Premature, accelerated onset of atherothrombotic disease is prevalent in patients with systemic lupus erythematosus (SLE). Most, if not all, atherothrombotic diseases are likely to involve platelets and complement. Previously, we discovered that platelets bearing complement activation product C4d (P-C4d) are present in SLE patients, and are significantly associated with antiphospholipid (aPL) antibody positivity and stroke in SLE patients. The goal of the present study was to further elucidate the role of aPL and other platelet-reactive autoantibodies in the generation of P-C4d. To determine the association between P-C4d and aPL antibodies, the serum levels of aPL antibodies and P-C4d of 180 SLE patients were measured by enzyme-linked immunoassays and flow cytometry, respectively. To investigate the role of aPL antibodies, and possibly other autoantibodies as well, in mediating the generation of P-C4d, in vitro 2-step P-C4d induction experiments were performed. The results showed that the presence and levels of aPL antibodies in the serum were specifically elevated in SLE patients with positive P-C4d. The plasma and immunoglobulins purified from SLE patients who were positive for P-C4d and aPL were capable of inducing C4d deposition on normal platelets in vitro. The capacity of SLE plasma in inducing P-C4d appeared to correlate proportionately to the serum aPL levels. Collectively, the results demonstrate that both aPL and other platelet-reactive autoantibodies may participate in mediating the generation of P-C4d in SLE patients.
Background The prevalence of diabetes in the state of West Virginia (WV) is amongst the highest in the United States, making diabetic retinopathy (DR) and diabetic macular edema (DME) a major epidemiological concern within the state. Several challenges exist regarding access to eye care specialists for DR screening in this rural population. A statewide teleophthalmology program has been implemented. We analyzed real-world data acquired via these systems to explore the concordance between image findings and subsequent comprehensive eye exams and explore the impact of age on image gradeability and patient distance from the West Virginia University (WVU) Eye Institute on follow-up. Methods Nonmydriatic fundus images of diabetic eyes acquired at primary care clinics throughout WV were reviewed by retina specialists at the WVU Eye Institute. Analysis included the concordance between image interpretations and dilated examination findings, hemoglobin A1c (HbA1c) levels and DR presence, image gradeability and patient age, and distance from the WVU Eye Institute and follow-up compliance. Results From the 5,512 fundus images attempted, we found that 4,267 (77.41%) were deemed gradable. Out of the 289 patients whose image results suggested DR, 152 patients (52.6%) followed up with comprehensive eye exams—finding 101 of these patients to truly have DR/DME and allowing us to determine a positive predictive value of 66.4%. Patients within the HbA1c range of 9.1-14.0% demonstrated significantly greater prevalence of DR/DME (p < 0.01). We also found a statistically significant decrease in image gradeability with increased age. When considering distance from the WVU Eye Institute, it was found that patients who resided within 25 miles demonstrated significantly greater compliance to follow-up (60% versus 43%, p < 0.01). Conclusions The statewide implementation of a telemedicine program intended to tackle the growing burden of DR in WV appears to successfully bring concerning patient cases to the forefront of provider attention. Teleophthalmology addresses the unique rural challenges of WV, but there is suboptimal compliance to essential follow-up with comprehensive eye exams. Obstacles remain to be addressed if these systems are to effectively improve outcomes in DR/DME patients and diabetic patients at risk of developing these sight-threatening pathologies.
Premature and accelerated onset of atherothrombotic disease is prevalent in patients with SLE. Most, if not all, atherothrombotic diseases are likely to involve platelets and the complement system in some capacity. Previously, we discovered that platelets bearing complement activation product C4d (P-C4d) are present in approximately 20% of SLE patients and are significantly associated with anti-phospholipid (aPL) antibody positivity and stroke in SLE patients. The goal of the present study was to elucidate the role of aPL and other platelet-reactive autoantibodies in the generation of P-C4d. To determine the association between P-C4d and aPL, the level of P-C4d in 180 SLE patients was measured by flow cytometry. Serum level of aPL, including anti-cardiolipin (aCL) and anti-b2 glycoprotein I (anti-b2GPI) antibodies, in these patients was measured by enzyme-linked immunosorbent assays. To investigate the role of aPL, and possibly other autoantibodies as well, in mediating the generation of P-C4d, in vitro 2-step transfer experiments using normal platelets in combination with plasma or immunoglobulin derived from SLE patients were performed. The results showed that the presence and levels of serum aCL and anti- anti-b2GPI were highly specific for SLE patients with positive P-C4d. The plasma and immunoglobulins purified from SLE patients who were positive for P-C4d and aCL/anti-b2GPI were able to induce C4d deposition on normal platelets in vitro. The capacity of SLE plasma in inducing P-C4d appeared to correlate proportionately to the serum aCL levels. Collectively, the results demonstrate that both aPL, particularly aCL, and other platelet-reactive autoantibodies participate in mediating the generation of P-C4d in SLE patients.
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