AIM for RA:
The AMP AIM-for-RA projects’ overarching goals are to define how synovial tissue variation and cellular crosstalk mechanisms inform disease onset, disease trajectory, personalized treatment approaches, and the development of new, rational drug targets. This project will first focus on new onset disease with recruitment of 50 treatment-naïve RA patients across 9 academic institutions and analysis of synovial tissue, peripheral blood, host, and environmental factors (e.g., microbial) to identify pathophysiologic mechanisms and environmental triggers associated with disease onset (cohort 1). We will leverage this early disease cohort to compare the key cellular interactions and pathways in RA target tissue to other autoimmune and immune mediated diseases. AIM-for-RA will then define the cellular and molecular signatures of remission and treatment response in these patients followed longitudinally with clinical outcomes and repeat biopsies. A second phase will delineate the synovial cell signatures and networks that predict targeted biologic treatment responses in methotrexate inadequate responders (cohort 2). Overall, these studies will help identify new disease targets, guide prognosis, and lay the groundwork for precision medicine strategies in RA.
Psoriatic Spectrum Disease – ELucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium (ELLIPSS)
ELLIPSS’ overall goal is to identify the key immune and effector cells in the skin, joints, peripheral blood and entheses that promote specific phenotypes within Psoriasis (PsO) and psoriatic arthritis (PsA). ELLIPSS aims to define the cellular and molecular signatures of remission and treatment response in longitudinal PsO and PsA cohorts. In these cohorts, derived from over 10 academic institutions with advanced expertise in the field, ELLIPSS will also characterize the host, environmental (e.g., microbial), and other factors that contribute to the transition from PsO to PsA.
ELLIPSS will enroll up to 155 unique PsO subjects, 190 unique PsA subjects, and 150 unique participants that transition from PsO to PsA. In effort to avoid the effects of treatment as confounders for disease de- and re-construction, ELLIPSS will include at least 50% of subjects with systemic treatment-naïve psoriasis, defined as any adult patient with active psoriasis who has not been treated with oral systemic or biologic therapies.
Sjögren’s Team for Accelerating Medicines Partnership (STAMP)
STAMP aims to broaden the understanding of the phenotypic and molecular heterogeneity of Sjögren’s disease (SjD). STAMP plans to determine disease mechanisms inherent to progression from non-SjD to SjD, and from early to advanced SjD. STAMP also wants to determine those disease mechanisms and molecular overlap between SjD and systemic lupus erythematosus (SLE) and identify therapeutic targets to stabilize early disease and reverse/improve advanced. STAMP will utilize a molecular deconstruction-reconstruction model and the “Scale-up Phase” approach to identify therapeutic pathways and new biomarkers enabling earlier diagnosis of SjD.
STAMP will enroll new participants with signs and symptoms suggestive of SjD and a follow-up study of participants who were enrolled in either SICCA or OMRF cohorts 10 to 15 years earlier. Among new participants, a subset will meet SjD criteria without another systemic autoimmune rheumatic diseases (SARDs), a subset will meet SjD criteria and either SLE or RA criteria, and a subset will not meet SjD criteria or meet them partially and serve as symptomatic controls. Additionally, they will recruit healthy controls whose biospecimens are critical in the molecular deconstruction/reconstruction model context.
Lupus Omics Cutaneous Kidney Investigative Team (LOCKIT)
LOCKIT aims to identify patients with immune-mediated kidney injury using non-invasive biomarkers of incipient Lupus nephritis (LN). Identification of these patients will aid in development of early treatment, which is expected to improve complete renal response rates and attenuate damage accrual by limiting the duration of intra-renal inflammation. Additionally, LOCKIT aims to characterize pathogenic mechanisms activated in the kidneys of these patients, with the overall goal of providing clues to the initial triggers of LN.
LOCKIT aims to address these issues through comparisons of well-characterized clinical groups to identify biomarkers that stratify patients with low-grade proteinuria, who would not generally be considered for therapy, into those with actionable LN and those without LN. These patients will be used to characterize the molecular pathways operative in the kidney during incipient LN and the transition from no LN to clinical (i.e., proteinuria >0.5 g/d) LN. Secondary goals will be to describe the natural history of SLE patients with low-grade proteinuria and determine any differences in urine sediment, proteinuria, and kidney function after one year of follow-up between patients who never required LN therapy, patients who were started on LN therapy early LN, and patients who were started on LN therapy late for clinical LN.
In a second project, LOCKIT aims to determine the molecular pathology/pathogenesis of non-response. This information will be applied to future LN trials to help patients that require therapies beyond SOC. With this, LOCKIT expects this will increase the chances of successfully finding combinations of targeted therapies to increase overall CRR rate. Additional studies on uncovering molecular basis of renal non-response to SOC will inform identification of non-tissue-based biomarkers of non-response in blood or urine.