New: Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis

[Wolfgang Amadeus]

Good Article!

 

[Blazer95]

as always this may work for some, but not all. for me vitamin D has always been harmful. my calcitriol/calcidiol has always been out of balance since disease beginn.

does look like someone put thought into it though.

 

[Manuel]

𝐂𝐡𝐞𝐜𝐤 𝐘𝐨𝐮𝐫 𝐂𝐨𝐫𝐭𝐢𝐬𝐨𝐥 𝐋𝐞𝐯𝐞𝐥𝐬

Many patients with ME/CFS and Long COVID find that their cortisol levels appear normal based on morning tests alone. However, a single morning measurement does not reflect the entire circadian rhythm of cortisol. For an accurate assessment, it is crucial to perform saliva cortisol testing throughout the day, measure 24-hour urine cortisol, and test for ACTH levels or the presence of anti-ACTH autoantibodies.

Symptoms that could indicate that you may have hypocortisolism:
𝐏𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐟𝐚𝐭𝐢𝐠𝐮𝐞: Constant fatigue, especially intense in the morning.
𝐏𝐨𝐬𝐭-𝐞𝐱𝐞𝐫𝐭𝐢𝐨𝐧𝐚𝐥 𝐟𝐚𝐭𝐢𝐠𝐮𝐞: Extreme exhaustion after physical or mental activities, even moderate.
𝐍𝐨𝐧-𝐫𝐞𝐬𝐭𝐨𝐫𝐚𝐭𝐢𝐯𝐞 𝐬𝐥𝐞𝐞𝐩: Feeling of not having rested well, despite getting enough sleep.
𝐆𝐚𝐬𝐭𝐫𝐨𝐢𝐧𝐭𝐞𝐬𝐭𝐢𝐧𝐚𝐥 𝐩𝐫𝐨𝐛𝐥𝐞𝐦𝐬: Nausea, abdominal pain or diarrhea, especially in the morning or in stressful situations.
𝐖𝐨𝐫𝐬𝐞𝐧𝐢𝐧𝐠 𝐢𝐧 𝐬𝐭𝐫𝐞𝐬𝐬𝐟𝐮𝐥 𝐬𝐢𝐭𝐮𝐚𝐭𝐢𝐨𝐧𝐬: aggravation of symptoms during physical or emotional stress.
𝐀𝐧𝐱𝐢𝐞𝐭𝐲 𝐚𝐧𝐝 𝐝𝐞𝐩𝐫𝐞𝐬𝐬𝐢𝐨𝐧: Increased tendency to anxiety or depression due to difficulty in handling stress.
𝐌𝐮𝐬𝐜𝐥𝐞 𝐚𝐧𝐝 𝐣𝐨𝐢𝐧𝐭 𝐩𝐚𝐢𝐧: Generalized aches and pains with no clear cause.
𝐇𝐲𝐩𝐨𝐠𝐥𝐲𝐜𝐞𝐦𝐢𝐚: Low blood sugar levels causing dizziness, weakness and irritability, especially between meals or after exertion.
𝐃𝐞𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐥𝐢𝐛𝐢𝐝𝐨: Reduced sex drive due to the impact of cortisol on hormone balance.
𝐃𝐢𝐟𝐟𝐢𝐜𝐮𝐥𝐭𝐲 𝐜𝐨𝐧𝐜𝐞𝐧𝐭𝐫𝐚𝐭𝐢𝐧𝐠: Memory and concentration problems due to lack of energy.
𝐃𝐲𝐬𝐚𝐮𝐭𝐨𝐧𝐨𝐦𝐢𝐚: Problems in the regulation of the autonomic nervous system, such as variations in heart rate.

More information on hypocortisolemia in these diseases:
https://x.com/manruipa/status/1826252428213211182

Share it with other patients so they can understand their own disease.

#LongCOVID #PostVaccinalSyndromes #MECFS

 

[Manuel]

𝐇𝐨𝐰 𝐦𝐲 𝐟𝐚𝐭𝐡𝐞𝐫 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐞𝐝 𝐬𝐲𝐦𝐩𝐭𝐨𝐦𝐬 𝐨𝐟 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐟𝐭𝐞𝐫 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 𝐰𝐢𝐭𝐡 𝐈𝐂𝐈𝐬
When I wrote the article comparing ME/CFS and Long COVID with the symptoms developed by some patients treated with ICIs who carry HLA-II susceptible alleles, I never imagined that my father would later receive the same treatment to cope with the cancer he has developed.

After several doses of Immune checkpoint inhibitors (ICIs), my father began to experience fatigue, dysautonomia, diarrhea, dysphagia, bloating, cognitive impairment, slowed thinking and speech, nasal congestion, runny nose, post-exertional fatigue, among other symptoms. It is as if the ICIs “recreate” the characteristic symptoms of ME or Long COVID by inducing immune hyperactivity and increasing the risk of developing autoimmunity in patients with susceptible HLA-II alleles.

Observing these symptoms, we suggested to the physician to check his cortisol levels. To our surprise, it was confirmed that he had developed hypocortisolism, something I had feared since I learned that he also carries the HLA-DR15 allele, as do I, who am homozygous for that variant. After the diagnosis of hypocortisolism, he was prescribed hydrocortisone replacement therapy, and in just 24 hours, his symptoms disappeared, leaving only some fatigue at night.

In my case, after my hospitalization in 2013, I also received cortisol replacement therapy due to my extremely low ACTH and cortisol levels, in addition to inflammation in the adenohypophysis detected by MRI. However, after a year of treatment, it was withdrawn because morning cortisol tests apparently showed normal levels. As I have discussed in another post, a single morning test does not give a complete picture of the circadian cortisol rhythm. Since then, I have not gone back on hydrocortisone, believing that my only problem was chronic EBV infection.

Unfortunately, I know of very few patients who have had their cortisol levels tested and had a pituitary MRI in the early stages of their symptoms. In my case, the HLA-DR15 allele made me vulnerable to EBV infection, resulting in a failure to control infected cells, causing chronic immune hyperactivity due to the constant presence of viral antigens. In my father's case, therapy with ICIs triggered immune hyperactivity by inhibiting immune checkpoints, allowing the immune system to attack healthy tissues and generate autoimmunity, with autoimmune hypophysitis being one of the most common manifestations. However, not all patients treated with ICIs develop these autoimmune diseases, and it has been linked primarily to those who carry certain susceptible HLA-II alleles, such as HLA-DR15.

Therefore, both my father and I, sharing the HLA-DR15 allele, have a genetic susceptibility that leads to an exaggerated hyperresponsiveness to certain specific antigens. In my father, this hyperactivation was induced by treatment, whereas in my case it was a consequence of infection. I do not know the other HLA-II allele that my father carries, but since I am homozygous for HLA-DR15, it is possible that I am at greater risk for this hyperactivation, as the two HLA-II alleles that we both carry are co-expressed. The difference is that, if there has been no significant damage to my father's pituitary, he could regain normal ACTH secretion after stopping treatment. In my case, as the chronic infection that triggers hyperactivation and autoimmunity against the pituitary persists, the problem will continue.

Having said all of the above, it is important to note that many patients with ME/CFS or Long COVID might think that with hydrocortisone replacement therapy alone they should get better from all symptoms, and this is not the case. This is evident in both my father and other patients treated with ICIs, as these patients do not face the other consequences caused by a chronic infection. Therefore, patients with ME/CFS and Long COVID who have permanent pituitary damage, in addition to receiving hydrocortisone replacement doses, should also consider antiviral treatment to prevent viral reactivation and reduce the viral reservoirs responsible for their immune hyperactivation and autoimmunity.

It would be extremely valuable to compare patients treated with ICIs who develop hypophysitis with those with ME/CFS or Long COVID who present with pituitary involvement. Our research group would like to explore this line and analyze other markers related to this pathophysiology, but currently we do not have the necessary funds to carry it out. If you know of any calls for proposals or any organization interested in funding us, we would be grateful if you could let us know. We are also open to collaborate with other centers.

Here is more information about the relationship between ICIs, ME/CFS and Long COVID:

https://x.com/manruipa/status/1826252428213211182

If you found it useful, please share it so that other patients can better understand their disease.

 

[beingsamiracle]

Interesting, I just started HC and will see how that goes. Based on your research, which antivirals are recommended for chronic EBV related CFS?

 

[Manuel]

Interesting, I just started HC and will see how that goes. Based on your research, which antivirals are recommended for chronic EBV related CFS?

The Lerner protocol with valacyclovir is usually recommended against EBV. In my case I have been on valacyclovir chronically for 6 years.

 

[Manuel]

𝐄𝐥𝐞𝐯𝐚𝐭𝐞𝐝 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧 𝐢𝐧 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐰𝐢𝐭𝐡 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐚𝐧𝐝 𝐌𝐄/𝐂𝐅𝐒: 𝐩𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐝𝐚𝐦𝐚𝐠𝐞 𝐨𝐫 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧𝐨𝐦𝐚?


We know that 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧 𝐞𝐥𝐞𝐯𝐚𝐭𝐢𝐨𝐧𝐬 can be a sign of pituitary damage or the presence of a 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧𝐨𝐦𝐚 (benign prolactin-producing tumor). However, many patients with 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬 (𝐌𝐄/𝐂𝐅𝐒) or 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 have experienced elevated prolactin levels without a prolactinoma being detected. Why does this occur?

In many of these cases, the elevation of prolactin could be explained by the “𝐬𝐭𝐚𝐥𝐤 𝐞𝐟𝐟𝐞𝐜𝐭,” a phenomenon that occurs when there is a 𝐝𝐢𝐬𝐫𝐮𝐩𝐭𝐢𝐨𝐧 𝐢𝐧 𝐝𝐨𝐩𝐚𝐦𝐢𝐧𝐞𝐫𝐠𝐢𝐜 𝐢𝐧𝐡𝐢𝐛𝐢𝐭𝐢𝐨𝐧 of prolactin due to pituitary inflammation. This may be caused by a condition known as 𝐚𝐝𝐞𝐧𝐨𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬, related to the autoimmune or inflammatory dysfunction seen in Long COVID and ME/CFS, resulting in a transient increase in prolactin without a tumor present.

In addition, if 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧𝐨𝐦𝐚 were to develop in the pituitary, this could also be a sign that there was prior inflammatory damage to the gland. 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐥𝐲𝐦𝐩𝐡𝐨𝐜𝐲𝐭𝐢𝐜 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 may not only cause the stalk effect, but, due to the production of 𝐩𝐫𝐨𝐢𝐧𝐟𝐥𝐚𝐦𝐦𝐚𝐭𝐨𝐫𝐲 𝐜𝐲𝐭𝐨𝐤𝐢𝐧𝐞𝐬, could create a 𝐦𝐢𝐜𝐫𝐨𝐞𝐧𝐯𝐢𝐫𝐨𝐧𝐦𝐞𝐧𝐭 conducive to the growth of pituitary adenomas, such as prolactinoma. This action suggests that intrinsic cytokines may play an important role in the pathogenesis of pituitary adenomas.


𝐏𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧 𝐚𝐧𝐝 𝐢𝐭𝐬 𝐫𝐨𝐥𝐞 𝐢𝐧 𝐥𝐲𝐦𝐩𝐡𝐨𝐜𝐲𝐭𝐢𝐜 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬
Prolactin, in addition to being a hormone, also has functions in the immune system. It has been proposed that 𝐞𝐥𝐞𝐯𝐚𝐭𝐞𝐝 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧 𝐥𝐞𝐯𝐞𝐥𝐬 in lymphocytic hypophysitis may play a role in activating the inflammatory process in the pituitary. Prolactin could act in three phases of the autoimmune process:

𝐅𝐢𝐫𝐬𝐭 𝐩𝐡𝐚𝐬𝐞: prolactin could activate pituitary 𝐟𝐨𝐥𝐥𝐢𝐜𝐥𝐞-𝐬𝐭𝐞𝐥𝐥𝐚𝐭𝐞 𝐜𝐞𝐥𝐥𝐬, which are professional antigen-presenting cells, increasing the expression of MHC class II molecules and co-stimulatory molecules such as B7.1, B7.2 and CD40. These cells are key in the activation of T lymphocytes in the immune response.
𝐒𝐞𝐜𝐨𝐧𝐝 𝐩𝐡𝐚𝐬𝐞: Prolactin could also induce an increased release of 𝐈𝐅𝐍-γ by cytotoxic T lymphocytes infiltrating the pituitary gland, promoting increased inflammatory activity and tissue damage.
𝐓𝐡𝐢𝐫𝐝 𝐩𝐡𝐚𝐬𝐞: In a later phase, prolactin could stimulate the production of 𝐚𝐧𝐭𝐢-𝐩𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐚𝐧𝐭𝐢𝐛𝐨𝐝𝐢𝐞𝐬 (𝐀𝐏𝐀) by B lymphocytes infiltrating the gland, contributing to the destruction of pituitary cells.

𝐏𝐡𝐚𝐬𝐞 𝐫𝐞𝐟𝐞𝐫𝐞𝐧𝐜𝐞: https://link.springer.com/article/10.1007/s11102-005-5082-5

This inflammatory cycle suggests that 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧 is not only elevated due to pituitary damage, but may have an active role in the maintenance and amplification of the autoimmune process. This process is more likely in patients with 𝐬𝐮𝐬𝐜𝐞𝐩𝐭𝐢𝐛𝐥𝐞 𝐇𝐋𝐀-𝐈𝐈 𝐚𝐥𝐥𝐞𝐥𝐞𝐬, which predispose to increased activation of the immune system.

𝐂𝐥𝐢𝐧𝐢𝐜𝐚𝐥 𝐢𝐦𝐩𝐚𝐜𝐭
𝐋𝐲𝐦𝐩𝐡𝐨𝐜𝐲𝐭𝐢𝐜 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 tends to dysregulate 𝐀𝐂𝐓𝐇 first, followed by 𝐠𝐨𝐧𝐚𝐝𝐨𝐭𝐫𝐨𝐩𝐢𝐧𝐬 (LH and FSH), 𝐓𝐒𝐇 and finally 𝐠𝐫𝐨𝐰𝐭𝐡 𝐡𝐨𝐫𝐦𝐨𝐧𝐞, so isolated hormone deficits are rare. Unlike the other hormones, 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧 may behave differently in cases of lymphocytic hypophysitis. Instead of decreasing like the others, it is common to observe 𝐞𝐥𝐞𝐯𝐚𝐭𝐞𝐝 𝐩𝐫𝐨𝐥𝐚𝐜𝐭𝐢𝐧 𝐥𝐞𝐯𝐞𝐥𝐬, mainly due to the stem effect and, potentially, because of its role in the immune response.

𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐢𝐬 𝐥𝐢𝐧𝐤: https://x.com/manruipa/status/1843239388546773007

𝐈𝐟 𝐲𝐨𝐮 𝐚𝐫𝐞 𝐚 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 𝐨𝐫 𝐌𝐄/𝐂𝐅𝐒 𝐩𝐚𝐭𝐢𝐞𝐧𝐭, 𝐫𝐞𝐦𝐞𝐦𝐛𝐞𝐫 𝐭𝐨 𝐠𝐞𝐭 𝐲𝐨𝐮𝐫 𝐩𝐢𝐭𝐮𝐢𝐭𝐚𝐫𝐲 𝐡𝐨𝐫𝐦𝐨𝐧𝐞𝐬 𝐭𝐞𝐬𝐭𝐞𝐝 to identify possible hormone dysregulation that could be affecting your health.

𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐨𝐭𝐡𝐞𝐫 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐚𝐧𝐝 𝐝𝐨𝐜𝐭𝐨𝐫𝐬 to help them better understand the disease. Also, I will be posting more details about infection-related autoimmune hypophysitis, stay tuned for upcoming updates!

 

[Angel Bryan]

I am here due HPV vaccine injury. I don't have fatigue yet but a lot of other ME/CFS symptoms.

Currently panic, anxiety and sensitivity to light and sounds are my main symptoms. Does this sounds like pituitary damage?

 

[Manuel]

𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐋𝐲𝐦𝐩𝐡𝐨𝐜𝐲𝐭𝐢𝐜 𝐇𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 (𝐀𝐋𝐇): 𝐓𝐡𝐞 𝐊𝐞𝐲 𝐈𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐇𝐋𝐀.
This autoimmune disease will see an increase in its diagnosis in the coming years. 𝐖𝐞 𝐡𝐚𝐝 𝐢𝐭 𝐢𝐧 𝐟𝐫𝐨𝐧𝐭 𝐨𝐟 𝐮𝐬 𝐚𝐥𝐥 𝐚𝐥𝐨𝐧𝐠.For years, 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐥𝐲𝐦𝐩𝐡𝐨𝐜𝐲𝐭𝐢𝐜 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 (𝐀𝐋𝐇) has been present in a variety of diseases, but we didn't recognize its true impact. Hypophysitis is an inflammation of the pituitary gland that can lead to hormonal failure and glandular atrophy, causing hypocortisolism. This condition has been linked to multiple causes, including autoimmune factors, infections and certain cancer treatments. Its presence has been observed in diseases such as 𝐌𝐲𝐚𝐥𝐠𝐢𝐜 𝐄𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬/𝐂𝐡𝐫𝐨𝐧𝐢𝐜 𝐅𝐚𝐭𝐢𝐠𝐮𝐞 𝐒𝐲𝐧𝐝𝐫𝐨𝐦𝐞 (𝐌𝐄/𝐂𝐅𝐒), 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, 𝐩𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐥 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬 and following the use of Immune Checkpoint Inhibitors (ICIs).

𝐓𝐡𝐞 𝐧𝐚𝐦𝐞 𝐫𝐞𝐟𝐥𝐞𝐜𝐭𝐬 𝐭𝐡𝐞 𝐜𝐚𝐮𝐬𝐞! In the name of the disease, ALH, we see a mirror of its underlying driver: the HLA predisposition that explains the autoimmune attack on the pituitary gland.

𝐇𝐋𝐀-𝐈𝐈 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐩𝐫𝐞𝐝𝐢𝐬𝐩𝐨𝐬𝐢𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐢𝐦𝐦𝐮𝐧𝐞 𝐫𝐞𝐬𝐩𝐨𝐧𝐬𝐞.
The main mechanism underlying autoimmune hypophysitis appears to be related to a genetic predisposition, specifically in individuals with HLA-II alleles such as the HLA-DR15-DQ6 haplotype. This haplotype is common in individuals with autoimmune diseases such as multiple sclerosis (MS) or systemic lupus erythematosus (SLE), where exposure to certain pathogens, such as Epstein-Barr virus (EBV), can trigger an HLA-II-mediated autoimmune response. This pattern is repeated in conditions such as ME/CFS, Long COVID, post-vaccinal syndromes or the use of ICIs, where exposure to viral antigens or immunomodulatory treatments can trigger an exaggerated immune response that compromises pituitary function.

The 𝐇𝐋𝐀-𝐃𝐑𝟏𝟓-𝐃𝐐𝟔 𝐡𝐚𝐩𝐥𝐨𝐭𝐲𝐩𝐞, considered ancestral, has an increased ability to recognize a wide variety of antigens, which increases the likelihood of exacerbated immune responses to pathogens or external stimuli such as vaccines or immunotherapies. In these individuals, antigens presented by HLA-II trigger immune hyperactivation, releasing proinflammatory cytokines such as 𝐓𝐍𝐅-α, 𝐈𝐅𝐍-γ 𝐚𝐧𝐝 𝐈𝐋-𝟔.

𝐈𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐞𝐫𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬.
The increase in these inflammatory cytokines is key in the development of autoimmune hypophysitis, as they not only inflame the pituitary, but also affect the proliferation and growth of pituitary cells. In individuals with susceptible HLA-II alleles, such as the HLA-DR15-DQ6 haplotype, uncontrolled cytokine production can induce chronic hypophysitis. Over time, this inflammation can lead to hormone insufficiency (hypocortisolism) and even to the development of pituitary adenomas.

This phenomenon has been observed in several contexts:
𝐕𝐢𝐫𝐚𝐥 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧𝐬 such as SARS-CoV, SARS-CoV-2 and EBV, which trigger a massive increase in proinflammatory cytokines.
𝐏𝐨𝐬𝐭-𝐯𝐚𝐜𝐜𝐢𝐧𝐚𝐭𝐢𝐨𝐧 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞𝐬, where vaccine antigens, such as SARS-CoV-2, induce immune hyperactivation with acute cytokine release.
𝐔𝐬𝐞 𝐨𝐟 𝐈𝐦𝐦𝐮𝐧𝐞 𝐂𝐡𝐞𝐜𝐤𝐩𝐨𝐢𝐧𝐭 𝐈𝐧𝐡𝐢𝐛𝐢𝐭𝐨𝐫𝐬 (𝐈𝐂𝐈𝐬), such as CTLA-4 or PD-1 inhibitors, which also increase immune hyperactivation, elevating TNF-α and IL-6 levels, and are clearly associated with immunotherapy-induced hypophysitis.
𝐏𝐚𝐭𝐡𝐨𝐠𝐞𝐧-𝐭𝐫𝐢𝐠𝐠𝐞𝐫𝐞𝐝 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬: HLA-II alleles predisposing to the development of hypophysitis may overlap with those predisposing to autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, Crohn's disease, rheumatoid arthritis, type 1 diabetes, Graves' disease or Sjögren's syndrome, among others.

The common pattern in these cases is HLA-II-mediated genetic predisposition, which increases susceptibility to develop autoimmune hypophysitis.

𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐦𝐨𝐫𝐞 𝐩𝐡𝐲𝐬𝐢𝐜𝐢𝐚𝐧𝐬 𝐚𝐧𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬! It is crucial that this disease stops being underdiagnosed.

𝐀𝐧𝐝 𝐟𝐨𝐥𝐥𝐨𝐰 𝐮𝐬 𝐟𝐨𝐫 𝐦𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐨𝐧 𝐡𝐨𝐰 𝐭𝐨 𝐢𝐦𝐩𝐫𝐨𝐯𝐞 𝐚𝐧𝐝 𝐭𝐫𝐞𝐚𝐭 𝐭𝐡𝐢𝐬 𝐩𝐚𝐭𝐡𝐨𝐥𝐨𝐠𝐲.

𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧: https://x.com/manruipa/status/1844701396014121037

 

[Manuel]

I am here due HPV vaccine injury. I don't have fatigue yet but a lot of other ME/CFS symptoms.

Currently panic, anxiety and sensitivity to light and sounds are my main symptoms. Does this sounds like pituitary damage?

Yes, it is also common in patients with primary/secondary adrenal insufficiency. Try to have the imaging and lab tests that I uploaded to the protocol evaluated to rule out any damage to the pituitary gland.

 

[Violeta]

This is interesting because I had been wondering about dopamine deficiency, of which I have symptoms.

And I was thinking about Angel Bryan's symptoms, they sound like dopamine deficiency symptoms, and I see that dopamine is made by the adrenals, too.

Dopamine, epinephrine and norepinephrine are the main catecholamines (a label based on having part of the same molecular structure). These hormones are made by your adrenal gland, a small hat-shaped gland located on top of each of your kidneys.

And I didn't know this:
Dopamine is a neurotransmitter that regulates the secretion of hormones in the pituitary gland:

So it's kind of a vicious cycle.

 

[Angel Bryan]

Yes, it is also common in patients with primary/secondary adrenal insufficiency. Try to have the imaging and lab tests that I uploaded to the protocol evaluated to rule out any damage to the pituitary gland.

I've seen that those symptoms are common between not just vaccine injured people but all ME/CFS patients.

Does that means all of us have pituitary damage and adrenal insufficiency?

This is interesting because I had been wondering about dopamine deficiency, of which I have symptoms.

Which are your symptoms of dopamine deficiency?

 

[Violeta]

I've seen that those symptoms are common between not just vaccine injured people but all ME/CFS patients.

Does that means all of us have pituitary damage and adrenal insufficiency?

Which are your symptoms of dopamine deficiency?

From reading Manuel's messages, I don't think it means that we all have pituitary damage, but I'll let Manuel answer that.

I found this list, and I have all of them. I've also had the symptoms you mentioned, along with orthostatic hypotension and restless leg.

• You lack motivation, “the drive.”
• You're tired.
• You can't concentrate.
• You're moody or anxious.
• You don't feel pleasure from previously enjoyable experiences.
• You're depressed; you feel hopeless.
• You have a low sex drive.
• You have trouble sleeping or have disturbed sleep.

I've been dealing with the orthostatic hypotension, restless leg with Butcher's Broom and tyrosine, and they sometimes help with disturbed sleep.

 

[Manuel]

𝐌𝐚𝐣𝐨𝐫 𝐒𝐭𝐮𝐝𝐲 𝐨𝐧 𝐭𝐡𝐞 𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐒𝐋𝐄 𝐌𝐚𝐲 𝐏𝐫𝐨𝐯𝐢𝐝𝐞 𝐅𝐮𝐫𝐭𝐡𝐞𝐫 𝐂𝐥𝐮𝐞𝐬 𝐭𝐨 𝐭𝐡𝐞 𝐎𝐫𝐢𝐠𝐢𝐧 𝐨𝐟 𝐌𝐄/𝐂𝐅𝐒 𝐚𝐧𝐝 𝐋𝐨𝐧𝐠 𝐂𝐨𝐯𝐢𝐝

Recently, another study has shed light on the importance of MHC-II (Major Histocompatibility Complex class II) or HLA-II molecules in humans and their interaction with autoreactive T cells in the pathogenesis of systemic lupus erythematosus (SLE). This discovery is not only crucial for understanding SLE, but also has significant implications for other autoimmune conditions, such as multiple sclerosis, and for more recent phenomena such as Long Covid and myalgic encephalomyelitis.

𝐖𝐡𝐚𝐭 𝐃𝐨𝐞𝐬 𝐭𝐡𝐞 𝐒𝐭𝐮𝐝𝐲 𝐑𝐞𝐯𝐞𝐚𝐥?

The study focuses on how the presentation of 𝐧𝐞𝐨𝐚𝐮𝐭𝐨𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬 by MHC-II molecules contributes to the activation of autoreactive T cells, leading to the development of autoimmune diseases. Here are some key findings:

𝐄𝐱𝐩𝐚𝐧𝐬𝐢𝐨𝐧 𝐨𝐟 𝐀𝐮𝐭𝐨𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐞 𝐓 𝐂𝐞𝐥𝐥𝐬: In patients with SLE, a significant number of CD4+ T cells expand clonally, recognizing altered self antigens. This process is essential for the production of autoantibodies that attack one's own tissues.
𝐑𝐨𝐥𝐞 𝐨𝐟 𝐭𝐡𝐞 𝐈𝐧𝐯𝐚𝐫𝐢𝐚𝐧𝐭 𝐂𝐡𝐚𝐢𝐧 (𝐈𝐢): The invariant chain (Ii) is essential for proper antigen presentation. Reduction of its expression has been shown to be related to the occurrence of autoimmune diseases, as observed in genetically modified mice.
𝐈𝐦𝐩𝐚𝐜𝐭 𝐨𝐟 𝐕𝐢𝐫𝐚𝐥 𝐑𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧: Epstein-Barr virus (EBV) reactivation can decrease Ii expression, facilitating neoautoantigen presentation and thus contributing to autoimmunity.

𝐁𝐫𝐨𝐚𝐝𝐞𝐫 𝐈𝐦𝐩𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧𝐬.
This study reveals how 𝐯𝐢𝐫𝐚𝐥 𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐚𝐭𝐢𝐨𝐧𝐬, such as those of 𝐄𝐩𝐬𝐭𝐞𝐢𝐧-𝐁𝐚𝐫𝐫 𝐯𝐢𝐫𝐮𝐬 (𝐄𝐁𝐕), can trigger autoimmune diseases by altering antigen presentation and activating autoreactive T cells. This is key to understanding the development of conditions such as 𝐦𝐮𝐥𝐭𝐢𝐩𝐥𝐞 𝐬𝐜𝐥𝐞𝐫𝐨𝐬𝐢𝐬 (𝐌𝐒) and 𝐦𝐲𝐚𝐥𝐠𝐢𝐜 𝐞𝐧𝐜𝐞𝐩𝐡𝐚𝐥𝐨𝐦𝐲𝐞𝐥𝐢𝐭𝐢𝐬/𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐟𝐚𝐭𝐢𝐠𝐮𝐞 𝐬𝐲𝐧𝐝𝐫𝐨𝐦𝐞 (𝐌𝐄/𝐂𝐅𝐒), where EBV is one of the pathogens that plays a central role.

In 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃, SARS-CoV-2 could act as an added factor, enhancing EBV reactivation and autoimmune activation in people with previous EBV viral infections, exacerbating the disease. Even SARS-CoV-2 could be solely responsible for the development of autoimmunity by its molecular mimicry with self antigens, such as ACTH, in patients with susceptible HLA-II alleles.

𝐀𝐫𝐭𝐢𝐜𝐥𝐞: https://www.sciencedirect.com/science/article/pii/S0092867424009139

Attached is information from 𝐨𝐮𝐫 𝐫𝐞𝐯𝐢𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞 on how EBV-promoted neoantigen formation promotes the development of autoimmune diseases. Example: presentation of native cellular autoantigens or viral 𝐄𝐁𝐍𝐀-𝟏 via MHC-II/gp42, which can undergo post-translational modifications, such as citrullination, and form neoantigens, could trigger the activation of autoreactive CD4 T cells and the formation of autoantibodies against tissue cells.

𝐎𝐮𝐫 𝐫𝐞𝐯𝐢𝐞𝐰 𝐚𝐫𝐭𝐢𝐜𝐥𝐞: https://www.mdpi.com/2076-0817/11/8/831


𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧: https://x.com/manruipa/status/1845790084538225031

 

[Manuel]

𝐍𝐞𝐰 𝐝𝐢𝐬𝐜𝐨𝐯𝐞𝐫𝐲 𝐚𝐛𝐨𝐮𝐭 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃: 𝐀𝐬 𝐰𝐞 𝐚𝐥𝐫𝐞𝐚𝐝𝐲 𝐤𝐧𝐞𝐰, 𝐇𝐋𝐀-𝐈𝐈 𝐚𝐫𝐞 𝐭𝐡𝐞 𝐤𝐞𝐲 .

Some of you may already know me from my posts on networks, where I have been claiming for years that the key to 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and 𝐌𝐄/𝐂𝐅𝐒 lies in 𝐬𝐮𝐬𝐜𝐞𝐩𝐭𝐢𝐛𝐥𝐞 𝐇𝐋𝐀-𝐈𝐈 𝐚𝐥𝐥𝐞𝐥𝐞𝐬, which when encountering a specific antigen, promote immune hyperactivity and autoimmunity. As occurs in any other known autoimmune disease.

Today I am happy to see that our hypothesis continues to gain strength, and this study confirms it! Susceptible HLA-II alleles have been identified in Long COVID, such as 𝐇𝐋𝐀-𝐃𝐑𝐁𝟏*𝟏𝟏:𝟎𝟒. This brings us closer to demonstrating that both Long COVID and ME/CFS are 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬, triggered by persistent infection in patients with susceptible HLA-II alleles, which prevent effective infection control and, at the same time, generate autoimmunity.

The preprint, conducted by @23andMeResearch, is the largest to date, involving people of diverse ancestries. Its main finding is the 𝐚𝐬𝐬𝐨𝐜𝐢𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐭𝐡𝐞 𝐇𝐋𝐀-𝐃𝐑𝐁𝟏*𝟏𝟏:𝟎𝟒 𝐚𝐥𝐥𝐞𝐥𝐞 with the risk of developing Long COVID. These 𝐇𝐋𝐀-𝐈𝐈 molecules play a key role in the immune system, presenting viral antigens to T lymphocytes and activating the immune response. Therefore, HLA-II molecules are also involved in the autoimmune response.

In addition, other important findings were identified:

𝐀𝐁𝐎, another gene related to COVID-19 severity, which would also influence the risk of Long COVID.

Genetic connections between 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and conditions such as 𝐌𝐄/𝐂𝐅𝐒, 𝐝𝐞𝐩𝐫𝐞𝐬𝐬𝐢𝐨𝐧 𝐚𝐧𝐝 𝐟𝐢𝐛𝐫𝐨𝐦𝐲𝐚𝐥𝐠𝐢𝐚.

𝐀𝐫𝐭𝐢𝐜𝐥𝐞: https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1

𝐒𝐡𝐚𝐫𝐞 this information to reach more researchers and patients, let's keep the research moving forward!

In the next post, I attach how 𝐚𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 may be present in patients with ME/CFS and Long COVID who have susceptible HLA-II alleles.


𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧: https://x.com/manruipa/status/1846515902025752611?s=46&t=m4Zmq5Ji7bf6LgmUbeK4pA

 

[sb4]

@Manuel I find this very interesting but as I went through the articles I tried to find SNPs I could search for on 23andMe but didn't really know what I was looking for.

Do you have a list of these at hand?

Thanks.

 

[beingsamiracle]

@Manuel do you have any information regarding safety taking low dose hydrocortisone and valtrex at the same time? Ideally a scientific citation or the like...

 

[Angel Bryan]

Autoimmunity is the worst thing that can happen to us. This is depressing.

 

[Manuel]

The Key to Long COVID and ME/CFS Is in This Table: History Repeats Itself

What we now consider a new disease has existed before under different names and causes.

Behind 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and 𝐌𝐄/𝐂𝐅𝐒 lurk autoimmune diseases that existed before.

𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐥𝐲𝐦𝐩𝐡𝐨𝐜𝐲𝐭𝐢𝐜 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 (𝐀𝐋𝐇) is not a phenomenon unique to Long COVID, ME/CFS or post-vaccinal syndromes. This same pattern had already been triggered by other 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐬, 𝐯𝐚𝐜𝐜𝐢𝐧𝐞 𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬 and even 𝐚𝐫𝐭𝐢𝐟𝐢𝐜𝐢𝐚𝐥𝐥𝐲 with Immune Checkpoint Inhibitors (ICIs).

𝐇𝐋𝐀-𝐈𝐈 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐩𝐫𝐞𝐝𝐢𝐬𝐩𝐨𝐬𝐢𝐭𝐢𝐨𝐧, along with 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧, have been the culprits all along. Conditions that once went unnoticed are now gaining recognition.

Thus, Long COVID, ME/CFS and post-vaccine COVID-19 syndrome are, in essence, autoimmune diseases, triggered by 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 𝐨𝐫 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐩𝐫𝐞𝐬𝐞𝐧𝐜𝐞 𝐨𝐟 𝐯𝐢𝐫𝐚𝐥 𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬 in patients with susceptible HLA-II alleles, which prevent effective infection control and, at the same time, generate autoimmunity. HLA-II alleles can vary by pathogen, as each has unique characteristics that can influence how the immune system recognizes and responds to it.

It is time to connect the dots and understand that the key lies in the 𝐢𝐦𝐦𝐮𝐧𝐞 𝐬𝐲𝐬𝐭𝐞𝐦 and its uncontrolled response to these stimuli.

𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐩𝐡𝐲𝐬𝐢𝐜𝐢𝐚𝐧𝐬 𝐚𝐧𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬. it's time to better diagnose these autoimmune conditions and stop underdiagnosing them!

𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧: https://x.com/manruipa/status/1846875286660431885

 

[Angel Bryan]

View attachment 54629
The Key to Long COVID and ME/CFS Is in This Table: History Repeats Itself

What we now consider a new disease has existed before under different names and causes.

Behind 𝐋𝐨𝐧𝐠 𝐂𝐎𝐕𝐈𝐃 and 𝐌𝐄/𝐂𝐅𝐒 lurk autoimmune diseases that existed before.

𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐞 𝐥𝐲𝐦𝐩𝐡𝐨𝐜𝐲𝐭𝐢𝐜 𝐡𝐲𝐩𝐨𝐩𝐡𝐲𝐬𝐢𝐭𝐢𝐬 (𝐀𝐋𝐇) is not a phenomenon unique to Long COVID, ME/CFS or post-vaccinal syndromes. This same pattern had already been triggered by other 𝐩𝐚𝐭𝐡𝐨𝐠𝐞𝐧𝐬, 𝐯𝐚𝐜𝐜𝐢𝐧𝐞 𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬 and even 𝐚𝐫𝐭𝐢𝐟𝐢𝐜𝐢𝐚𝐥𝐥𝐲 with Immune Checkpoint Inhibitors (ICIs).

𝐇𝐋𝐀-𝐈𝐈 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐩𝐫𝐞𝐝𝐢𝐬𝐩𝐨𝐬𝐢𝐭𝐢𝐨𝐧, along with 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧, have been the culprits all along. Conditions that once went unnoticed are now gaining recognition.

Thus, Long COVID, ME/CFS and post-vaccine COVID-19 syndrome are, in essence, autoimmune diseases, triggered by 𝐩𝐞𝐫𝐬𝐢𝐬𝐭𝐞𝐧𝐭 𝐢𝐧𝐟𝐞𝐜𝐭𝐢𝐨𝐧 𝐨𝐫 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐩𝐫𝐞𝐬𝐞𝐧𝐜𝐞 𝐨𝐟 𝐯𝐢𝐫𝐚𝐥 𝐚𝐧𝐭𝐢𝐠𝐞𝐧𝐬 in patients with susceptible HLA-II alleles, which prevent effective infection control and, at the same time, generate autoimmunity. HLA-II alleles can vary by pathogen, as each has unique characteristics that can influence how the immune system recognizes and responds to it.

It is time to connect the dots and understand that the key lies in the 𝐢𝐦𝐦𝐮𝐧𝐞 𝐬𝐲𝐬𝐭𝐞𝐦 and its uncontrolled response to these stimuli.

𝐒𝐡𝐚𝐫𝐞 𝐭𝐡𝐢𝐬 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐩𝐡𝐲𝐬𝐢𝐜𝐢𝐚𝐧𝐬 𝐚𝐧𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬. it's time to better diagnose these autoimmune conditions and stop underdiagnosing them!

𝐌𝐨𝐫𝐞 𝐢𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧: https://x.com/manruipa/status/1846875286660431885

In theory, that would mean that getting rid of the underlying infection (in your case EBV) will cure all the patient symptoms or the damage to the hypothalamus and autoimmunity are permanent?

How will this explain the people who suddenly recover after time?