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; (2) RA as a D+V− type; (3) pSS as a D+++V−− type (glandular metabolic quiescence). The DCV-pSS score achieves r=−0.421 to −0.694 across all three pSS cohorts. Complement activation anchors the C-dimension across all three diseases (ESSDAI ρ=+0.566 in pSS). The IFN-Complement uncoupling in pSS provides a mechanistic explanation for differential anifrolumab response.