Dogan 2026 — Serum GRIN1, P2RX1, P2RY2 as FM diagnostic biomarkers

One-paragraph summary

Case-control biomarker study: 93 newly-diagnosed FM patients vs. 93 age- and sex-matched healthy controls. Serum levels of three receptor proteins implicated in central sensitization were measured by ELISA: GRIN1 (NMDA receptor NR1 subunit, glutamatergic), P2RX1 (P2X1 ATP-gated channel, purinergic), P2RY2 (P2Y2 G-protein-coupled, purinergic). All three showed strong diagnostic accuracy: GRIN1 AUC 0.817 (sens 91.4%, spec 72.0%); P2RX1 AUC 0.778 (sens 78.5%, spec 75.3%); P2RY2 AUC 0.842 (sens 92.5%, spec 80.6%) — all p<0.001. P2RY2 is the single best peripheral blood biomarker for FM in the project's evidence base to date. Combined as a panel, these may provide a clinically useful diagnostic — currently FM has no validated blood test.

Claims as triples

• serum_GRIN1_level — predicts → central_sensitization [evidence: AUC 0.817; confidence: emerging]
• serum_P2RX1_level — predicts → central_sensitization [evidence: AUC 0.778; confidence: emerging]
• serum_P2RY2_level — predicts → central_sensitization [evidence: AUC 0.842; confidence: emerging]
• GRIN1 — modulates → central_sensitization [molecular mechanism; confidence: established (NMDA-LTP)]
• P2RX1 — modulates → central_sensitization [purinergic signaling; confidence: emerging]
• P2RY2 — modulates → central_sensitization [purinergic signaling; confidence: emerging]

Methods note

n = 93 FM (newly diagnosed) + 93 age/sex-matched HC. Serum quantified by ELISA. ROC analysis with optimal cut-points reported. Authors: Dogan + collaborators (Turkish institution, exact affiliation not in available metadata). Single-site, single-cohort design.

Limitations

• Single-cohort, single-site, no replication yet. AUC values from a single cohort tend to inflate; independent replication typically reduces them by 0.05–0.10. Tier promotion of the biomarkers should require replication.
• ELISA kits for these receptors have variable validation across vendors — kit-source and antibody specificity should be checked in full text before clinical adoption.
• Newly-diagnosed FM sampling means the biomarkers may reflect early-disease state; longitudinal or established-disease cohorts could give different values.
• All three are correlated biomarkers of the same underlying glutamatergic/purinergic pathway — diagnostic gain from a panel may be modest if they're collinear.
• Specificity matters in clinical use: if 27% of healthy controls test "positive" by GRIN1 (28% by P2RX1), this is a screening rather than confirmatory tool.

Open questions raised

• Independent-cohort replication is the single most important next step. If AUC > 0.75 holds for any of the three in a second cohort, this becomes a publishable diagnostic biomarker.
• Are the three biomarkers collinear (single-construct redundancy) or independent (additive panel)? Combined ROC analysis would resolve.
• Q14 expanded: do GRIN1/P2RX1/P2RY2 levels track TSPO-PET signal (inflammatory-central subtype) or anti-SGC IgG (autoimmune subtype) — i.e., which subtype do they index?
• Are these biomarkers state (correlate with current pain intensity / disease activity) or trait (stable patient-level marker)?
• Do glutamatergic-NMDA antagonists (memantine) and purinergic antagonists (suramin variants, A317491) show preferentially better treatment response in patients with elevated baseline biomarker levels?

Triangulation notes

• The first FM-specific blood biomarker panel with reasonable diagnostic performance in the project's evidence base. Anchors serum_GRIN1_level, serum_P2RX1_level, serum_P2RY2_level as emerging biomarkers.
• Q10 (clean single-blood-draw biomarker panel) has a candidate answer.
• Combined with the autoimmune-thread Jakobsson 2026 (bile acids ↔ anti-SGC IgG), the FM diagnostic landscape now has three candidate biomarker dimensions: (1) central-glutamatergic/purinergic (Dogan 2026), (2) microbial-bile-acid-IgG (Jakobsson 2026), (3) IENFD/TSPO-PET (existing). Subtype mapping across these three is now tractable.
• Therapeutic implication: NMDA antagonists (memantine, ketamine — already used off-label for FM) and emerging P2X4/P2X7 antagonists may benefit biomarker-positive patients preferentially. Subtype-stratified trials become designable.

Bridges

• No new cross-domain bridges, but reinforces the biomarker-panel approach to subtype mapping.