Dysregulation of anti-GPCR AAb in auto-immune diseases (muscarinic and others)

[pattismith]

GPCR auto-antibodies are antibodies against receptors like the ones Celltrend proposes (but they are many other AAb in this category):

-alpha and beta adrenergic receptors
-muscarinic receptors
-ETA receptors (EDNRA)
-AT1 receptors

this study has shown that autoimmune disease have a signature when all these auto-antibodies are tested.
Here they tested Systemic Lupus E, Systemic Sclerosis, Rheumatic Arthritis, Granulomatosis PA.

It's a pity that we don't have such a study for POTS or ME/CFS!


GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis
2018

• Otavio Cabral-Marques,
• Alexandre Marques,
• […]
• Gabriela Riemekasten

 

[pattismith]

@Murph @Gingergrrl

this article is proposing a new paradigm for autoimmune diseases, you may be interested:


"More than a century after the immunologist Paul Ehrlich proposed his theory of horror autotoxicus based on the concept that immunized animals did not produce autoantibodies (aab) in response to their own blood or blood from their own species1, a paradigm persists linking aab to the development of autoimmune diseases2.

However, aab have been found in healthy donors (HD) at preclinical stages and even in those who never develop autoimmune disorders3,4.

Furthermore, beneficial, naturally occurring aab that show protective effects against the development of immune-mediated diseases, such as type 1 diabetes and psoriasis, have recently challenged the aforementioned paradigm5.

The most common theories proposed to explain aab production are based on molecular mimicry and immune dysregulation4,6.

However, these theories mainly aim to integrate the mechanisms of aab production with the commonly accepted paradigm that associates aab with autoimmune diseases. Thus, they are unable to fully explain the occurrence of self-reactive B cells in mice and humans7 and the production of immunogobulin G (IgG) aab that are naturally present in sera from HD.

The generation of natural aab shares a common ontogeny with that of conventional antibodies, as both depend on the presentation of stimulatory antigens by dendritic cells to T and B lymphocytes4,6.

We hypothesize that, similar to the dysregulation of any biological process, such as the imbalance of cytokine synthesis by T helper (Th) cells in several pathological conditions8, the dysregulation of aab production and function may lead to autoimmune diseases. Thus, we suspect that the homeostasis of aab relationships, which are possibly a physiological part of our immune system, may break down, causing autoimmune disease."

 

[pattismith]

another article from this celltrend team

Published online 2020 Dec 15. doi: 10.3389/fimmu.2020.564526

What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases
Gabriela Riemekasten, 1 , 2 , 3 , 4 , * Frank Petersen, 2 , 3 , 4 and Harald Heidecke 5

Abstract
Expressions of G protein-coupled receptors (GPCR) on immune and tissue resident cells are the consequence of the cellular environment, which is highly variable.

As discussed here, antibodies directed to GPCR (GPCR abs), their levels and correlations to other abs, serve as biomarkers for various diseases.

They also could reflect the individual interplay between the environment and the immune system.

Thus, GPCR abs could display pathogenic chronic conditions and could help to identify disease-related pathways. Moreover, by acting as ligands to their corresponding receptors, GPCR abs modulate autoimmune as well as non-autoimmune diseases.

This article introduces GPCR abs as drivers for diseases by their capability to induce a specific signaling and by determining immune cell homeostasis.

The identification of the individual GPCR ab function is challenging but might be pivotal in the comprehension of the aetiology of diseases.

This, hopefully, will lead to the identification of novel therapeutic strategies. This article provides an overview about concepts and recent developments in research.

Accordingly, GPCR abs could represent ideal candidates for precision medicine.

Here, we introduce the term antibodiom to cover the network of abs with GPCR abs as prominent players.

 

[pattismith]

Increased and Decreased G Protein-Coupled Receptor Antibody Levels as Markers for Autoimmune And Non-Autoimmune Diseases

Increased abs against self-antigens are a feature of autoimmune diseases. Indeed, high GPCR abs are associated with several rheumatic autoimmune diseases such as with SSc, systemic lupus erythematosus (SLE), or primary Sjogren’s syndrome (2, 18–21).

In SSc, AT1R abs as well as ETAR abs are increased and predict vascular complications such as pulmonary arterial hypertension as well as mortality and response to therapies (18, 19).

Nevertheless, higher GPCR abs compared to healthy individuals are common in human pathophysiology and were also found in endocrinological diseases (Graves’ Disease or Hashimoto thyroiditis), in gynaecology (preeclampsia), cardiac diseases (heart transplantation, cardiomyopathy, chronic heart failure, orthostatic hypotension, and postural tachycardia syndrome), or in neurologic diseases such as in dementia, Alzheimer Disease, chronic fatigue syndrome (myalgic encephalomyelitis), or in complex regional pain syndromes (6, 13, 20–23).

In contrast, some diseases including autoimmune diseases are characterized by reduced levels of GPCR abs when compared to healthy donors.

Thus, patients with giant cell arteritis have lower ETAR ab levels compared to healthy donors (24) and patients with granulomatosis with polyangiitis have reduced levels of antibodies against complement receptors (2).

Furthermore, reduced levels of antibodies against ß1-adrenergic receptors are present in patients with acute coronary syndrome and are associated with a more severe disease particularly with a higher risk for early reinfarction and cardiovascular death in patients ≤ 60 years (25, 26).

Lower abs against the thrombin receptor PAR-1 are associated with ovarian cancer and with high-grade carcinoma (2, 27). Finally, decreased levels of abs against the chemokine receptor CXCR3 and CXCR4 are found in patients with progressive interstitial lung disease (28, 29).

The presence of both increased as well as reduced GPCR ab levels further strengthen the idea of the presence of physiological levels and a balanced generation of autoantibodies in human physiology and pathophysiology.

 

[pattismith]

Finally, decreased levels of abs against the chemokine receptor CXCR3 and CXCR4 are found in patients with progressive interstitial lung disease (28, 29).

in their 2021 study about primary Sjogren Disease, they noticed the same...

Results

Compared to healthy subjects, sera of patients with pSS showed significantly higher binding to β2AR and ETAR, but lower binding to C5aR1, C3aR1, CXCR3, and CXCR4.

Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 were also decreased in patients with rheumatoid arthritis.

In pSS patients, levels of anti-CXCR3 and anti-CXCR4 antibodies were negatively correlated with circulating lymphocyte counts.

Furthermore, correlation signatures of anti-GPCR antibodies changed dramatically in the patients with pulmonary involvement.