Mapping Systemic Lupus Erythematosus Heterogeneity at the Single Cell Level

Patients with Systemic Lupus Erythematosus (SLE) display a complex blood transcriptome whose cellular origin is poorly resolved. Using single-cell RNA-seq, we profiled ~276,000 PBMCs from 33 children with SLE (cSLE) with different degrees of disease activity (DA) and 11 matched controls. Increased expression of Interferon-stimulated genes (ISGs) distinguished cSLE from healthy control cells. The high-ISG expression signature (ISGhi) derived from a small number of transcriptionally defined subpopulations within major cell types, including monocytes, CD4+ and CD8+ T cells, NK cells, cDCs, pDCs, B cells and especially plasma cells. Expansion of unique subpopulations enriched in ISGs and/or in monogenic Lupus-associated genes classified patients with the highest DA. Profiling of ~82,000 single PBMCs from adult SLE patients confirmed the expansion of similar subpopulations in patients with the highest DA. This study lays the groundwork for resolving the origin of the SLE transcriptional signatures and the disease heterogeneity towards precision medicine applications. Patient demographics, clinical and laboratory data and treatment are summarized and available. The genomic data for participant aHD2 will not be included in the dataset The study description is reprinted from Nehar-Belaid et. al. Nature Immunology, 2020, with permission from Nature Immunology Group]]>
Inclusion criteria for Pediatric SLE cohort: To be enrolled as an affected, an individual is required to provide consent and have a diagnosis that satisfies the American College of Rheumatology's criteria for the classification SLE, be ≤ 25 years old. Exclusion criteria for Pediatric SLE cohort: Adults over the age of 25 years old Pregnant autoimmune patients who are referred to adult care physicians and not followed in the pediatric rheumatology clinic while pregnant Inclusion criteria for Pediatric healthy cohort: Subjects with no known diagnosis of immune- or inflammatory-mediated disease No vaccine received within 14 days of blood collection; no fever within 14 days of blood collection No seasonal allergies at the time of blood collection No antibiotics, allergy medications or steroidal medications within 14 day of blood collection Subjects must be ≤ 25 years of age Exclusion criteria for Pediatric healthy cohort: Diagnosis of immune- or inflammatory-mediated disease, including seasonal allergies, influenza or common cold Receipt of vaccine within 14 day of blood collection Taking medication for allergies, inflammation, bacterial infection > 25 years of age Pregnant females Inclusion criteria for Adult SLE cohort: Adult SLE would be included in the study if they are a male or female from 18 to 65 years old, provide consent and have an existing diagnosis of lupus for over 12 months Exclusion criteria for the Adult SLE cohort: Autoimmune disease such as: Rheumatoid Arthritis, Inflammatory Bowel Disease HIV, AIDS or other Immunodeficiency Use of steroids (prednisone > 15mg/ day oral) or methotrexate or equivalent Any changes in therapy with Methylprednisolone, Mycophenolic acid, Azathioprine or Methotrexate in the last 30 days Use of biologics within the last 30 days Use of Intramuscular or Intravenous Solumedrol within 30 days of screening Current substance and/or alcohol abuse Pregnancy Prisoners Inclusion criteria for Healthy Adults cohort: Controls would be included in the study if they match cases on the basis of sex, age group and self-identified race and ethnicity groups, provide consent, and have the ability to cooperate with the study Exclusion criteria for Healthy Adults cohort: Autoimmune disease such as SLE, SSC, Rheumatoid Arthritis HIV or AIDS or other immunodeficiency Take any prescribed medication more than 3 times a week for longer than 2 weeks (birth control medication is permitted) Current or prior history of use of anti-inflammatory drugs or steroids (prednisone >15mg/ day oral) or methotrexate or equivalent Current or prior history of treatment with biologics Currently abuse substance and/or alcohol Pregnancy Prisoners ]]>