The neuro-immune gap in systemic autoimmunity: Integrated dysregulation of the HPA axis and autonomic flexibility in SLE and Sjögren's syndrome.

BACKGROUND

While systemic inflammation is the hallmark of Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SS), the failure of endogenous "anti-inflammatory brakes" remains poorly understood. The Hypothalamic-Pituitary-Adrenal (HPA) axis and the Autonomic Nervous System (ANS) constitute the body's primary neuro-immune regulatory circuit. This study investigates whether concurrent dysregulation of these two systems contributes to the persistent inflammatory state in SLE and SS.

METHODS

In this cross-sectional study, we evaluated 40 patients with Systemic Lupus Erythematosus (SLE), 40 with Sjögren's Syndrome (SS), and 32 age- and sex-matched healthy controls. Cardiac autonomic modulation was quantified via Heart Rate Variability (HRV) analysis using short-term (5-minute) ECG recordings. The dynamic activity of the hypothalamic-pituitary-adrenal (HPA) axis was mapped through the Cortisol Awakening Response (CAR), utilizing salivary samples collected at four precise time points (awakening, +30 min, +60 min, and bedtime) and analyzed via ELISA. To ensure protocol reliability, only samples from participants with verified spontaneous awakening were included. Systemic inflammation was assessed through hemogram parameters and serum C-reactive protein (CRP, mg/dL) levels.

RESULTS

Our data reveal a distinctive neuroendocrine-immune signature in both disorders. Both SLE and SS patients exhibited a significantly blunted CAR at 60 min (p < 0.05), suggesting a failure in the "anticipatory" stress response. Autonomic profiling showed widespread impairment in SDNN and Total Power (p < 0.05) across both groups. Notably, we identified a phenotypic divergence: SLE patients demonstrated a specific impairment in parasympathetic "vagal tone" (RMSSD and HF), whereas SS patients were characterized by a unique leukocyte and neutrophil depletion (p < 0.05). This suggests that while HPA hyporesponsiveness is a shared trait, the autonomic-immune coupling may follow disease-specific pathways.

CONCLUSIONS

This study provides compelling evidence of interrelated regulatory alterations in the neuro-immune axis of SLE and SS patients. The combination of diminished cortisol signaling and impaired vagal modulation creates a "permissive environment" for chronic inflammation. By demonstrating that the degree of HPA suppression correlates with autonomic rigidity, we propose a new theoretical framework: systemic autoimmunity is not merely an immune defect but a dysregulation of the neuroendocrine-autonomic homeostatic loop. Targeting this "stress-axis" could provide a novel bio-behavioral window for therapeutic intervention and disease monitoring.