Vaccine Excipients and Spike Protein May Trigger Alopecia Areata

New Study Identifies Mechanisms of COVID-related Alopecia Areata

It’s clear that many different vaccines can potentially trigger alopecia areata. Vaccinations have previously been suggested as a possible trigger for immune-mediated alopecia, such as hepatitis B, herpes zoster, quadrivalent HPV, influenza, and Japanese encephalitis vaccines. COVID vaccines are now on these lists too.

It has been proposed that epitopes derived from the COVID19 virus or the COVID19 vaccine resemble antigen epitopes of the human and can trigger alopecia.

Wang et al 2023

In a new study, authors set out to better understand the potential mechanisms of COVID-19 vaccine-related alopecia areata (AA).

The authors recruited patients presenting with COVID-19 vaccine-related alopecia areata (AA) during the period 2021 to 2022. The authors compared their results to control patients who did not have alopecia areata from vaccinations.

There were 27 new-onset of vaccine related alopecia areata patients  and 106 vaccines-tolerant individuals. The mean age of the patients with vaccine-related AA was 38.2 while that of the tolerant controls was 43.7 years. Approximately 63.0% of the vaccine-related AA patients were women. There was no significant difference in sex and age between the groups.

Of the 27 patients with vaccine related AA, the Moderna vaccine (mRNA-1273 vaccine) was the culprit in 40.7% of patients. The Pfizer vaccine (BNT162b2 vaccine) was used in 29.6% of patients and Astrazeneca vaccine (AZD1222 vaccine) was used in 25.9% of patients. Other vaccines (such as the MVC-COV1901 vaccine) were used in 3.7%.

Most patients (59.6%) had symptoms occurring after the second dose of the vaccine. In 22.2 % of patients it was the very first dose that triggered alopecia areata and in 18.5 % symptoms occurred after the third and fourth doses of the vaccine.

Elevated Total IgG, Positive ANA and Elevated Eosinophils Associated with Vaccine AA

The authors found that there were three blood test results that were much more likely to be elevated in COVID – AA patients than controls. These included positive ANA, total IgE levels and eosinophilia. In this study, 20 % of COVID – AA patients had positive ANA compared to 3.8% of controls. (p=0.013). 45.5 % of COVID – AA patients had increased total IgE levels compared to 10.2 % of controls (p=0.00019). 28.6 % of COVID – AA patients had eosinophilia compared to 10.2 % of controls (p=0.027).

Serum CCL18 and Granulysin Associated with Vaccine AA

The authors assessed the serum levels of 23 different types of cytokines, chemokines, and inflammatory proteins. The patients with COVID-19 vaccines-related AA had significantly higher levels of PARC/CCL18 and granulysin  than controls.

For those not aware, CCL18 is produced by antigen presenting cells. It is involved in the innate and adaptive immune system and plays a role in attracting immune cells. Granulysin is a pro-inflammatory molecule expressed by NK cells and activated T cells.  

Lymphocyte Activation Tests Point to Role Excipients and Spike Protein

Some of the key experiments done by the authors were the lymphocyte activation tests.

The authors showed using an in vitro lymphocyte activation test (LAT) that granulysin, granzyme B, and IFN-γ released from the T cells of COVID-19 vaccines-related AA patients could be significantly increased by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P = 0.002–0.04).

All in all, the authors concluded that Spike protein and excipients of COVID-19 vaccines (like PEG2000 and polysorbate 80) could trigger T cell-mediated cytotoxicity, which in turn contributes to the pathogenesis of immune-mediated alopecia associated with COVID-19 vaccines.

What are excipients?

Before we go on, it’s helpful to talk a bit about excipients. Excipients are added to a vaccine for a specific purpose. These include things like preservatives to prevent contamination (ie thimersol), adjuvants to stimulate a stronger immune response (ie aluminum salts) and stabilizers to help keep the vaccine functioning optimally during its transportation or stage (ie certain sugars)

Immediate‐type hypersensitivity has been described to several excipients with most reports on polyethylene glycols (PEGs) and the structurally related polysorbates. PEG 2000 is used in the mRNA vaccines from Pfizer/BioNTech  and Moderna and polysorbate 80 in viral vector vaccines from several other companies including AstraZeneca.  

PEG 2000 is really an important excipient for us to know about in the COVID era. It’s found in the mRNA vaccines. The mRNA molecules contained in the Pfizer and Moderna vaccines are stabilized by lipid nanoparticles, which are “PEGylated” to improve delivery to target cells. Now, PEG is obtained from the polymerization of ethylene glycol and can be found at different molecular weights (MW) depending on the chain length. Higher molecular weight PEGs are more likely to cause allergy. The PEG contained in mRNA-based anti-SARS-CoV-2 vaccines has a molecular weight of 2000 kDa (and that’s why it’s called PEG 2000). PEG 2000 is well known to be a potential culprit molecule in hypersensitivity reactions.

Polysorbate is found in the Astrazeneca vaccine. Polysorbates help with the overall solubility of the anti-SARS-CoV-2 vaccine. Recently, increased attention to PS allergy has arisen.

Treatment Outcomes Quite Good in COVID Associated AA

In this paper, the authors also outlined how patients were treated and what sort of hair regrowth they experienced. COVID related AA has been reported to be difficult to treat in other studies. In this study, 52 % had complete response to treatment, 41 % had partial and 7% had no response. Treatments included topical therapies in 100% of patients (minoxidil, DPCP and topical steroids) and 81 % had systemic treatments (methotrexate, cyclosporine, baricitinib, tofacitinib and systemic steroids).  In this study 92.6% of the patients with COVID-19 vaccine- related AA reached either complete or partial remission.

Discussion.

This is an interesting study. It is the largest cohort study to date to provide data on the clinical characteristics and comprehensive immune profiles of patients with alopecia areata due to COVID-19 vaccines.

The authors pinpoint that the vaccine excipients of mRNA COVID-19 vaccines (ie PEG 2000 and polysorbate 80) were regarded as the main culprit.   

Taken together, the authors propose that some patients develop AA after COVID-19 vaccinations through specific CD4+ and CD8+mediated immune reactions triggered by vaccine excipients or spike protein.

The authors found that the ANA level, total IgE, and peripheral eosinophil count were significantly elevated in the patients with COVID-19 vaccine-related AA compared with those in the tolerant controls. It may be possible that these sorts of laboratory data can help physicians in the diagnosis of AA induced by vaccines in the clinical setting.

REFERENCE

Wang C-W et al. Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations. Clin Immunol. 2023 Oct:255:109737.