Antibodies Against GPCR (

[Murph]

Front Biosci (Landmark Ed). 2018 Jun 1;23:2177-2194.
Antibodies Against GPCR.
Meyer C1, Heidecke H2.
Author information
1
CellTrend GmbH, Im Biotechnologiepark TGZ II, 14943 Luckenwalde, Germany.
2
CellTrend GmbH, Im Biotechnologiepark TGZ II, 14943 Luckenwalde, Germany, heidecke@celltrend.de.
Abstract
G-protein-coupled receptors (GPCRs) are the largest family of receptors in humans. GPCRs are seven-transmembrane receptors that are activated by the binding of a ligand to the extracellular domain. In addition to the endogenous ligands, auto-antibodies (aab) can also bind to the GPCRs. They can activate different and specific cellular pathways which contribute to various diseases. In this review, the authors summarize the knowledge about antibodies targeting GPCRs and their effects and relevance in the pathogenesis of various diseases and their use in clinical diagnostics. We highlight the role of different activating anti-GPCR aab in solid organ transplantations, stem cell transplantations, systemic sclerosis, preeclampsia, chronic fatigue syndrome, cardiovascular diseases, Alzheimer's disease, and cancer.

 

[Murph]

here's the relevant sections :

5.1. Chronic Fatigue Syndrome (CFS/ME)

Chronic Fatigue Syndrome has an estimated prevalence of 0.2–0.3% (82); it is a frequent and severe chronic disease. Scheibenbogen et al. determined antibodies against alpha and beta adrenergic receptors, muscarinic cholinergic receptors 1-5, dopamine receptors, serotonin receptors, AT1R, and ETAR by ELISA (CellTrend GmbH) in sera from chronic fatigue syndrome patients (n=268) and healthy controls (n=108).

Anti-beta-2 adrenergic receptors, anti- muscarinic cholinergic receptors 3 and anti-muscarinic cholinergic receptors 4 aab were significantly elevated in CFS patients compared to controls (83). In addition, pre and post-treatment samples from 25 patients treated during the KTS-2 rituximab trial were analyzed for aab against GPCR (84, 85). In patients receiving rituximab and responded to therapy, anti-beta-2 adrenergic receptor and anti-muscarinic cholinergic receptor 4 aab signi cantly decreased. In contrast, the aab levels in non-responders did not reduce. This is the first sign that anti-beta-2 adrenergic receptor and the anti-muscarinic cholinergic receptor 4 aab could be used as a companion diagnostic for rituximab treatment in chronic fatigue syndrome.

In addition, Scheibenbogen et al. showed that immunoadsorption (IA) was effective to remove anti-beta-2 adrenergic receptors aab in chronic fatigue syndrome patients and improve their outcome (86). In detail, elevated anti-beta-2 adrenergic receptor aab rapidly decreased during IA in 9 of 10 patients. Furthermore 6 months later anti-beta-2 adrenergic receptors aab were significantly lower compared to pretreatment. A rapid improvement of symptoms was reported by 7 patients during the IA. 3 of these patients had long lasting and ongoing moderate to marked improvement for 6 - 12 months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening.

Kämpf et al. described for the first time an association between anti-muscarinic cholinergic receptors 3 and anti-muscarinic cholinergic receptors 4 aab and cancer related fatigue syndrome (87).

5.4. Orthostatic hypotension and postural tachy- cardia syndrome

Orthostatic hypotension (OH) is frequently associated with autonomic dysfunction caused by a
variety of primary or secondary autonomic disorders (99). OH of varying severity af icts up to 2% of the adult population (100). Li et al. demonstrated in a mechanistic study the association of aab directed toward the anti-beta-2 adrenergic receptors and anti- muscarinic cholinergic receptors 3 aab in patients with demonstrable orthostasis (101). In addition, Yu et al. detect anti-beta-1 adrenergic receptors, anti-beta-2 adrenergic receptors, anti-muscarinic cholinergic receptors 2, and anti-muscarinic cholinergic receptors 3 aab in sera samples from OH patients (102).

Postural tachycardia syndrome (POTS) occurs most commonly in young women of child- bearing age, less frequently in males or at older ages (103). Li et al. described elevated levels of anti-alpha-1 adrenergic receptors, anti-beta-1 adrenergic receptors, and anti-beta-2 adrenergic receptors aab (104). These ndings have been con rmed by us (own unpublished data).

 

[Murph]

@Gingergrrl this research is from your friends at Cell Trend

 

[Gemini]

In patients receiving rituximab and responded to therapy, anti-beta-2 adrenergic receptor and anti-muscarinic cholinergic receptor 4 aab significantly decreased. In contrast, the aab levels in non-responders did not reduce. This is the first sign that anti-beta-2 adrenergic receptor and the anti-muscarinic cholinergic receptor 4 aab could be used as a companion diagnostic for rituximab treatment in chronic fatigue syndrome.

@Murph, interesting, thanks for posting the highlights. [my bold]

Hopefully forthcoming rituximab trial paper(s) will describe levels of various autoantibodies before and after treatment.

 

[kendonoghue]

DOI for full text. 10.2741/4698 But Murph provided the relevant info.

 

[Murph]

@Murph, interesting, thanks for posting the highlights. [my bold]

Hopefully forthcoming rituximab trial paper(s) will describe levels of various autoantibodies before and after treatment.

I can't wait for both these fluge / Mella papers to arrive. It's plausible I guess that the Phase 3 Ritux has given them some insight that is changing how they approach / analyse the results of the cyclophosphamide study. Either way the combination of the two papers should offer a lot of insights. In fact, i'd be surprised if the two big trials generate only two papers.

There will probably be a main paper from each trial plus sub-papers on various other measures. I'm particularly interested in their hints that they spotted a problem with flow-mediated dilation (i.e. a blood flow problem) and I'd love to see a paper or two on that.

 

[Gingergrrl]

@Gingergrrl this research is from your friends at Cell Trend

Thanks for posting all of this information @Murph (although I had to laugh when you referred to my "friends" at Cell Trend ). I had one phone call (in 2016) with the head of Cell Trend which was very helpful, and is still memorable to me, but I doubt he has any memory of the call LOL.

 

[pattismith]

I just had my results from celltrend...

My Ab
anti AT1R, ETAR and alpha 1 AR are high,
M3 is at risk,
alpha2 AR positive (but not very high)

alpha 1AR is positive in POTS people, but I don't have POTS.

Agonistic Anti alpha 1AR was found in ALzheimer, with some clinical relevance. (Biosci 2018) but not in another study;

In this other study:


"Patients with Alzheimer’s and vascular dementia carried GPCR-AABs targeting the first loop of the alpha1- and the second loop of the beta2-adrenergic receptors (α1-AABs; β2-AABs).
Nearly all vascular dementia patients also carry autoantibodies targeting the endothelin A receptor (ETAR-AABs).
The majority of patients with Lewy body dementia lacked any of the GPCR-AABs. "

 

[pattismith]

I started Losartan two days ago...( AT1R blocker )


Here a recent study Juanary 2020


Cytokine
Volume 125, January 2020, 154860

Losartan modulates brain inflammation and improves mood disorders and memory impairment induced by innate immune activation: The role of PPAR-γ activation


Highlights

•
Repeated LPS injection induces persistent memory impairment and mood disorders.
•
Losartan ameliorates brain inflammation induced by systemic LPS injection.
•
Losartan improves memory impairment and anxiety induced by systemic LPS injection.
•
The beneficial actions of losartan are not mediated through a PPAR-γ activation.

Abstract
In recent years, the role of angiotensin II (Ang II) and Ang II type 1 receptor (AT1) in the crosstalk between the immune system and the central nervous system has received more attention. The present study aimed to investigate the role of losartan, an AT1 receptor blocker, in the modulation of long-lasting adverse effects of repeated systemic lipopolysaccharide (LPS) injection in the brain function.

For this purpose, 110 male BALB/c mice were administrated LPS (250 µg/kg) intraperitoneally (i.p.) for seven consecutive days.

Mice were i.p. injected with losartan (1 and 3 mg/kg) three days before and during the LPS injection.

To determine the role of PPAR-γ activation in the protective actions of losartan, GW9662, a PPAR-γ antagonist, was also co-administrated with losartan.

Then, behavioral tests, including Morris water maze (MWM), novel object recognition test, passive avoidance, forced swim test (FST), elevated plus maze, and marble burying task, were conducted.

The results demonstrated that losartan improved learning and memory impairment, attenuated anxiety-like behaviors, modulated brain inflammation and oxidative stress, and decreased amyloid-β accumulation.

Losartan was unable to improve hippocampal BDNF and IL-10 levels as well as the retention trial in the MWM task and depressive-like behaviors.

In addition, the PPAR-γ antagonist did not significantly influence the beneficial effects of losartan.

Our findings suggest that AT1R blockade can protect the brain against most long-lasting hallmark effects of systemic inflammation.

Also, based on the results, the beneficial actions of losartan were not mediated through PPAR-γ activation.

 

[andyguitar]

I started Losartan two days ago...( AT1R blocker )

Is it helping?

 

[pattismith]

Is it helping?

I thought I couldn't tolerate it, as it lowers blood pressure, and mine is already low.

So I'm surprised not to feel worse.

I suffer with vascular problems in my brain, can't tolerate too much coffee (vasoconstrictor) or too much magnesium (vasodilator), so I wish to do a trial with Losartan for two weeks and see what it can do for my brain, and also for my small fiber neuropathy/erythromelalgia.

I take only a small dose 25 mg per day.

 

[pattismith]

update: I did another trial with Losartan while having a flare of enthesitis pain, and it worsened a lot my pain, i had to stop it all

Anyone have problems with Losartan? | Page 2 | Phoenix Rising ME/CFS Forums

Another 2020 study about AT1R AAB in Lupus Nephritis:/ LN:

"The AT1R-AA titers correlated with anti-dsDNA antibody titers and with complement C3 and C4 serum levels. In the kidney biopsy, the percentage of subintimal fibrosis and the area of medial hyperplasia were greater in the AT1R-AA-positive patients. No differences in arterial pressure, carotid intima-media thickness and response to therapy were detected. In conclusion, AT1R-AAs are prevalent in active LN patients and are associated with histologic features of microvascular damage."

• DOI: 10.1177/0961203320904787