Elizabeth Arkema

Sarcoidosis is an inflammatory disease in which granulomas form in any part of the body, most often affecting the lungs and lymph nodes. The disease varies among patients in terms of onset, severity and prognosis. A major obstacle in identifying causes of sarcoidosis is the inability to distinguish between different groups of patients. Inflammatory biomarker levels in combination with genetics can be used to better characterize and treat patients.My goal is to identify subgroups of sarcoidosis patients using genetic and proteomic data and determine whether these are associated with sarcoidosis prognosis. I will achieve this goal by collecting proteogenomic data from several sources of cases and controls. First, I will examine the relationship between genetics and inflammatory proteins in sarcoidosis patients. Then I will investigate whether there are clusters of patients with similar characteristics (endotypes) using a data-driven approach. To determine whether these subgroups are clinically meaningful, we will examine whether the risk of poor prognosis is different between the endotypes.The proposed project will be the first of its kind and will reveal important mechanisms of sarcoidosis pathogenesis. The use of genetics and proteomics from pre-clinical and newly diagnosed patients will be used to set the foundation for developing non-invasive biomarkers for diagnosis and endotype-specific treatment of sarcoidosis.

SLE is a heterogeneous autoimmune disease, characterized by the production of autoantibodies. Vascular disease (VD) is a major cause of early morbidity and mortality. Based on clinical experience and unsupervised clustering of 13 clinically relevant autoantibodies in 911 patients, we identified 4 SLE subgroups. Roughly outlined below:Anti-SSA/SSB, skin manifestations, Sjogren’s syndrom, HLA-DRB1*03Anti- dsDNA/nucleosome/Sm, nephritis, enhanced atherosclerosis, early onset, HLA-DRB1*15aPL, clotting disorders, HLA-DRB1*04No autoantibodies, late onset, no HLA association.Aim: To identify mechanisms contributing to autoimmunity and VD, by analyses of the 4 SLE subgroups separately.Method: We have since 1995 followed well-characterized cohorts, comprising &gt

800 SLE, and 320 controls, every 10 years. Follow-up is ongoing at the clinic and in the National Patient Registries (NPR), where we also identify all Swedish SLE patients (N=7000) and 10 controls/patient.We seek to determine if the 4 groups differ regarding:Proteomics, new autoantibodies and microparticles (vesicles of cellular origin).Blood samples drawn during the different menstrual phases in women with SLE (new approach).Vascular function in the heart, as determined by cardiac magnetic resonance investigation.VD and long-term outcomes in NPRSignificance: Our results can impact how we diagnose and treat SLE in the future. VD mainly affects groups 2 and 3 but by different mechanisms, calling for tailored preventive treatment.

Sarcoidosis is an inflammatory disease that primarily affects the lungs, but other organs can also be affected. Sweden has the highest incidence of sarcoid in the world with 1100 new diagnoses per year. The disease has a significant negative impact on the quality of life and reduces life expectancy. Previous research suggests that sarcoid is linked to cancer because they share a defective immune system. Sarcoidosis patients are more often affected by cancer, moreover, sarcoidosis usually occurs after treatment in cancer patients. Knowledge of a link between sarcoid and cancer is limited because it is difficult to explore two diseases that are challenging to diagnose. We will combine large data sets from health data and quality registries with more detailed information from patient records. We will apply epidemiological methods to investigate whether sarcoid patients develop malignancy more frequently than the general population. In addition, we will investigate whether cancer patients are more often affected by sarcoid and whether the treatment affects the risk of developing sarcoid. Clinical information will be examined in detail from patients with both sarcoid and malignancy to validate the diagnoses with the goal of reducing misclassifications of sarcoid and malignancy, respectively, in the future. Our results will lead to new fundamental knowledge. This knowledge is necessary to improve our strategy for diagnosing and treating both sarcoid and cancer. Our research will lead to better understanding of how sarcoid and malignancy are related to each other. We want to identify factors that make it easier to distinguish between malignancy and sarcoid, so that unnecessary treatments and tests can be avoided.