Understanding lymphoid tissue immunology in human SLE and the impact of therapeutic interventions

The National Institute of Allergy and Infectious Diseases awarded La Jolla Institute for Immunology $929,095 on June 2, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to characterize immune cell populations in lymphoid tissue from systemic lupus erythematosus patients and healthy controls using minimally invasive nasal swab sampling combined with flow cytometry and transcriptomic profiling.

The research addresses gaps in understanding tissue-specific immune mechanisms in SLE pathogenesis and treatment response by moving beyond peripheral blood analysis to direct study of immune cells in lymphoid tissue. The team will identify features that correlate with disease activity over time and assess pre- and post-treatment immune responses. The minimally invasive nasal swab protocol enables repeated longitudinal measurements that provide kinetic insights into SLE immunopathology with high-dimensional immunologic resolution.

Work is performed in La Jolla, California, with a period of performance from June 2, 2026, through May 31, 2031.

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by self-reactive antibodies (autoantibodies), and this chronic disease results in significant loss of quality of life and irreversible tissue damage that can result in organ failure and death. With SLE being a disease that affects many organs with a range of severity, newer targeted therapies are needed. Despite advances in understanding SLE, most human studies have relied on peripheral blood, limiting insights into the lymphoid tissue compartments which are likely to be the primary sites where autoreactive t and b cells are activate. As a result, major gaps remain in our understanding of tissue-specific immune mechanisms in SLE pathogenesis and treatment response. To address these knowledge gaps, we propose a novel approach using minimally invasive nasal swab lymphoid tissue sampling combined with high-dimensional immunologic analysis in SLE. Unlike blood-based testing, this method enables direct study of immune cells in a lymphoid tissue. Our team has developed and validated a safe and reproducible nasal swab protocol, paired with flow cytometry and transcriptomic profiling, to measure lymphoid tissue immune cell populations with high resolution. This method allows direct interrogation of immune responses in lymphoid tissue over time, which will be a key advance for SLE research. Importantly, such measurements can be done repeatedly, longitudinally over time, allowing for novel kinetic insights into SLE pathophysiology. This approach, combined with our human immunology expertise, can potentially provide unprecedented insights into SLE immune events. We will (1) characterize immune cell populations in lymphoid tissue from SLE patients VS. Healthy controls; (2) identify features that correlate with disease activity over time; and (3) assess pre- and post-treatment immune dynamics in patients receiving common and new SLE therapies. Our central hypothesis is that longitudinal analysis of lymphoid tissue immune signatures will uncover critical drivers of SLE pathogenesis and treatment response. Additionally, we aim to identify key features of these t and b cells that could serve as targets for novel therapeutic interventions and/or biomarkers of disease activity and responses to treatment, thus potentially identify novel SLE therapeutic interventions and biomarkers. The project is entirely focused on human immunology in SLE patients, directly examining lymphoid tissue. Furthermore, we will, for the first time, collect detailed longitudinal data from lymphoid tissues from SLE patients, including patients receiving therapies. By advancing understanding of human adaptive immunity in lupus, this work could significantly improve patient stratification and treatment outcomes in SLE.