Expansion of circulating extrafollicular helper T-like cells in patients with chronic graft-versus-host disease

Jin, Hua; Yang, Kaibo; Zhang, Haiyan; Chen, Yanqiu; Qi, Hanzhou; Zhang, Fan; Huang, Fen; Xuan, Li; Lin, Ren; Zhao, Ke; Liu, Qifa

doi:10.1016/j.jaut.2019.03.006

Cited by 7 publications

(10 citation statements)

References 35 publications

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“…It has also been reported that the levels of IgG, especially IgG1, increased in Ro52-null mice with dermatitis (68). Our previous study showed that the levels of IgG1 correlated significantly with clinical cGVHD severity (11). We further examined the correlation between anti-Ro52 and IgG1 levels.…”

Section: Discussionmentioning

confidence: 84%

“…The diagnosis and grade of cGVHD on the day of sample collection, not at first diagnosis, were documented by clinical examination and laboratory testing [according to the National Institutes of Health (NIH) criteria] ( 30 ). Patients with active cGVHD were defined as requiring the addition of high-dose prednisone (≥2 mg/kg per day) or continued multiagent immunosuppression after sample collection ( 11 , 31 ). Patients without cGVHD were defined as patients who had not developed cGVHD by the time of sample collection.…”

Section: Methodsmentioning

confidence: 99%

“…(30). Patients with active cGVHD were defined as requiring the addition of highdose prednisone (≥2 mg/kg per day) or continued multiagent immunosuppression after sample collection (11,31). Patients without cGVHD were defined as patients who had not developed cGVHD by the time of sample collection.…”

Section: Gvhd Assessmentmentioning

confidence: 99%

“…Patients without cGVHD were defined as patients who had not developed cGVHD by the time of sample collection. Patients with previous cGVHD that had resolved or who became asymptomatic by the time of sample collection were not included (11,31).…”

Section: Gvhd Assessmentmentioning

confidence: 99%

“…The clinical symptoms of cGVHD are highly variable, including skin sclerosis, bronchiolitis obliterans, salivary, and lacrimal gland pathology (6,7). Chronic GVHD is an autoimmune-like syndrome caused by the interactions of donor CD4 + T and B cells and production of IgG (7)(8)(9)(10)(11). Recently, antibodies have been reported to play an important role in the development of cGVHD (12)(13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

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Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Yang

Chen

et al. 2020

Front. Immunol.

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Chronic graft-vs.-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that autoantibodies play an important role in the development of cGVHD. Anti-nuclear autoantibodies (ANA) is the most frequently detected autoantibodies in patients with cGVHD, but the role of anti-Ro52 autoantibodies (anti-Ro52) in cGVHD remains largely unknown. In this study, we analyzed autoantibodies from 84 patients after allo-HSCT, including 42 with active cGVHD and 42 without cGVHD. Autoantibodies were found in 36 (42.9%) patients. Among these autoantibody-positive patients, 28 (77.8%) patients had active cGVHD. The most frequent autoantibodies in patients with active cGVHD were ANA (50.0%), anti-Ro52 (28.6%) and anti-mitochondrial autoantibodies type 2 (4.8%). We further explored the association between anti-Ro52 and cGVHD. Patients with active cGVHD had higher anti-Ro52 levels than patients without cGVHD (P < 0.05). The increases of anti-Ro52 levels were more significant in patients with moderate/severe cGVHD compared to those of patients without cGVHD (P < 0.05). Stratified and multivariable logistic regression analysis demonstrated that moderate/severe cGVHD was an independent risk factor for the levels of anti-Ro52 (P < 0.01). ROC analysis confirmed anti-Ro52 as a risk factor for progression of skin cGVHD. Moreover, the anti-Ro52 levels were highly correlated with the levels of B cell-activating factor (BAFF) and IgG1 antibodies. Our study demonstrates that anti-Ro52 is associated with cGVHD. The increased levels of anti-Ro52 were associated with higher levels of BAFF and IgG1 antibodies, suggesting a mechanistic link between elevated anti-Ro52 levels and aberrant B cell homeostasis.

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Section: Discussionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Gvhd Assessmentmentioning

confidence: 99%

Section: Gvhd Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Yang

Chen

et al. 2020

Front. Immunol.

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Spatial and functional heterogeneity of follicular helper T cells in autoimmunity

Seth

Craft

2019

Current Opinion in Immunology

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Wnt/β-catenin signaling mediates the abnormal osteogenic and adipogenic capabilities of bone marrow mesenchymal stem cells from chronic graft-versus-host disease patients

Suo

et al. 2021

Cell Death Dis

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Chronic graft-versus-host disease (cGVHD) is the main cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mesenchymal stem cells (MSCs) in bone marrow (BM) remain unclear in the pathophysiology of cGVHD. In this study, we analyzed BM-MSCs from 66 patients after allo-HSCT, including 33 with active cGVHD and 33 without cGVHD. BM-MSCs showed similar morphology, frequency, phenotype, and proliferation in patients with or without cGVHD. MSCs from the active cGVHD group showed a decreased apoptosis rate (P < 0.01). Osteogenic capacity was increased while adipogenic capacity was decreased in the active cGVHD MSCs compared with no-cGVHD MSCs. The expressions of osteogenic gene RUNX2 and COL1A1 were higher (P < 0.001) while adipogenic gene PPAR-γ and FABP4 were lower (P < 0.001) in the active cGVHD MSCs than no-cGVHD MSCs. These changes were associated with the severity of cGVHD (P < 0.0001; r = 0.534, r = 0.476, r = −0.796, and r = −0.747, respectively in RUNX2, COL1A1, PPAR-γ, and FABP4). The expression of Wnt/β-catenin pathway ligand Wnt3a was increased in cGVHD-MSCs. The dysfunction of cGVHD-MSCs could be reversed by Dickkopf related protein 1(DKK1) to inhibit the binding of Wnt3a. In summary, the differentiation of BM-MSCs was abnormal in active cGVHD, and its underlying mechanism is the upregulated of Wnt3a through Wnt/β-catenin signaling pathway of MSCs.

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Expansion of circulating extrafollicular helper T-like cells in patients with chronic graft-versus-host disease

Cited by 7 publications

References 35 publications

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Spatial and functional heterogeneity of follicular helper T cells in autoimmunity

Wnt/β-catenin signaling mediates the abnormal osteogenic and adipogenic capabilities of bone marrow mesenchymal stem cells from chronic graft-versus-host disease patients

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