Session Type: Poster Session D
Session Time: 8:30AM-10:30AM
Background/Purpose: Our laboratory previously demonstrated a strong association of B cell intracellular interferon beta (IFNβ) with the development of anti-Smith/ribonuclear protein (Sm/RNP), anti-DNA, and lupus nephritis (LN) in African American (AA) systemic lupus erythematosus (SLE) patients. The objective of the present study is to determine if B cell IFNβ can be a unique SLE clinical prognostic marker and if specific histopathologic features of LN can be identified in patients with elevated B cell IFNβ.
Methods: All patients (N=80) met American College of Rheumatology (ACR) 1997 revised SLE criteria, ACR/EULAR classification criteria of SLE or Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were recruited. Demographic, clinical data, and serologic manifestations included creatinine, urine protein/creatinine ratio, anti-DNA, anti-Sm, C3, and C4 were included. Intracellular IFNβ in naïve B cells was analyzed using high dimensional flow cytometry analysis. Isotype specific (IgG and IgM) anti-Sm/RNP and anti-DNA were measured using a standard ELISA method. LN class was defined based on the revised ISN/RPS (2004) criteria and included renal histopathology findings on light, electron microscopy, and immunofluorescence (IF) for IgM, IgG, IgA, C1q, and C3 staining (N=23).
Results: The most common manifestations were arthritis in 68% (n=54), photosensitivity rash in 47% (n=38), LN in 41% (n=33), and oral ulcer in 40% (n=32) of SLE patients. There was a significant positive correlation between naïve B cell IFNβ with race (AA > European American) and LN class (P=0.006, P< 0.0001, respectively). Naïve B cell IFNβ is negatively correlated with photosensitivity (P=0.0451) and oral/nasal ulcer (P=0.0031), and it did not correlate with other symptoms of SLE. Patients with elevated serum anti-Sm (P=0.032 by history; P=0.01 at the time enrollment) and anti-DNA (P=0.013 at the time enrollment) exhibited significantly higher naïve B cell IFNβ. Further, SLE patients with a higher percentage of intracellular IFNβ in naïve B cells also showed a higher serum C3 (P=0.005) and a lower circulating protein/creatinine ratio (P=0.065). Unsupervised ClustVis analysis was used to cluster histologic features associated with B cell intracellular IFNβ into two groups (Fig. 1). LN group 1 (n=13) exhibited low activity (1.8±3.9, p=0.0018) and chronicity index (1.5±0.8, p=0.072) with a lower naïve B cell intracellular IFNβ (46±29%, p=0.0041) compere to LN group 2 (n=10) with high activity (5.9±3.8) and chronicity index (3.0±2.1) with a higher naïve B cell intracellular IFNβ (82±20%) (Fig. 1). There was a lower incidence of wire loop lesions (p=0.0944), fibrocellular crescents (p=0.0005), fibrous crescents (p=0.0237), endocapillary hypercellularity (p=0.0449), and segmental scaring (p=0.0045) in LN group 1 compared to LN group 2 patients. Immunofluorescence did not show the significance for IgG, IgM, IgA, and C1q, and C3.
Conclusion: Our results suggest that B-cell intracellular IFNβ can be used in combination with other clinical diagnostic markers to identify patients at high risk of developing advanced LN. IFNβ blockade may be developed into individualized therapy for this subset of SLE patients.
To cite this abstract in AMA style:Alduraibi F, Fatima H, Chatham W, Hsu H, Mountz J. B Cell Intracellular IFNβ as a Unique Cellular Marker for the Development of Lupus Nephritis [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/b-cell-intracellular-ifn%ce%b2-as-a-unique-cellular-marker-for-the-development-of-lupus-nephritis/. Accessed December 5, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cell-intracellular-ifn%ce%b2-as-a-unique-cellular-marker-for-the-development-of-lupus-nephritis/