Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overproduction of autoantibodies by B cells and breaking self-tolerance of T cells and dendritic cells (DCs). However, little is known about the relationship between these immune cells in the etiology of SLE. Here, we found a novel DC subset and investigated the interaction among immune cell subsets in SLE.
Methods
Peripheral blood mononuclear cells were obtained from 44 patients with SLE, 20 with rheumatoid arthritis (RA), and 8 healthy donors (HD). Circulating B cells, T cells and DCs were defined based on comprehensive flow cytometric analysis for human immune system termed ‘the Human Immunology Project’ by NIH/FOCIS.
Results
The proportion of central memory B cells, effector B cells, and plasmablasts was higher (p=0.04, p=0.001, respectively), whereas the proportion of IgM memory B cells was lower (p<0.001) in SLE, compared to HD and RA. For T cell subsets, the proportion of effector memory T cells was highest in SLE (p=0.04). For DCs which were defined as CD3–CD14–CD19–CD20–HLA-DRhi, the percentage of CD11c+ myeloid DCs significantly decreased in SLE (p<0.001), while that of CD123+ plasmacytoid DCs was comparable among SLE, HD and RA (p=0.48). Interestingly, DCs that expressed neither CD11c nor CD123 were detected exclusively in SLE but not in the control or RA (p<0.001). To assess pathological relevance of this double-negative DC subset in SLE, we calculated the Pearson product-moment correlation coefficient among immune cell subsets and also conducted correlation clustering analysis. Among them, Double-negative DCs characteristically clustered with the central memory B cells and plasmablasts, and was correlated positively with plasmablasts (p=0.04) and negatively with myeloid DCs (p<0.001) and plasmacytoid DCs (p=0.04). Furthermore, the percentage of double-negative DCs was correlated with scores of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index in patients. In 13 patients with treatment-naive in this cohort, the percentage of double-negative DCs was correlated positively with scores of SLEDAI and BILAG index as well as serum anti-dsDNA antibody levels and negatively with CH50 levels.
Conclusion
These results suggest that a novel CD123–CD11c– DC subset characteristically increased in relation to central memory B cells and plasmablasts in patients with treatment-naïve SLE. Furthermore, the frequencies of novel DC subsets were correlated with scores of SLEDAI and BILAG and serum levels of anti-dsDNA antibody, indicating that this DC subset may contribute to disease activity and autoantibody production. Although further studies are required, our findings would shed light on the activation mechanism of autoantibody production through the interaction between a novel DC subset and central memory B cells/plasmablasts in SLE and could be potentially useful in the design of new therapeutic strategies.
Disclosure:
S. Kubo,
None;
S. Nakayamada,
None;
N. Yunoue,
None;
M. Yoshikawa,
None;
K. Yamaoka,
None;
Y. Tanaka,
BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbvie and Daiichi-Sankyo,
2,
UCB, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD and Asahi Kasei,
5,
UCB, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD and Asahi Kasei,
8.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-cd123cd11c-dendritic-cell-subset-increased-in-relation-to-disease-activity-in-patients-with-systemic-lupus-erythematosus/