Selected extracts from Dr Rose’s homework papers on CD4-T cells, IgG4 and the other IgG’s
Jessica posted an excellent piece that presents expert initial analysis of IgG4 and other IgG’s here:
(100) IgG4, CD4s and why the LNP/mRNA platform should be prohibited (substack.com)
“Immunological shift to tolerance and reliance on/persistent activation of CD4+ T cells”
Before beginning I wil just pop this here for the sake of interest:
Thymus Gland: What It Is and How It Works (verywellhealth.com)
“Playing a role in immunity, autoimmunity, and aging” - maybe gorillas beat their chests for a reason!
Now, keeping in mind that my expertise in this field is barely above absolute zero, I post below extracts from two of the three homework papers linked at the top of Jessica’s article.
Although the first paper is no less significant than the others, I found it hard to extract details in a coherent way, so the extracts below are from the second and third homeworks – probably means I get a maximum of a B- !!
It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses.
IgG4-RD includes a “wide variety of diseases, formerly diagnosed as Mikulicz’s disease (MD) [66], autoimmune pancreatitis (AIP) [67], Riedel thyroiditis [68], interstitial pneumonitis [69,70], interstitial nephritis [71,72], prostatitis, lymphadenopathy [73,74], retroperitoneal fibrosis (RPF) [75,76], and inflammatory aortic aneurysm [77]”. It also plays a significant role in the pathogenesis of at least 13 autoimmune disorders. It has been shown that laboratory animals passively infused with human total IgG or IgG4 develop signs in 5 of these 13 disorders, proving the pathogenicity of this antibody.
IgG4-induced autoimmunity is suggested by the finding that the majority of antigen-specific autoantibodies are of the IgG4 class and that their concentrations correlate with the seriousness of the sickness for the eight remaining disorders [46]
Most crucially, new reports show that certain cancer patients receiving anti-PD-1 monoclonal antibody treatment have rapid disease progression (also known as hyper progressive disease (HPD) instead of cancer remission [93,94,95]. Notably, the PD-1 antibody belongs to the IgG4 family.
Most crucially, new reports show that certain cancer patients receiving anti-PD-1 monoclonal antibody treatment have rapid disease progression (also known as hyper progressive disease (HPD) instead of cancer remission [93,94,95]. Notably, the PD-1 antibody belongs to the IgG4 family.
An extensive review of the literature showed that mRNA vaccines are not the only ones that induce IgG4 antibody production. The HIV, Malaria, and Pertussis vaccines also elicited such a response. Overall, there are three critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration, repeated vaccination, and the type of vaccine used.
Compared to BNT162b2, the mRNA-1273 vaccine had a greater capability for inducing a prolonged IgG4 response. The amount and duration of the spike protein produced are presumably affected by the higher mRNA concentrations in the mRNA-1273 vaccine (100 µg) compared to the BNT162b2 vaccine (30 µg).
The increase in IgG4 levels after the third immunization with the Pfizer vaccine could reflect a tolerance mechanism that could prevent immune over-reactivity (cytokine storm) and progression to a critical stage [30]. However, this exacerbated immune reaction does not occur in young and healthy people, and it has been documented only in older patients with genetic susceptibility and those with comorbidities [129].
the immune system “learns” to tolerate a foreign, although innocuous, antigen. However, a very different situation occurs when a virus invades our body. In this scenario, vaccine-induced tolerance can potentially have several negative, unintended consequences because tolerance to the spike protein could inhibit the immune system from detecting and attacking the pathogen (Figure 4); thus, potentially exacerbating SARS-CoV2 pathology in susceptible individuals who suffer re-infection of COVID-19 in the setting of vaccine-induced immune suppression.
A study by Gazit et al. found that when the initial event (infection or vaccination) happened during January and February of 2021, SARS-CoV-2-naive vaccinees exhibited a 13.06-fold (95% confidence interval (CI), 8.08–21.11) greater risk for breakthrough infection with the Delta variant compared to the unvaccinated-previously-infected persons
There is now compelling evidence that, among COVID-19 vaccines, only the mRNA vaccines (but not the adenoviral vector-based vaccine from AstraZeneca) induced a remarkable increase in IgG4 levels, and such an increase was detected in SARS-CoV-2 uninfected individuals who received mRNA vaccinations before becoming infected with the virus, whereas for patients who had a previous infection before vaccination, IgG4 levels did not rise [31].
The HIV [113] and malaria trials [115], and studies with the Pertussis vaccine informed us that repeated vaccination was linked to reduced protection from infection, and this poor response was directly related to a higher IgG4 production.
Individuals with genetic susceptibility, immune deficiencies, and comorbidities are probably the most likely to be affected. However, this gives rise to a disturbing paradox—if people who are the most affected by the COVID-19 disease (the elderly, diabetics, hypertensive, and immunocompromised people like those with HIV) are also more susceptible to suffering the negative effects of repeated mRNA vaccination, is it then justified to booster them?
Severe COVID-19, for instance, has been associated with higher serum concentration of pro-inflammatory spike-specific IgG3 and afucosylated IgG1 antibodies capable of triggering exagger[1]ated macrophage activation [2-4].
On the other hand, anti-spike monoclonal neutralizing antibodies of IgG1 sub[1]class from the plasma of convalescent COVID-19 patients have been shown to prevent life-threatening disease and are currently under evaluation in clinical trials [5].
C-reactive protein (CRP), interleukin (IL)-6 serum IgG4 level, IgG4/ IgG ratio, and IgG4/IgG1 ratio were significantly higher in non[1]survivors, while the PaO2/FiO2 ratio was significantly lower in survivors.
Specifically, a concentration of serum IgG4 > 700 mg/dl and an IgG4/IgG1 ratio > 0.05 were associated with a significantly increased mortality at 30-days
Onwards
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