Lupus nephritis correlates with B cell interferon-[beta], anti-Smith, and anti-DNA: a retrospective study

• Published in: Arthritis research & therapy 2022-04, Vol.24 (1)
• Main Authors: Alduraibi, Fatima, Fatima, Huma, Hamilton, Jennie A, Chatham, W. Winn, Hsu, Hui-Chen, Mountz, John D
• Format: Article
• Language: English
• Subjects: Drug therapy; Genetic aspects; Interferon; Lupus; Nephritis; Patient outcomes
• ISSN: 1478-6354
• DOI: 10.1186/s13075-022-02766-1

Background In systemic lupus erythematosus (SLE), detection of interferon-[beta] (IFN[beta]) in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFN[beta] in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN). Methods The percentage of IFN[beta].sup.+ cells in IgD.sup.+CD27.sup.- naïve CD19.sup.+ B cells (B cell IFN[beta]) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B cell IFN[beta] with LN classification and with histopathological findings (light, electron, and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens. Results B cell IFN[beta] is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.013), and LN (p < 0.001) but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B cell IFN[beta] positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B cell IFN[beta] had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B cell IFN[beta] (p < 0.0001). Histopathological features positively associated with increased B cell IFN[beta] included active glomerular lesions as determined by fibrocellular crescents (p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015). Conclusion B cell IFN[beta] correlates with history of severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions. Keywords: Systemic lupus erythematosus, Lupus nephritis, B cell interferon beta, Autoantibodies