Analysis Links IFNβ Levels With Severe Lupus Nephritis, Immune Complex Composition in SLE

Patients with higher levels of interferon-β (IFNβ) in their B cells were less likely to have oral and nasal ulcers or photosensitivity.

Interferon-β (IFNβ) levels in the B cells of patients with systemic lupus erythematosus (SLE) appear to be associated with a history of severe lupus nephritis (LN) and glomerular basement membrane (GBM) immune complex (IC) deposition, according to a new study.

IFNβ also correlates with certain anatomical features of chronic glomerular lesions, the report said. The findings were published in Arthritis Research & Therapy.

Corresponding author John D. Mountz, MD, PhD, of the University of Alabama at Birmingham, and colleagues explained that their previous research showed that B cell intracellular IFNβ levels have a strong correlation with the anti-Smith (anti-Sm) antibodies and renal disease. Yet, it was not clear how that impacted the histopathological features of LN.

The investigators analyzed the peripheral blood mononuclear cells (PBMCs) of 80 patients with SLE using flow cytometry, calculating the percentage of IFNβ-positive cells in immunoglobulin D-positive, CD27-negative naive CD19-positive B cells. Sixteen healthy donors were also analyzed. The authors then used 23 biopsy specimens to identify correlations between B cell IFNβ with LN status and histopathological features.

Most of the patients who had their blood samples analyzed were White (55 patients) and female (76 patients). Their mean age at diagnosis was 31 years and their mean age at study enrollment was 41 years. Thirty-three patients in the cohort had LN, and 19 of those patients had proliferative LN that was either isolated or combined with class II or class V. Fifty-four patients had arthritis, 38 had photosensitivity rash, and 32 had oral or nasal ulcers. Fifty-nine patients had active disease at the time of enrollment, and most of those patients (39) had mild disease activity, as rated by the SLE Disease Activity Index (SLEDAI), the authors reported.

The analysis showed that B cell IFNβ was linked with anti-Sm and anti-DNA antibodies, as well as LN, but it was negatively associated with oral and nasal ulcers and photosensitivity. They found that patients with B cell IFNβ were more likely to have IC deposits in the GMB, but not in the mesangial or tubular regions.

“The present findings suggest that B cell IFNβ may be one factor underlying the development of anti-Sm which in turn leads to renal disease by forming IC, direct binding to Sm or other autoantigens in the kidney, as previously proposed,” Mountz and colleagues wrote.

IFNβ levels also affected the risk of certain classes of LN.

“Patients with high B cell IFNβ had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B cell IFNβ (p < 0.0001),” the authors wrote.

In histopathological terms, the investigators said they found that B cell IFNβ positivity was linked with active glomerular lesions determined by fibrocellular crescents, chronic glomerular lesions indicated by segmental sclerosis, and a spike/hole membranous pattern of renal damage.

“These results provide insights into the pathogenic mechanisms of B cell IFNβ concerning the production of autoAbs, immune complexes, and renal disease tissue damage that can help guide future therapies that target type I IFN for the treatment of SLE,” Mountz and colleagues concluded.

Reference

Alduraibi F, Fatima H, Hamilton JA, Chatham WW, Hsu HC, Mountz JD. Lupus nephritis correlates with B cell interferon-β, anti-Smith, and anti-DNA: a retrospective study. Arthritis Res Ther. Published online April 18, 2022. doi:10.1186/s13075-022-02766-1