Caveolin-1 as a Marker of Endothelial Damage in Primary Antiphospholipid Syndrome Nephropathy

Rationale & Objective: Thrombotic microangiopathy (TMA) as seen in antiphospholipid syndrome nephropathy (APSN) is associated with poor kidney outcomes. Caveolin-1 (Cav-1) has emerged as a potential marker of endothelial damage and microvascular injury. Study Design: This retrospective study investigates the diagnostic potential value of Cav-1 immunohistochemistry in APSN-related TMA. Setting & Participants: Patients were retrieved from the Piedmont and Aosta Valley Rare Disease Registry, from which a total of 771 APS cases had been recorded. Exposure: Only case with biopsy-proven renal involvement were included. Outcomes: Cases were classified into three histopathological clusters: TMA (APSN-TMA), hyperplastic vasculopathy, and subendothelial edema. Immunohistochemical staining for Cav-1 was performed and graded based on expression in peritubular and glomerular capillaries. Analytical Approach: Clinical and laboratory data, including antiphospholipid antibody profiles, 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 edema in 2 (18.1%). Cav-1 expression was significantly higher in APSN-TMA cases in both glomerular (P < 0.001) and peritubular (P < 0.05) capillaries compared with other clusters, with 5 of 7 APSN-TMA cases exhibiting diffuse (grade III) staining. Triple antiphospholipid antibody positive testing was more prevalent in APSN-TMA cases, reinforcing their distinct pathophysiological profile. Limitations: The small sample size warrants validation in larger cohorts, and Cav-1 expression, although associated with APSN, might not be disease-specific. Conclusions: 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. Plain-Language Summary: Antiphospholipid syndrome (APS) is an autoimmune condition that can cause blood clots in many organs, including the kidneys. In some patients, a type of severe small-vessel injury called thrombotic microangiopathy develops, leading to poor kidney outcomes. Diagnosing this form of kidney damage can be challenging. In our study, we examined kidney tissue from people with APS using a special stain for a protein called Caveolin-1, which is found in damaged blood vessel cells. We found that high Caveolin-1 levels were strongly linked to the most aggressive form of APS-related kidney injury. This marker could help doctors identify high-risk patients earlier, improve treatment decisions, and bring more clarity to the complex and varied ways APS can affect the kidneys.