping immune function and can push a vulnerable system into crisis.

Repeated antibiotic use disrupts gut bacteria, weakening immune regulation

Toxin exposure from mould or heavy metals keeps the immune system in a reactive state

Chronic stress raises inflammation and impairs immune resilience

Gut imbalances contribute to a leaky gut, allowing inflammatory triggers to persist

For some children, a strep infection isn’t the root cause of PANDAS, it is the final stressor that tips an already primed immune system into dysfunction.

 

Can We Stop Rogue B Cells in Their Tracks?

If chronic immune activation is the real issue, then simply clearing infections isn’t enough. If antibiotics were the solution, one course would be enough to fix PANDAS. Yet that’s not what we see.

While short-term antibiotics can help clear an active strep infection, they don’t address the underlying immune dysregulation that keeps children stuck in a cycle of relapse. Some antibiotics, particularly macrolides like azithromycin and clarithromycin, as well as tetracyclines like minocycline, have additional immunomodulatory effects. They can temporarily reduce inflammation and suppress excessive immune activation, but they do not resolve the core dysfunction driving PANDAS. This is why so many families find themselves trapped in years of antibiotic use without lasting improvement.

In our clinic, we regularly meet children who have been on antibiotics for years, sometimes more than five years straight, yet they remain stuck in the same relentless cycle of flare-ups. Instead of resolving the problem, their immune system continues attacking as if it has forgotten how to switch off.

Microimmunotherapy: A Smarter Approach

Microimmunotherapy is designed to work with the immune system rather than against it. Unlike conventional immunotherapy, which often involves suppressing immune function, Microimmunotherapy delivers ultra-low doses of immune messengers to ‘train’ the immune system to regulate itself more effectively.

Unlike IVIG or rituximab, which either flood the body with antibodies or eliminate B cells entirely, Microimmunotherapy works in a far more targeted way. Using ultra-low doses of immune messengers, this approach gently modulates immune activity, restoring balance without shutting down essential immune functions.

At Brainstorm Health, we have been incorporating Microimmunotherapy into our clinical approach for nearly five years. We have observed improvements in children with PANDAS, PANS, and other immune-related conditions, particularly in cases where immune activation remains persistent.

Microimmunotherapy helps to:


Regulate chronic immune activation without suppressing protective responses

Reduce inflammation while maintaining immune function

Prevent new rogue B cells from forming

Rather than wiping out immune cells, Microimmunotherapy restores balance, teaching the immune system when to fight and when to stand down.

The Bigger Picture: Rethinking PANDAS and PANS

It’s possible that PANDAS and PANS aren’t autoimmune conditions at all or at least not in the way we’ve traditionally thought. Rather than a case of mistaken identity where the immune system confuses the brain for an infection, it could be that the immune system simply doesn’t know when to switch off.

And that changes everything. Antibiotics, IVIG, and rituximab can sometimes interrupt the immune response, offering relief, but they don’t always tackle the underlying issue. What we need are smarter approaches that restore immune balance rather than just pressing pause on the attack. That’s where Microimmunotherapy comes in.

This isn’t just about managing symptoms, it’s about changing the trajectory of a child’s life. The next step is to ensure more research focuses on immune regulation in PANDAS and PANS. Parents and practitioners need better options, and this new understanding of immune dysfunction may be the key to long-term solutions.

For the first time, we have a clearer path forward. And if I were a parent facing this, I would want to know about it.

 

Full Transparency Statement

To ensure full transparency, we want to make it clear that we have undertaken extensive training in Microimmunotherapy (MIT), all of which has been personally funded. We have no financial ties to any MIT products or therapies and receive no compensation for recommending them.

Our approach is entirely focused on what is most effective for the children and families we support, free from any commercial influence. Our priority is always the best possible outcomes, guided by clinical experience and emerging research.

 

IMPORTANT

The information provided in this article is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. It is crucial to consult with medical doctors or qualified functional medicine practitioners to address specific health concerns and obtain personalised guidance tailored to individual needs. Never add any supplements to your plan until it has been assessed and approved by your medical doctor or a suitable qualified practitioner who is familiar with your health history. 

Concerned about your child’s health? We’d love to have a chat with you. 

Click the link here to book your Free Discovery Call.

 

Reference 

Young, C., Singh, M., Jackson, K.J.L., Bull, R.A., Suan, D., and Goodnow, C.C. (2024) ‘A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease’, Immunity, [online] Available at: https://www.cell.com/immunity/fulltext/S1074-7613(24)00575-2

Dileepan, T., Linehan, J.L., Moon, J.J., Pepper, M., Jenkins, M.K., Cleary, P.P., and Agalliu, D. (2016) ‘Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells’, Journal of Clinical Investigation, 126(1), pp. 303–317. Available at: https://www.jci.org/articles/view/80792

Wayne, C.R., Bremner, L., Faust, T.E., Durán-Laforet, V., Ampatey, N., Ho, S.J., Feinberg, P.A., Arvanitis, P., Ciric, B., Delaney, S.L., Vargas-Deming, W., Swedo, S., Menon, V., Schafer, D.P., Cutforth, T., and Agalliu, D. (2023) ‘Distinct Th17 effector cytokines differentially promote microglial and blood-brain barrier inflammatory responses during post-infectious encephalitis’, bioRxiv, [online] Available at: https://doi.org/10.1101/2023.03.10.532135