Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium

Abstract
G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context.

Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15–16 September 2022. The symposium focused on the current knowledge of these autoantibodies' role in various diseases, such as cardiovascular, renal, infectious (COVID-19), and autoimmune diseases (e.g., systemic sclerosis and systemic lupus erythematosus).

Beyond their association with disease phenotypes, intense research related to the mechanistic action of these autoantibodies on immune regulation and pathogenesis has been developed, underscoring the role of autoantibodies targeting GPCRs on disease outcomes and etiopathogenesis. The observation repeatedly highlighted that autoantibodies targeting GPCRs could also be present in healthy individuals, suggesting that anti-GPCR autoantibodies play a physiologic role in modeling the course of diseases.

Since numerous therapies targeting GPCRs have been developed, including small molecules and monoclonal antibodies designed for treating cancer, infections, metabolic disorders, or inflammatory conditions, anti-GPCR autoantibodies themselves can serve as therapeutic targets to reduce patients' morbidity and mortality, representing a new area for the development of novel therapeutic interventions.

https://www.sciencedirect.com/science/article/abs/pii/S1568997223000447

 

"Anti-GPCR autoantibodies against the autonomic nervous system: from breast silicone implants to “dysautonomia”
Seven clinical entities that include CFS, fibromyalgia, macrophagic myofasciitis, postural orthostatic tachycardia syndrome, complex regional pain syndrome, post-human papillomavirus vaccine syndrome/human papillomavirus vaccination associated neuro-immunopathic syndrome, and sick building syndrome have been noted to share several major clinical features. The manifestations entail cognitive impairment, memory loss, sleeping disturbances, severe and extreme fatigue, widespread pain, dry mouth..."

Above seems very relevant, but is pay to view.

 

I can access it via UCL. Unfortunately the paper seems to be an extended snowstorm of poor evidence (which is what to expect from this journal by the way).

I note the following statement:
These findings, and the observation that autoantibodies targeting therapies, including immunoadsorption and rituximab treatment, improve the disease severity of at least a subset of patients, reinforce the importance of GPCR-autoantibodies in ME/CFS [65,[72], [73], [74]].

is just straight misleading. The evidence is pretty starkly negative both for the antibodies and response to treatment.

 

Haven't read the above publication and (evidently) I know little, but it strikes me that often tests for autoantibodies are poor i.e. false positives/negatives. I hope(d) that this type of technology* would improve things, but producing the target protein/antigen doesn't seem to be that easy.
It appears that we get a lot of dodgy claims re autoimmunity - some of these studies appear to rival the unblinded psychological study with subjective outcome criteria ---. We do, of course, have sound studies like Fluge & Mella (rituximab).

*"REAP uncovers functional autoantibodies in autoimmune ... Michail S. Lionakis, Aaron M. Ring
https://www.cell.com/cell-reports-methods/pdf/S2667-2375(22)00024-8.pdf