DCV-Classified Autoimmune Microvascular Dysregulation: A Unified Transcriptomic Framework Revealing Disease-Specific Coupling Signatures in SLE, RA, and pSS

Systemic autoimmune diseases share microvascular dysregulation but differ fundamentally in their molecular architecture. The Autoimmune Microvascular Instability Score (AMIS) — an equal-weight ssGSEA composite of six vascular-inflammatory pathways — succeeds in SLE but fails completely in primary Sjögren's syndrome (pSS), where opposing pathway directions arithmetically cancel. This paper proposes the Displacement–Coupling–Velocity (DCV) framework as a unified theoretical architecture for classifying transcriptomic dysregulation across autoimmune diseases. Applied to seven publicly available whole-blood transcriptomic datasets (N=2,568; SLE, RA, pSS), the DCV framework reveals three distinct disease fingerprints: (1) SLE as a D+C− type (NETosis/IFN displacement + complement-endothelial coupling degradation); (2) RA as a D+V− type (NETosis-dominant displacement with metabolic velocity dysregulation); (3) pSS as a D+++V−− type (extreme IFN-driven displacement with glandular metabolic quiescence). The DCV-pSS score (IFN+Complement composite) achieves r=−0.421 to −0.694 across all three pSS cohorts, resolving the AMIS paradox. Complement activation anchors the C-dimension across all three diseases, with the strongest clinical validity in pSS (ESSDAI ρ=+0.566, p=0.001). The IFN-Complement uncoupling observed in pSS (vs. coupled D+C in SLE) provides a mechanistic explanation for differential anifrolumab response and motivates combination D+C targeting in pSS.