Purpose Longitudinal studies specifically addressed to describe the development of systemic autoimmune diseases in anti-phospholipid (aPL) positive healthy subjects are not available. Thus, we longitudinally followed a single-center aPL carriers cohort to evaluate the rate of disease evolution, focusing on anti-phospholipid syndrome (APS) and Systemic Lupus Erythematosus (SLE).
Methods Healthy subjects positive for aPL in at least two consecutive determinations were enrolled. Medical history was recorded and laboratory evaluation was performed [aCL and anti-β2GPI IgG/IgM, lupus anticoagulant (LA), antinuclear antibody (ANA), C3/C4 levels, genetic thrombophilia screening]. All subjects were evaluated every six months to register the occurrence of clinical and laboratory features suggestive of APS or SLE.
Results Ninety-five subjects (M/F 20/75, median age at first determination 46 years, IQR 19) were enrolled; aCL were identified in 75 carriers (78.9%), aβ2GPI in 60 (62.5%) and LA in 45 (47.3%). We prospectively followed our cohort for a median period of 72 months (IQR 84). In detail, eight aPL carriers (8.4%) were lost to follow up. At the last visit, 6 (6.3%) subjects became persistently negative after a median interval of 21 months (IQR 43.5); all of them were female with aCL positivity at low titer in 83.3% of cases. During a total follow-up of 7692 person-months, we found an absolute risk for systemic autoimmune diseases development equal to 0.9%. In detail, four patients (4.2%) developed a thrombotic event and were classified as affected by APS. Notably, all of these subjects shared a laboratory phenotype, characterized by LA and ANA positivity. Interestingly, this phenotype was observed only in two out of the remaining persistently positive carriers (2.7%, p= 0.0001). Furthermore, three patients could be classified as affected by SLE according to the 2019 ACR/EULAR classification criteria. All these patients were then treated by HCQ 5 mg/Kg/daily.
Conclusions In the present study, we evaluated the progression from asymptomatic aPL positivity condition to clinically manifested autoimmune disease. The tight and prolonged monitoring of our cohort allowed to observe the evolution to APS or SLE in almost 7% of cases. To the best of our knowledge, this is the first longitudinal cohort study specifically addressing the transition to systemic autoimmune diseases in aPL positive healthy individuals. Of note, it should be considered not only the expected APS development, but also the progression to SLE.
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