Background Early diagnosis of lupus nephritis (LN) can be challenging since some patients do not exhibit overt clinical manifestations until advanced stages. B cell interferon-beta (IFNβ) correlates with development of B cell autoreactive phenotype. The objective of the present study is to determine if elevated IFNβ in circulating B cells can be a useful indicator for the development of more severe histopathologic features of LN.
Methods Flow cytometry was used to quantitate intracellular IFNβ in naive (IgD+CD27−) CD19+ B-cells in the peripheral blood mononuclear cells (PBMCs) of a cross-sectional cohort (N=80) of patients with systemic lupus erythematosus (SLE), 33 of whom had lupus nephritis. Serologic and clinical manifestations of LN included anti-DNA, anti-Sm, C3, C4, and urine protein/creatinine ratio were determined. The correlation of B-cell IFNβ with lupus nephritis classification and histopathological findings, light, electron microscopy, and immunofluorescence (IF) for deposition of IgM, IgG, IgA, C1q, and C3 was determined in 23 of the 33 patients for whom renal biopsy data was available.
Results LN was identified in 41% of our cohort of 80 SLE patients. Naïve B-cell IFNβ was positively associated with the development of LN but not cutaneous disease. Higher levels of B-cell IFNβ also correlated with higher levels of circulating anti-dsDNA, anti-Sm, and the urinary protein/creatinine ratio. Biopsy examination revealed that proliferative LN lesions (Class III, IV with or without V) characterized by significantly elevated endocapillary hypercellularity, fibrous crescent, and fibrocellular crescent were significantly associated with high B-cell IFNβ. Surprisingly, IgG, IgA, IgM, C3, and C1q deposition in the kidney was not correlated with B-cell IFNβ.
Conclusions Our results suggest that B-cell IFNβ can be used in combination with other clinical diagnostic markers to assist in identifying patients who are at high risk of developing advanced LN.
Acknowledgments This work was supported by the VA Merit Review grant [I01BX004049]; the NIH grants [R01-AI-071110, R01 AI134023], the Lupus Research Alliance Distinguished Innovator Award; the LRA Target Identification in Lupus Award; and to support flow cytometry analysis [P30-AR-048311 and P30-AI-027767]. Funders had no role in design, analysis, and reporting.
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