Caveolin 1 Is a Reliable Biomarker of Endothelial Damage in the More Aggressive Subset of Antiphospholipid Syndrome Nephropathy

Background: Thrombotic microangiopathy (TMA) as seen in antiphospholipid syndrome nephropathy (APSN) is associated with poor renal outcomes, yet reliable biomarkers for its identification remain limited. Caveolin-1 (Cav-1) has emerged as a potential marker of endothelial damage and microvascular injury. This study investigates the diagnostic potential value of Cav-1 immunohistochemistry (IHC) in APSN-related TMA. Methods: Patients were retrieved from the Piedmont and Aosta Valley Rare Disease Registry, from which a total of 771 APS cases had been recorded. Only case with biopsy-proven renal involvement were included. Cases were classified into three histopathological clusters: TMA (APSN-TMA), hyperplastic vasculopathy, and subendothelial oedema. Immunohistochemical staining for Cav-1 was performed and graded based on expression in peritubular and glomerular capillaries. Clinical and laboratory data, including antiphospholipid antibodies (aPL) profile, were correlated with Cav-1 expression Results: Out of 771 patients with APS, a total of 11 patients with primary APS and renal involvement were retrieved (1,43%). APSN-TMA was identified in 7 (63.3%) cases, hyperplastic vasculopathy in 2 (18.1%), and subendothelial oedema in 2 (18.1%). Cav-1 expression was significantly higher in APSN-TMA cases in both glomerular (p=0.00091) and peritubular (p=0.047) compared to other clusters, with 5 of 7 APSN-TMA cases exhibiting diffuse (grade III) staining. Triple aPL postive testing was more prevalent in APSN-TMA cases, reinforcing their distinct pathophysiological profile. Conclusion: APSN-TMA is a rare manifestation of a rare disease. Cav-1 is strongly associated with APSN-TMA and may serve as a novel marker for its diagnosis and stratification. Given the poor renal prognosis of APSN-TMA, identifying affected patients is crucial for optimizing management strategies. While these findings support Cav-1 as a promising diagnostic tool, further studies in larger cohorts are needed to validate its clinical utility and distinguish APSN-TMA from other forms of TMA. Future therapeutic implications, including eligibility for adjunctive immunomodulatory therapies, warrant further exploration.