Clinical and laboratory characteristics of early-onset and delayed-onset lupus nephritis patients: A single-center retrospective study.

BACKGROUND: Lupus nephritis (LN) manifests systemic lupus erythematosus (SLE) and is characterized by various clinical and laboratory features. This study aimed to comprehensively evaluate the characteristics of LN patients according to the time of LN diagnosis: early-onset (LN diagnosed within one year from SLE diagnosis) vs. delayed-onset (LN diagnosed more than one year after SLE diagnosis). METHODS: We conducted a retrospective analysis of medical records from all SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected data on demographic, clinical, and laboratory characteristics, including histological findings, treatment modalities, and disease outcomes. Statistical analyses were performed to identify factors impacting LN development and prognosis. RESULTS: Among 331 LN patients, early-onset was diagnosed in 207 (62.54%) and delayed-onset was documented in 122 cases (36.86%). In 2 (0.6%) LN cases, the time of first kidney manifestation in the SLE course was unknown. Delayed-onset LN had a higher female-to-male ratio and younger age at SLE diagnosis. This group was associated with more severe clinical manifestations. In turn, studied subgroups did not differ in internist comorbidities, kidney histopathology, and family history regarding autoimmune diseases. Delayed-onset LN exhibited a higher frequency of anti-dsDNA, anti-Smith, anti-Ro, anti-RNP, and anti-cardiolipin IgG autoantibodies. During a 14-year follow-up period, 16 patients died. Mortality rate and causes of death were comparable in both analyzed subgroups. CONCLUSIONS: More severe clinical manifestations in delayed-onset LN prompt strict monitoring of non-LN SLE patients to diagnose and treat kidney involvement early. Also, recognizing the higher frequency of autoantibodies such as anti-dsDNA or anti-Smith in delayed-onset LN underscores the potential value of autoantibody profiling as a diagnostic and prognostic tool.

Co-Expression Analysis of Airway Epithelial Transcriptome in Asthma Patients with Eosinophilic vs. Non-Eosinophilic Airway Infiltration.

Asthma heterogeneity complicates the search for targeted treatment against airway inflammation and remodeling. We sought to investigate relations between eosinophilic inflammation, a phenotypic feature frequent in severe asthma, bronchial epithelial transcriptome, and functional and structural measures of airway remodeling. We compared epithelial gene expression, spirometry, airway cross-sectional geometry (computed tomography), reticular basement membrane thickness (histology), and blood and bronchoalveolar lavage (BAL) cytokines of n = 40 moderate to severe eosinophilic (EA) and non-eosinophilic asthma (NEA) patients distinguished by BAL eosinophilia. EA patients showed a similar extent of airway remodeling as NEA but had an increased expression of genes involved in the immune response and inflammation (e.g., KIR3DS1), reactive oxygen species generation (GYS2, ATPIF1), cell activation and proliferation (ANK3), cargo transporting (RAB4B, CPLX2), and tissue remodeling (FBLN1, SOX14, GSN), and a lower expression of genes involved in epithelial integrity (e.g., GJB1) and histone acetylation (SIN3A). Genes co-expressed in EA were involved in antiviral responses (e.g., ATP1B1), cell migration (EPS8L1, STOML3), cell adhesion (RAPH1), epithelial-mesenchymal transition (ASB3), and airway hyperreactivity and remodeling (FBN3, RECK), and several were linked to asthma in genome- (e.g., MRPL14, ASB3) or epigenome-wide association studies (CLC, GPI, SSCRB4, STRN4). Signaling pathways inferred from the co-expression pattern were associated with airway remodeling (e.g., TGF-ß/Smad2/3, E2F/Rb, and Wnt/ß-catenin).