title: Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nucleic acids and highly diverse clinical manifestations. To assess its molecular heterogeneity, we longitudinally profiled the blood transcriptome of 158 pediatric patients. Using mixed models accounting for repeated measurements, demographics, treatment, disease activity (DA), and nephritis class, we confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of DA. We detected gradual enrichment of neutrophil transcripts during progression to active nephritis and distinct signatures in response to treatment in different nephritis subclasses. Importantly, personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials. This approach may improve trial design and implementation of tailored therapies in genetically and clinically complex autoimmune diseases. PAPERCLIP.
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Banchereau
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Hong
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Brandi
authors.initials: B
authors.lastname: Cantarel
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Baldwin
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Jeanine
authors.initials: J
authors.lastname: Baisch
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Edens
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Alma-Martina
authors.initials: AM
authors.lastname: Cepika
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Acs
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Turner
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Anguiano
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Vinod
authors.affiliation: UT Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Kahn
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Obermoser
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Blankenship
authors.affiliation: UT Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Wakeland
authors.affiliation: UT Southwestern Medical Center, Dallas, TX 75235, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA.
authors.forename: Lorien
authors.initials: L
authors.lastname: Nassi
authors.affiliation: UT Southwestern Medical Center, Dallas, TX 75235, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA; Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Alisa
authors.initials: A
authors.lastname: Gotte
authors.affiliation: UT Southwestern Medical Center, Dallas, TX 75235, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA.
authors.forename: Marilynn
authors.initials: M
authors.lastname: Punaro
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA; MedImmune, Gaithersburg, MD 20878, USA.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Rossello-Urgell
authors.affiliation: UT Southwestern Medical Center, Dallas, TX 75235, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA.
authors.forename: Tracey
authors.initials: T
authors.lastname: Wright
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA. Electronic address: virginia.pascual@bswhealth.org.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D059467:Transcriptome