Antibodies That Don’t Block, They Activate: A New Angle on Autoimmunity and GPCRs

Watch Episode 167

Some GPCR-targeting antibodies don’t inhibit receptors. They activate them. This insight from Dr. Tom Sakmar points to a largely overlooked mechanism in disease: autoantibodies that don’t block receptors but instead activate them, potentially driving pathology. From autoimmune disorders to long COVID, we may be seeing just the tip of the iceberg.

A New Role for GPCRs in Disease

Sakmar highlights how endothelial cells, which express a wide array of GPCRs, are likely targets for antibody-based immune responses. And not all antibodies are created equal.

“Some of these antibodies actually activate the receptor and cause pathological signaling.” — Tom Sakmar

This makes them more than biomarkers — they’re potential drivers of disease.

The Tools to Detect Them

Using the multiplexed GPCR library and Luminex assay, researchers can now:

• Screen patient samples for GPCR autoantibodies

• Identify which receptor is being bound

• Determine if the antibody is activating or inhibitory

• Guide diagnostics or treatment research based on GPCR targets

Beyond Classic ELISAs

Traditional autoantibody testing relies on single-target ELISAs. Sakmar and Kotliar’s system is multiplexed and scalable, able to test hundreds of interactions from one tube of sample.

What’s Next?

Ilana Kotliar sees a future where this system is not just used for detection, but for functional screening: add ligands, track modulation, and even identify biased autoantibodies.

This is the future of GPCR immunology.

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Keyword Cloud: GPCR autoantibodies, GPCR immunology, GPCR diagnostics, Dr. GPCR ecosystem, multiplex assays