We article explores downstream immune implications of increased IgG4 after COVID vaccination
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant
Elevated SARS-CoV-2–specific IgG4 titers decrease ADCC but can increase ADCP when spike-specific antibody titers are low.
www.science.org
March 1, 2025 at 2:14 AM
We article explores downstream immune implications of increased IgG4 after COVID vaccination
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
We've already seen remarkable results for lupus and other autoimmune diseases with CD19 B cell depletion therapy. Now add IgG4 related disease (which has no treatment) in a new randomized trial
nejm.org/doi/full/10....
nejm.org/doi/full/10....
Inebilizumab for Treatment of IgG4-Related Disease | NEJM
IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated
disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells
and may be effective for treat...
nejm.org
November 14, 2024 at 3:15 PM
We've already seen remarkable results for lupus and other autoimmune diseases with CD19 B cell depletion therapy. Now add IgG4 related disease (which has no treatment) in a new randomized trial
nejm.org/doi/full/10....
nejm.org/doi/full/10....
#immunosky #IDsky #medsky 🧪
I know everyone missed thinking about IgG4, but we have a new study that finds some very interesting properties of anti-spike IgG4 elicited by mRNA vaccines
tl;dr- IgG4 seems to buffer inflammation but enhances the function of other antibodies when titers are lower
🧵
I know everyone missed thinking about IgG4, but we have a new study that finds some very interesting properties of anti-spike IgG4 elicited by mRNA vaccines
tl;dr- IgG4 seems to buffer inflammation but enhances the function of other antibodies when titers are lower
🧵
Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant
Elevated SARS-CoV-2–specific IgG4 titers decrease ADCC but can increase ADCP when spike-specific antibody titers are low.
www.science.org
March 1, 2025 at 4:55 AM
#immunosky #IDsky #medsky 🧪
I know everyone missed thinking about IgG4, but we have a new study that finds some very interesting properties of anti-spike IgG4 elicited by mRNA vaccines
tl;dr- IgG4 seems to buffer inflammation but enhances the function of other antibodies when titers are lower
🧵
I know everyone missed thinking about IgG4, but we have a new study that finds some very interesting properties of anti-spike IgG4 elicited by mRNA vaccines
tl;dr- IgG4 seems to buffer inflammation but enhances the function of other antibodies when titers are lower
🧵
Why IgG4 Isn’t the Villain Here
Although there were early theories based on correlation, there’s no evidence that IgG4 causes cancer.
Although there were early theories based on correlation, there’s no evidence that IgG4 causes cancer.
Oh dear, antivax scaremongers are trying to generate panic and more antivax sentiment with another bad study.
First note this is a pre-print, no expert has looked at it yet, and that shows. 🚩🚩
Yet, anti-vaxxers are already abusing it.
1/8
First note this is a pre-print, no expert has looked at it yet, and that shows. 🚩🚩
Yet, anti-vaxxers are already abusing it.
1/8
April 17, 2025 at 9:52 AM
Why IgG4 Isn’t the Villain Here
Although there were early theories based on correlation, there’s no evidence that IgG4 causes cancer.
Although there were early theories based on correlation, there’s no evidence that IgG4 causes cancer.
#Medsky🧪 #IDsky #immunosky #publichealth The NVX-CoV2373 recombinant protein-based vaccine ( #Novavax) doesn't seem to induce significant IgG4 increases or impair Fcγ-dependent effector responses like those seen with mRNA vaccines, even after multiple exposures.
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
July 26, 2025 at 11:13 AM
#Medsky🧪 #IDsky #immunosky #publichealth The NVX-CoV2373 recombinant protein-based vaccine ( #Novavax) doesn't seem to induce significant IgG4 increases or impair Fcγ-dependent effector responses like those seen with mRNA vaccines, even after multiple exposures.
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
For patients with IgG4-related disease, there are no approved therapies. Research findings on the efficacy and safety of inebilizumab ― a monoclonal antibody that targets and depletes CD19+ B-cells ― are summarized in a new Quick Take video. nej.md/421enZX
#MedSky #RheumSky
#MedSky #RheumSky
Inebilizumab for IgG4-Related Disease | NEJM
Quick Take Video Summary from The New England Journal of Medicine — Inebilizumab for IgG4-Related Disease
nej.md
March 30, 2025 at 1:09 PM
For patients with IgG4-related disease, there are no approved therapies. Research findings on the efficacy and safety of inebilizumab ― a monoclonal antibody that targets and depletes CD19+ B-cells ― are summarized in a new Quick Take video. nej.md/421enZX
#MedSky #RheumSky
#MedSky #RheumSky
Interestingly, patients with known IgG4-related disease (IgG4-RD) do not show elevated Spike-specific IgG4, demonstrating that vaccination does not exacerbate IgG4-RD or drive IgG4 production in a disease-specific way.
7/8
7/8
April 16, 2025 at 9:21 PM
Interestingly, patients with known IgG4-related disease (IgG4-RD) do not show elevated Spike-specific IgG4, demonstrating that vaccination does not exacerbate IgG4-RD or drive IgG4 production in a disease-specific way.
7/8
7/8
8️⃣ Ergänzend dazu: Mechanismen des IgG4-Klassenwechsels
Ein weiteres Paper zeigt, dass wiederholte mRNA-Impfungen zu einer verstärkten IgG4-Dominanz führen, während proteinbasierte Impfstoffe wie Novavax eine stabile IgG1/IgG3-Antwort bewahren.
👉 Warum ist das entscheidend? 👇
Ein weiteres Paper zeigt, dass wiederholte mRNA-Impfungen zu einer verstärkten IgG4-Dominanz führen, während proteinbasierte Impfstoffe wie Novavax eine stabile IgG1/IgG3-Antwort bewahren.
👉 Warum ist das entscheidend? 👇
February 1, 2025 at 3:18 AM
8️⃣ Ergänzend dazu: Mechanismen des IgG4-Klassenwechsels
Ein weiteres Paper zeigt, dass wiederholte mRNA-Impfungen zu einer verstärkten IgG4-Dominanz führen, während proteinbasierte Impfstoffe wie Novavax eine stabile IgG1/IgG3-Antwort bewahren.
👉 Warum ist das entscheidend? 👇
Ein weiteres Paper zeigt, dass wiederholte mRNA-Impfungen zu einer verstärkten IgG4-Dominanz führen, während proteinbasierte Impfstoffe wie Novavax eine stabile IgG1/IgG3-Antwort bewahren.
👉 Warum ist das entscheidend? 👇
*watching a 3 hour conference video on IgG4-related diseases* wow i’m gonna start diagnosing everyone with IgG4-related disease!
*watching a 3 hour conference video on vasculitides* wow i’m gonna start diagnosing everyone with vasculitides!
*watching a 3 hour conference video on tubulointerstitia-
*watching a 3 hour conference video on vasculitides* wow i’m gonna start diagnosing everyone with vasculitides!
*watching a 3 hour conference video on tubulointerstitia-
June 4, 2026 at 3:52 AM
*watching a 3 hour conference video on IgG4-related diseases* wow i’m gonna start diagnosing everyone with IgG4-related disease!
*watching a 3 hour conference video on vasculitides* wow i’m gonna start diagnosing everyone with vasculitides!
*watching a 3 hour conference video on tubulointerstitia-
*watching a 3 hour conference video on vasculitides* wow i’m gonna start diagnosing everyone with vasculitides!
*watching a 3 hour conference video on tubulointerstitia-
Seeking a mechanistic explanation, the authors focus on total IgG4, initially regardless of its specificity. This is misleading: pancreatic cancer itself is known to stimulate IgG4 production. Even with a relatively large sample, the difference in IgG4 levels between groups is modest.
5/8
5/8
April 16, 2025 at 9:21 PM
Seeking a mechanistic explanation, the authors focus on total IgG4, initially regardless of its specificity. This is misleading: pancreatic cancer itself is known to stimulate IgG4 production. Even with a relatively large sample, the difference in IgG4 levels between groups is modest.
5/8
5/8
9️⃣ IgG4 & Immuntoleranz
• IgG4 entsteht bei chron. Antigen-Exposition oder Toleranz-Entwicklung (z. B. bei Allergie-Therapien).
• Bei wiederholter mRNA-Impfung tritt eine Reduktion der Fc-Effektorfunktionen (ADCC, ADCP) ein
• Das verändert die langfristige Schutzwirkung (9/x)
• IgG4 entsteht bei chron. Antigen-Exposition oder Toleranz-Entwicklung (z. B. bei Allergie-Therapien).
• Bei wiederholter mRNA-Impfung tritt eine Reduktion der Fc-Effektorfunktionen (ADCC, ADCP) ein
• Das verändert die langfristige Schutzwirkung (9/x)
February 1, 2025 at 3:18 AM
9️⃣ IgG4 & Immuntoleranz
• IgG4 entsteht bei chron. Antigen-Exposition oder Toleranz-Entwicklung (z. B. bei Allergie-Therapien).
• Bei wiederholter mRNA-Impfung tritt eine Reduktion der Fc-Effektorfunktionen (ADCC, ADCP) ein
• Das verändert die langfristige Schutzwirkung (9/x)
• IgG4 entsteht bei chron. Antigen-Exposition oder Toleranz-Entwicklung (z. B. bei Allergie-Therapien).
• Bei wiederholter mRNA-Impfung tritt eine Reduktion der Fc-Effektorfunktionen (ADCC, ADCP) ein
• Das verändert die langfristige Schutzwirkung (9/x)
A Case of IgG4-Related Disease Potentially Triggered by COVID-19 Vaccination: Longitudinal Serum IgG4 Monitoring from Prevaccination
Causality of IgG4 and disease? No
Any evidence for it? No
academic.oup.com/mrc...
1/5
Causality of IgG4 and disease? No
Any evidence for it? No
academic.oup.com/mrc...
1/5
A Case of IgG4-Related Disease Potentially Triggered by COVID-19 Vaccination: Longitudinal Serum IgG4 Monitoring from Prevaccination
Abstract. We report a case of a 64-year-old Japanese man who developed IgG4-related pericoronary arteritis following mRNA-based COVID-19 vaccination. The p
academic.oup.com
July 27, 2025 at 6:42 PM
A Case of IgG4-Related Disease Potentially Triggered by COVID-19 Vaccination: Longitudinal Serum IgG4 Monitoring from Prevaccination
Causality of IgG4 and disease? No
Any evidence for it? No
academic.oup.com/mrc...
1/5
Causality of IgG4 and disease? No
Any evidence for it? No
academic.oup.com/mrc...
1/5
For a detailed background and context with scientific references as well as discussion of the preprint, see my substack:
Vaccines and IgG4 do not induce or cause cancer.
marcveldhoen.substac...
8/8
Vaccines and IgG4 do not induce or cause cancer.
marcveldhoen.substac...
8/8
Vaccines and IgG4 do not induce or cause cancer.
Background information and context
marcveldhoen.substack.com
April 16, 2025 at 9:21 PM
For a detailed background and context with scientific references as well as discussion of the preprint, see my substack:
Vaccines and IgG4 do not induce or cause cancer.
marcveldhoen.substac...
8/8
Vaccines and IgG4 do not induce or cause cancer.
marcveldhoen.substac...
8/8
John Stone et al MITIGATE trial: CD19-targeted B-cell depletion with inebilizumab in IgG4-related disease
"Inebilizumab reduced the risk of treated and adjudicated IgG4-related disease flares by 87% as compared with placebo" 🧪⚕️#ImmunoSky
"Inebilizumab reduced the risk of treated and adjudicated IgG4-related disease flares by 87% as compared with placebo" 🧪⚕️#ImmunoSky
Inebilizumab for Treatment of IgG4-Related Disease | NEJM
IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated
disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells
and may be effective for treat...
www.nejm.org
December 3, 2024 at 3:24 PM
John Stone et al MITIGATE trial: CD19-targeted B-cell depletion with inebilizumab in IgG4-related disease
"Inebilizumab reduced the risk of treated and adjudicated IgG4-related disease flares by 87% as compared with placebo" 🧪⚕️#ImmunoSky
"Inebilizumab reduced the risk of treated and adjudicated IgG4-related disease flares by 87% as compared with placebo" 🧪⚕️#ImmunoSky
Animal Studies Show No Tumor Growth from IgG4: Experiments confirm IgG4 alone doesn’t trigger cancer. development.
April 17, 2025 at 9:52 AM
Animal Studies Show No Tumor Growth from IgG4: Experiments confirm IgG4 alone doesn’t trigger cancer. development.
There was also a lot of discussion about mRNA and IgG4 production, but I’m honestly uncertain how important this is.
x.com/ENirenberg/s...
5/
x.com/ENirenberg/s...
5/
x.com
August 22, 2025 at 6:34 PM
There was also a lot of discussion about mRNA and IgG4 production, but I’m honestly uncertain how important this is.
x.com/ENirenberg/s...
5/
x.com/ENirenberg/s...
5/
Excellent review of IgG4 disease and treatment in KIR
IgG4-Related Kidney Disease and IgG4-Related Retroperitoneal Fibrosis: An Update on Diagnosis and Treatment
Renal involvement of IgG4-related disease (IgG4-RD) disease, collectively termed IgG4-related kidney disease (IgG4-RKD), most commonly manifests as tubulointerstitial nephritis (TIN) but can also…
www.kireports.org
June 2, 2026 at 11:14 PM
Excellent review of IgG4 disease and treatment in KIR
Malone claims this is leading to an immunologic adverse event of "broad-based class switching." This is scientifically illiterate; I'm guessing he's referring to the class switching to IgG4, which is not an adverse event.
deplatformdisease.substack.com/p/igg4-covid...
www.science.org/doi/10.1126/...
deplatformdisease.substack.com/p/igg4-covid...
www.science.org/doi/10.1126/...
IgG4, COVID, and mRNA vaccines: Not so Tolerant
mRNA vaccines produce an unusually high fraction of IgG4 against spike. Some have falsely claimed this indicates tolerance developing against SARS-CoV-2. The truth of IgG4 is more complex.
deplatformdisease.substack.com
June 25, 2025 at 5:38 PM
Malone claims this is leading to an immunologic adverse event of "broad-based class switching." This is scientifically illiterate; I'm guessing he's referring to the class switching to IgG4, which is not an adverse event.
deplatformdisease.substack.com/p/igg4-covid...
www.science.org/doi/10.1126/...
deplatformdisease.substack.com/p/igg4-covid...
www.science.org/doi/10.1126/...
Perfect timing for @kireports.bsky.social to publish the IgG4 review as the @nejm.org publishes this RCT of Obexelimab
www.nejm.org/doi/full/10....
www.nejm.org/doi/full/10....
June 3, 2026 at 10:28 AM
Perfect timing for @kireports.bsky.social to publish the IgG4 review as the @nejm.org publishes this RCT of Obexelimab
www.nejm.org/doi/full/10....
www.nejm.org/doi/full/10....
Our online free tool helps you perform a classification of an IgG4-RD patient according to the 2019 ACR/EuLAR classification criteria for IgG4-RD (pmid.us/31796497).
Give it a try!
davte.it/IgG4-RD.html
(Courtesy of Dr Davide Testa)
#IgG4-RD #RheumSky
Give it a try!
davte.it/IgG4-RD.html
(Courtesy of Dr Davide Testa)
#IgG4-RD #RheumSky
The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease - PubMed
IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serological, radiological and pathological data is required for diagnosis. This work...
pmid.us
November 25, 2024 at 7:36 PM
Our online free tool helps you perform a classification of an IgG4-RD patient according to the 2019 ACR/EuLAR classification criteria for IgG4-RD (pmid.us/31796497).
Give it a try!
davte.it/IgG4-RD.html
(Courtesy of Dr Davide Testa)
#IgG4-RD #RheumSky
Give it a try!
davte.it/IgG4-RD.html
(Courtesy of Dr Davide Testa)
#IgG4-RD #RheumSky
Tokyo researchers studied 105 Long COVID patients and found that those whose immune systems shifted toward making more spike-specific IgG4 antibodies were nearly 4 times more likely to recover.
IgG4 class switching predicted clinical improvement.
www.journalofinfection.com/article/S016...
IgG4 class switching predicted clinical improvement.
www.journalofinfection.com/article/S016...
SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID
Letter to the Editor
www.journalofinfection.com
October 27, 2025 at 4:00 PM
Tokyo researchers studied 105 Long COVID patients and found that those whose immune systems shifted toward making more spike-specific IgG4 antibodies were nearly 4 times more likely to recover.
IgG4 class switching predicted clinical improvement.
www.journalofinfection.com/article/S016...
IgG4 class switching predicted clinical improvement.
www.journalofinfection.com/article/S016...
SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID
105 longcovid patients, small study. Association only.
www.journalofinfecti...
1/4
105 longcovid patients, small study. Association only.
www.journalofinfecti...
1/4
SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID
Letter to the Editor
www.journalofinfection.com
October 28, 2025 at 8:47 AM
SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID
105 longcovid patients, small study. Association only.
www.journalofinfecti...
1/4
105 longcovid patients, small study. Association only.
www.journalofinfecti...
1/4
7️⃣ mRNA-Impfstoffe verändern zusätzlich die Antikörperklasse – weitere Probleme
📌 Wiederholte mRNA-Booster → IgG4-Klassenwechsel.
📌 IgG4 ist kein antivirales Antikörperprofil, sondern tritt bei Toleranzreaktionen auf.
📌 Novavax bewahrt IgG1/IgG3-Antwort 8/x
📌 Wiederholte mRNA-Booster → IgG4-Klassenwechsel.
📌 IgG4 ist kein antivirales Antikörperprofil, sondern tritt bei Toleranzreaktionen auf.
📌 Novavax bewahrt IgG1/IgG3-Antwort 8/x
February 2, 2025 at 5:15 AM
7️⃣ mRNA-Impfstoffe verändern zusätzlich die Antikörperklasse – weitere Probleme
📌 Wiederholte mRNA-Booster → IgG4-Klassenwechsel.
📌 IgG4 ist kein antivirales Antikörperprofil, sondern tritt bei Toleranzreaktionen auf.
📌 Novavax bewahrt IgG1/IgG3-Antwort 8/x
📌 Wiederholte mRNA-Booster → IgG4-Klassenwechsel.
📌 IgG4 ist kein antivirales Antikörperprofil, sondern tritt bei Toleranzreaktionen auf.
📌 Novavax bewahrt IgG1/IgG3-Antwort 8/x