Adult-onset asthma and periocular xanthogranuloma associated with IgG4-related disease with infiltration of regulatory T cells

2016 ◽  
Vol 31 (2) ◽  
pp. e124-e125 ◽  
Author(s):  
Y. Honda ◽  
S. Nakamizo ◽  
T. Dainichi ◽  
R. Sasai ◽  
T. Mimori ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Adult Onset ◽  
Related Disease ◽  
Igg4 Related Disease

scholarly journals AB1068 REGULATORY EFFECT OF SHORT-TERM LOW DOSE OF IL-2 RESTORES REGULATORY T CELLS IN IgG4-RELATED DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1823.2-1823
Author(s):  
Y. Wu ◽  
X. C. Zhao ◽  
J. Luo
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Low Dose ◽  
Immune Cell ◽  
Interleukin 2 ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
The Absolute

Background:Little known about the roles of peripheral immune cell subsets in IgG4-related disease (IgG4-RD).Objectives:The aim of our study was to analyze the role of low-dose interleukin-2 (ld-IL2) on these cells in IgG4-RD.Methods:The percentage and absolute counts of lymphocyte subpopulations [CD3+ (T cells), CD4+, CD8+, CD19+ (B cells) and CD16+CD56+ (NK cells)] and CD4+T cell subsets (Th1, Th2, Th17, regulatory T (Treg)) using single platform flow cytometry in 25 IgG4-RD patients which were admitted and treated, as well as 24 healthy controls (HCs). Among IgG4-RD patients, 19 patients given only conventional treatments while 5 patients were were not only given conventional treatments but also received ld-IL2 (0.5 million IU/day) for 5 days.Results:We found that the absolute counts of T, CD4+T and Th1 cells were increased in the peripheral immune cells of IgG4-RD patients when compared with HCs. Meanwhile, the percentage of B, Th2, Th17 and Treg cells demonstrated significantly decreased. The ratio of Th1/Th2 and Th1/Treg in IgG4-RD patients were higher than that in HCs. After IL-2 administration, the absolute numbers of Treg cells increased dramatically, furthermore, the proportion of Treg cells had a trend towards higher values compared with those before treatment. Conversely, the ratio of Th2/Treg was downward. There were no any significant differences in the above subsets between before and after conventional treatments.Conclusion:Our findings support that the reduction of Treg cells in IgG4-RD patients, as well as ld-IL2 combined with conventional treatments were able to restore the Treg cells.References:[1]Akiyama M, Sasaki T, Kaneko Y, et al. Serum soluble interleukin-2 receptor is a useful biomarker for disease activity but not for differential diagnosis in IgG4-related disease and primary Sjögren’s syndrome adults from a defined population. Clin Exp Rheumatol, 2018.[2]Zhang SX, Wang J, Sun HH et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis, 2019.Disclosure of Interests:None declared

THU0007 Enhanced IGG4 Production by Follicular Helper Type 2 T Cells in IGG4-Related Disease

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 180.1-180
Author(s):  
M. Akiyama ◽  
H. Yasuoka ◽  
K. Yamaoka ◽  
K. Suzuki ◽  
Y. Kaneko ◽  
...  
Keyword(s):  
T Cells ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Follicular Helper ◽  
Helper Type

scholarly journals High-throughput sequencing of CD4+ T cell repertoire reveals disease-specific signatures in IgG4-related disease

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Liwen Wang ◽  
Panpan Zhang ◽  
Jieqiong Li ◽  
Hui Lu ◽  
Linyi Peng ◽  
...  
Keyword(s):  
T Cells ◽  
Length Distribution ◽  
Clonal Expansion ◽  
Healthy Controls ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Cdr3 Length ◽  
Relative Similarity

Abstract Background CD4+ T cells play critical roles in the pathogenesis of IgG4-related disease (IgG4-RD). The aim of this study was to investigate the TCR repertoire of peripheral blood CD4+ T cells in IgG4-RD. Methods The peripheral blood was collected from six healthy controls and eight IgG4-RD patients. TCR β-chain libraries of CD4+ T cells were constructed by 5′-rapid amplification of cDNA ends (5′-RACE) and sequenced by Illumina Miseq platform. The relative similarity of TCR repertoires between samples was evaluated according to the total frequencies of shared clonotypes (metric F), correlation of frequencies of shared clonotypes (metric R), and total number of shared clonotypes (metric D). Results The clonal expansion and diversity of CD4+ T cell repertoire were comparable between healthy controls and IgG4-RD patients, while the proportion of expanded and coding degenerated clones, as an indicator of antigen-driven clonal expansion, was significantly higher in IgG4-RD patients. There was no significant difference in TRBV and TRBJ gene usage between healthy controls and IgG4-RD patients. The complementarity determining region 3 (CDR3) length distribution was skewed towards longer fragments in IgG4-RD. Visualization of relative similarity of TCR repertoires by multi-dimensional scaling analysis showed that TCR repertoires of IgG4-RD patients were separated from that of healthy controls in F and D metrics. We identified 11 IgG4-RD-specific CDR3 amino acid sequences that were expanded in at least 2 IgG4-RD patients, while not detected in healthy controls. According to TCR clonotype networks constructed by connecting all the CDR3 sequences with a Levenshtein distance of 1, 3 IgG4-RD-specific clusters were identified. We annotated the TCR sequences with known antigen specificity according to McPAS-TCR database and found that the frequencies of TCR sequences associated with each disease or immune function were comparable between healthy controls and IgG4-RD patients. Conclusion According to our study of CD4+ T cells from eight IgG4-RD patients, TCR repertoires of IgG4-RD patients were different from that of healthy controls in the proportion of expanded and coding degenerated clones and CDR3 length distribution. In addition, IgG4-RD-specific TCR sequences and clusters were identified in our study.

Synergistic effect of IgG4 antibody and CTLs causes tissue inflammation in IgG4-related disease

2019 ◽  
Vol 32 (3) ◽  
pp. 163-174
Author(s):  
Takanori Sasaki ◽  
Taiki Yajima ◽  
Tatsuro Shimaoka ◽  
Shuhei Ogawa ◽  
Takashi Saito ◽  
...  
Keyword(s):  
T Cells ◽  
Synergistic Effect ◽  
Plasma Cells ◽  
Synergistic Effects ◽  
Lymphoid Tissues ◽  
Irreversible Damage ◽  
Tissue Specific ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Igg4 Antibody

Abstract IgG4-related disease (IgG4-RD) is characterized by multi-organ irreversible damage resulting from tissue-specific infiltration of IgG4+ plasma cells and cytotoxic T lymphocytes (CTLs). However, whether IgG4 antibody contributes to the inflammation remains unclear. In this study, we established a mouse model that enabled us to evaluate the pathogenic function of IgG4 antibodies in response to a tissue-specific autoantigen using recombinant ovalbumin (OVA)-specific human IgG4 monoclonal antibody (rOVA-hIgG4 mAb) and the mice expressing OVA of the pancreatic islets (RIP-mOVA mice). We found no inflammatory effect of rOVA-hIgG4 mAb transfer alone; however, co-transfer with OVA-specific CD8 CTLs (OT-I T cells) induced tissue damage with dense lymphocytic inflammation in the pancreas of RIP-mOVA mice. rOVA-hIgG4 mAb caused accumulation of conventional DC1 cells (cDC1s) in the lymphoid tissues, and the dendritic cells (DCs) activated the OT-I T cells via cross-presentation. We also revealed that the synergistic effects of CTLs and antibodies were observed in the other subclasses including endogenous antibodies if they recognized the same antigen. The transfer of OVA-specific CD4 helper T cells (OT-II T cells) into RIP-mOVA mice induced the production of anti-OVA antibody, which had a synergistic effect, through acquisition of a T follicular helper (TFH) phenotype. Moreover, using OT-II T cells deficient in Bcl6 caused lower anti-OVA antibody production and inflammation with OT-I T cells. Our results indicated that autoreactive IgG4 antibodies play an important role of the tissue-specific CTL response in IgG4-RD.

scholarly journals IgG4‐related disease: Association with a rare gene variant expressed in cytotoxic T cells

2019 ◽  
Vol 7 (6) ◽  
Author(s):  
John H. Newman ◽  
Aaron Shaver ◽  
Jonathan H. Sheehan ◽  
Simon Mallal ◽  
John H. Stone ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Cells ◽  
Disease Association ◽  
Gene Variant ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Rare Gene

scholarly journals Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease

Medicine ◽  
2015 ◽  
Vol 94 (43) ◽  
pp. e1916 ◽  
Author(s):  
Jonathan London ◽  
Antoine Martin ◽  
Michael Soussan ◽  
Isabelle Badelon ◽  
Thomas Gille ◽  
...  
Keyword(s):  
Rare Entity ◽  
Adult Onset ◽  
Strong Link ◽  
Related Disease ◽  
Igg4 Related Disease

scholarly journals Intrathecal activation of CD8 + memory T cells in IgG4‐related disease of the brain parenchyma

2021 ◽  
Author(s):  
Mirco Friedrich ◽  
Niklas Kehl ◽  
Niko Engelke ◽  
Josephine Kraus ◽  
Katharina Lindner ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Brain Parenchyma ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Cd8 Memory T Cells ◽  
The Brain
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