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Abstract Number: 1238

Proportion of Peripheral Plasmacytoid Dendritic Cells and Plasmablasts Reflects Disease Activity in IgG4-related Disease

Mitsuhiro Akiyama1, Katsuya Suzuki1, Yoshiaki Kassai2, Takahiro Miyazaki2, Rimpei Morita3, Akihiko Yoshimura3 and Tsutomu Takeuchi1, 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2Inflammation Drug Discovery Unit, Takeda Pharmaceutical Company Limited, Kanagawa, Japan, 3Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: dendritic cells and flow cytometry, Disease Activity, IgG4 Related Disease, Plasmablasts

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Session Information

Title: Miscellaneous Rheumatic and Inflammatory Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disease with multi-organ system involvement. Affected patients frequently have a history of bronchial asthma and allergic rhinitis. The reported pathogenesis of IgG4-RD describes the clear involvement of excessive Th2 cells and regulatory immune reaction in addition to plasma cells 1). However, peripheral immune cell phenotype, which reflects disease status, has not been comprehensively evaluated. Our aim was to definitively determine peripheral blood cell abnormalities and their correlation with disease activity in patients with IgG4-RD.

Methods

Peripheral blood samples were obtained from active untreated IgG4-RD patients (n=11) and healthy controls (n=16). Comprehensive immunophenotyping assay with information on activation status was done by multi-color flow cytometry, and the proportion of peripheral blood mononuclear cells (PBMCs), including T cells (naïve/memory, Th1/2/17, Treg, and Tfh), B cells (naïve/memory, plasmablast, Breg), monocytes (classical, intermediate, non-classical) and dendritic cells (myeloid, plasmacytoid), and their activity status were precisely defined. Disease activity was measured using the IgG4-RD responder index (RI). Statistical analysis was done using the Mann-Whitney U test and Spearman rank correlation coefficient test.

Results

The proportion of plasmablasts (CD19+CD20-CD27+CD38+), memory Th2 cells (CD3+CD4+CXCR3-CCR6-CD45RA-), Tregs (CD3+CD4+CD25+CD127low), Tfh (CD3+CD4+CXCR5+), and mDCs (CD3-CD19-CD14-HLA-DR+CD1c+CD303-) in peripheral blood was significantly increased in IgG4-RD patients compared with HC, whereas the proportion of pDCs (CD3-CD19-CD14-HLA-DR+CD1c-CD303+)was significantly decreased. Interestingly, the proportion of pDCs in total DCs was negatively correlated with IgG4-RD RI (r=-0.778, p=0.005) while the proportion of plasmablasts in CD19+cells was positively correlated with RI (r=0.701, p=0.016). Further, the increased proportion of plasmablasts was positively correlated with serum IgG4 level (r=0.718, p=0.013) while the decreased proportion of pDCs tended to be negatively correlated with the number of affected organs (r=-0.518, p=0.061). 

Conclusion

Our comprehensive analysis identified distinct proportional changes in PBMCs in IgG4-RD. In particular, the decrease in pDCs and increase in plasmablasts were strongly linked with disease activity. These combined measurements are expected to be clinically useful surrogate cell markers. This newly identified decrease in circulating pDCs may be involved in the pathogenesis in IgG4-RD via the recently described role in the enhancement of Th2 response 2).

References: 1) Stone JH et.al. N Engl J Med 2012;366:539-51

            2) Maazi H et.al. Allergy 2013;68:695-701


Disclosure:

M. Akiyama,
None;

K. Suzuki,
None;

Y. Kassai,

Employee of Takeda Pharmaceutical Company Limited,

3;

T. Miyazaki,

Employee of Takeda Pharmaceutical Company Limited,

3;

R. Morita,
None;

A. Yoshimura,
None;

T. Takeuchi,

Grant/research support: Abbott Japan Co., Ltd., Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Sanofi–Aventis K,

2.

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