Lupus Omics Cutaneous Kidney Investigative Team (LOCKIT) - Pain Supplement

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Clinical pain phenotypes and mechanisms in rheumatic diseases are poorly understood. The Accelerating Medicines Partnership Autoimmune and Immune-Mediated Disease (AMP AIM) Program addresses common themes across autoimmune diseases, and delineating the complexity and impact of pain and the dissociation between patient and physician perceived disease burden not necessarily related to untreated inflammation is a major unmet need. Pain phenotypes such as nociceptive (tissue injury), nociplastic (central sensitization), and neuropathic pain and their contribution to therapeutic non-response constitutes a critical knowledge gap. Pain is a core domain affecting quality of life from the perspective of patients with Systemic Lupus Erythematosus (SLE), Psoriatic Spectrum Disorder (PSD), Rheumatoid Arthritis (RA) and Sjögren’s Disease (SjD). This supplement will utilize skin biopsies acquired by the SLE and PSD disease teams in those with cutaneous disease to identify novel pain biomarkers. Patients with lupus nephritis and SjD will be included given the importance of pain in these patients as well and to provide further comparative insights. Governance will be under the leadership of Jill Buyon (mPI SLE) and Alexis Ogdie (mPI PSD) with collaboration provided by other members of the respective disease teams and consultation by Yvonne Lee bringing expertise in pain phenotyping. In parallel, efforts will be harmonized in RA and PSD with a focus on synovial biopsies. Two specific aims are proposed. In Aim 1, pain phenotypes will be delineated in patients with SLE, PSD, and SjD. In addition to the PROMIS 29 measures, patients consecutively enrolled will complete the 2016 Fibromyalgia (FM) Survey Criteria and pain catastrophizing scale. Over 2 years, the SLE team will enroll patients with active skin disease (N=20) and/or new onset nephritis (N=40), the PSD team will enroll patients with psoriasis and/or PSA (N=30), and patients with varying clinical and/or laboratory characteristics consistent with SjD (N=20) will be recruited by this third team. In Aim 2, differences in skin biomarkers and functional brain MRI among patients with SLE, PSD, and SjD with and without concomitant FM or pain sensitization will be assessed. This aim leverages studies planned to investigate lesional and non-lesional skin from patients with cutaneous LE and PSD to test the hypothesis that local nerves play a role in pain sensitization and itch. Following baseline surveys, a subset of patients with skin biopsies with differing pain phenotypes will undergo functional brain imaging. With systematic collection of deeply phenotyped patients and extensive omics derived from tissue as a part of AMP AIM, substantial innovations in pain research are expected.