Vaccines and IgG4 do not induce or cause cancer.

Background information and context

When the immune system faces a threat, such as an infection, it produces antibodies to fight back. There are different types of antibodies, one type called IgG4. While it helps regulate inflammation, high levels of IgG4 are also linked to a rare condition called IgG4-related disease (IgG4-RD), which causes swelling and tissue damage in organs like the pancreas. But recent research reveals that IgG4 levels can also rise in certain cancers, especially pancreatic cancer. Here’s what we know and why scientists think IgG4 is a consequence of cancer, not a cause.

IgG4’s Role: Protector

IgG4 antibodies normally act as “peacekeepers,” calming overactive immune responses. In IgG4-RD, however, they misfire, attacking healthy tissues and mimicking diseases like pancreatitis or cancer. This overlap complicates diagnoses, as both pancreatic cancer and IgG4-RD can cause similar symptoms, such as jaundice or abdominal pain.

But crucially, studies show that pancreatic cancer itself can trigger a surge in IgG4. For example:

• A study by Shiokawa et al. (2015) found that elevated IgG4 levels occur in approximately 10–30% of pancreatic cancer patients, compared to just 1–2% of healthy adults.

• Research by Detlefsen et al. (2017) observed that IgG4 levels often drop after surgical removal of pancreatic tumors, suggesting the cancer itself was driving the increase.

• Higher IgG4 levels correlate with poor diagnosis.

Pancreatic Cancer: The Catalyst for IgG4 Production

Why would cancer cause IgG4 to spike? Scientists have two key explanations:

1. The Tumor’s “Immune Evasion” Strategy
   Cancer cells manipulate the immune system. Pancreatic tumours promote IgG4 production, which has anti-inflammatory properties. This could help tumours evade detection by immune cells that would otherwise attack them.

They also do this by recruiting and even inducing regulatory T cells (Treg), a T cell subset that reduces immune activity. In addition, tumours induce the expression of many other feedback mechanism molecules, such as checkpoint inhibitors PD-1, TIM-3 and LAG-3.

2. A Localized Immune Response
   IgG4-producing cells cluster around pancreatic tumours and nearby lymph nodes; not healthy tissue. Hart et al. suggest this reflects a targeted immune reaction to cancer, rather than the systemic attack seen in IgG4-RD.

https://journals.lww.com/pancreasjournal/abstract/2014/04000/risk_of_cancer_in_autoimmune_pancreatitis__a.14.aspx

https://www.sciencedirect.com/science/article/pii/S089339522203486X

https://link.springer.com/article/10.1007/s13317-015-0069-3

Why IgG4 Isn’t the Villain Here

Although there were early theories based on correlation, there’s no evidence that IgG4 causes cancer. Key findings highlight this:

• No Increased Cancer Risk in IgG4-RD Patients: Large-scale reviews show no significant rise in pancreatic cancer rates among IgG4-RD patients.

• IgG4 Levels Reflect Disease Activity: In cancer patients, IgG4 levels often correlate with tumor size or spread.

• Animal Studies Show No Tumor Growth from IgG4: Experiments confirm IgG4 alone doesn’t trigger cancer development.

Clues for Better Diagnosis

This relationship has real-world implications:

• A patient with a pancreatic mass and high IgG4 might be misdiagnosed with IgG4-RD and given steroids, delaying cancer treatment.

• Testing for cancer-specific markers (like CA19-9) alongside IgG4 can help doctors tell these conditions apart.

Key Takeaway

While IgG4 is a valuable red flag for immune disorders, its role in cancer is more like a smoke detector: it signals a problem (the tumour) but isn’t the fire itself. For pancreatic cancer, the surge in IgG4 appears to be the immune system’s reaction to the disease or even a trick the tumour uses to survive. By understanding this, doctors can better interpret test results and tailor treatments, giving patients the best chance at recovery.

Now, what about this panic-inducing preprint spreading vaccine disinformation?

First, it’s important to note: this is a preprint, meaning it has not undergone peer review. And frankly, it shows. The authors attempt to argue that COVID-19 vaccination increases levels of IgG4, that IgG4 is elevated in pancreatic cancer (PC), and that higher IgG4 correlates with worse outcomes. From this, they make the leap: COVID-19 vaccines cause or worsen pancreatic cancer.

But this link is fundamentally flawed. The association between elevated IgG4 and pancreatic cancer was well established long before COVID-19 vaccines existed. IgG4 levels have always been correlated with certain types of pancreatic cancer and with poorer prognoses. Unless the authors are suggesting the vaccines can time travel, this is a dead-end.