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Surface APRIL Is Elevated on Myeloid Cells and Is Associated with Disease Activity in Patients with Rheumatoid
Abby Jones Weldon1, Ioana Moldovan2, Marven G Cabling2
1From the Center for Health Disparities and Molecular Medicine, Department of Microbiology and Molecular Genetics, Department of Medicine, Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Department of Pathology and Human Anatomy, Loma Linda University, Loma Linda; Division of Rheumatology, Beaver Medical Group, Redlands, California, USA.A.J. Weldon, MS; A. Benitez, PhD, Center for Health Disparities and Molecular Medicine, and Department of Microbiology and Molecular Genetics, Loma Linda University; I. Moldovan, MD, Department of Medicine, Loma Linda University, and Division of Rheumatology, Beaver Medical Group; M.G. Cabling, MD; S. Hsu, MD; N. Daoud, MD; K. Colburn, MD, Department of Medicine, Loma Linda University; E.A. Hernandez, PhD, Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Loma Linda University; J. Gonzalez, BS; A. Parra, BS, Center for Health Disparities and Molecular Medicine, Loma Linda University; K.J. Payne, PhD, Center for Health Disparities and Molecular Medicine, and Department of Pathology and Human Anatomy, Loma Linda University. aweldon@llu.edu.
Objective:
To assess surface APRIL (a proliferation-inducing ligand; CD256) expression by circulating myeloid cells in rheumatoid arthritis (RA) and to determine its relationship to disease activity.
Methods:
Peripheral blood mononuclear cells (PBMC) and plasma were obtained from patients with RA and healthy donors. PBMC were stained for flow cytometry to detect surface APRIL and blood cell markers to identify circulating myeloid cell subsets. Based on CD14 and CD16 phenotypes, monocyte subsets described as classical (CD14+CD16-), intermediate (CD14+CD16+), and nonclassical (CD14loCD16+) were identified. Levels of surface APRIL expression were measured by flow cytometry and median fluorescence intensity was used for comparisons. Levels of soluble APRIL in the plasma were determined by ELISA. Disease activity was measured by the Disease Activity Score in 28 joints.
Results:
In patients with RA, total myeloid cells showed expression of surface APRIL that correlated with disease activity and with plasma APRIL levels observed in these patients. In healthy donors, classical monocytes were composed of > 80% of circulating monocytes. However, in patients with RA, the intermediate and nonclassical subsets were elevated and made up the majority of circulating monocytes. In contrast to healthy donors, where high levels of surface APRIL were only observed in nonclassical monocytes, patients with RA showed high levels of surface APRIL expression by all circulating monocyte subsets.
Conclusion:
Surface APRIL is elevated in circulating myeloid cells in patients with RA where it is highly correlated with disease activity. Patients with RA also showed skewing of monocytes toward subsets associated with secretion of tumor necrosis factor-α and/or interleukin 1β.
Insights
Surface APRIL, a proliferation-inducing ligand, is elevated in myeloid cells of rheumatoid arthritis (RA) patients and correlates with disease activity. RA patients also exhibit altered monocyte subsets linked to inflammation.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
- Myeloid cells play a crucial role in the inflammatory processes of RA.
- APRIL (a proliferation-inducing ligand; CD256) is a cytokine involved in immune regulation.
Purpose of the Study:
- To investigate surface APRIL expression on circulating myeloid cells in RA patients.
- To determine the correlation between surface APRIL expression and disease activity in RA.
- To analyze the distribution of monocyte subsets in RA patients.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) and plasma were collected from RA patients and healthy donors.
- Flow cytometry was used to detect surface APRIL and identify monocyte subsets (classical, intermediate, nonclassical) based on CD14 and CD16 expression.
- ELISA measured soluble APRIL levels in plasma, and Disease Activity Score in 28 joints (DAS28) assessed disease activity.
Main Results:
- Patients with RA exhibited elevated surface APRIL expression on total myeloid cells, which correlated with disease activity and plasma APRIL levels.
- RA patients showed a shift in monocyte populations, with increased intermediate and nonclassical subsets compared to healthy donors.
- High surface APRIL expression was found on all monocyte subsets in RA patients, unlike healthy donors where it was primarily on nonclassical monocytes.
Conclusions:
- Surface APRIL is upregulated on circulating myeloid cells in RA and is strongly associated with disease activity.
- RA patients display altered monocyte subset distribution, favoring those implicated in pro-inflammatory cytokine production (TNF-α, IL-1β).
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