Predominant Infiltration of Monocytes in Chronic Graft-Versus-Host Disease

Namba, Noriko; Shinagawa, Katsuji; Fujii, Nobutaka; Maeda, Yoshinobu; Ishimaru, Fumihiko; Ikeda, Kazuma; Matsui, Toshimitsu; Tanimoto, Mitsune; Katayama, Yoshio

doi:10.1097/01.tp.0000245080.71722.87

Cited by 15 publications

(20 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…39 Predominant infiltration of monocytes, recruited from the circulation to target organs, was present in the epidermis, as well as in the conjunctiva, in patients with chronic GVHD. 40,41 However, these reports did not show how monocytes contribute to the pathogenm. Hirayama et al 46 haematologica | 2013; 98(1) The correlation of the number of IL-10 SFC with plasma laminin, procollagen type I, or fibronectin levels was analyzed in patients with active cGVHD.…”

Section: Discussionmentioning

confidence: 87%

Interleukin-10 spot-forming cells as a novel biomarker of chronic graft-versus-host disease

et al. 2012

View full text Add to dashboard Cite

ABSTRACTcytokine SFC in patients following HSCT and correlated the results with clinical findings. Furthermore, expression of CD29 (b1 integrin) on monocytes was correlated with plasma levels of fibronectin in patients with active chronic GVHD. Design and Methods PatientsFifty-seven patients who underwent allogeneic HSCT between 1995 and 2009 were included in this study. The patients' demographic data are shown in Table 1. Sixteen patients with chronic GVHD were grouped into mild (n=7), moderate (n=8), and severe (n=1) categories based on the NIH chronic GVHD consensus criteria. 5 According to Sarantopoulos's definition of chronic GVHD activity, patients were subclassified into those with no, active, and inactive chronic GVHD. 28 Patients who never developed chronic GVHD (n=41) were designated as "no chronic GVHD". Patients with active chronic GVHD (n=14) were more likely to be receiving immunosuppressive therapy. Inactive chronic GVHD (n=10) was determined by clinical assessment and included patients who had achieved a complete response to immunosuppressive therapy at the time of analysis. The number of patients with active and inactive chronic GVHD overlapped during the clinical course. Disease activity was assessed without knowledge of the laboratory results. The median time of the analysis was 48 (range, 4-204), 52 (5-142), and 55 (4-151) months after transplantation for patients with no, active, and inactive chronic GVHD, respectively.This study was conducted according to the principles expressed in the Declaration of Helsinki and approved by the Institutional Ethics Committee Review Board at Mie University Hospital. The study was registered with the national regulatory authority (UMIN-Clinical Trials Registry). All participants or their guardians provided written informed consent for the collection of samples and subsequent analyses. Diagnosis of chronic graft-versus-host disease and processing of samplesThe diagnosis of chronic GVHD requires the presence of at least one diagnostic manifestation of the disease or at least one distinctive manifestation, with the diagnosis confirmed by pertinent biopsy, laboratory tests, or radiology in the same or another organ.5,29 Diagnostic manifestations of chronic GVHD were found in the skin, nails, mouth, eyes, lungs, gastrointestinal tract, and liver. The grade of chronic GVHD was determined according to NIH consensus criteria. 5,30 Peripheral blood mononuclear cells (PBMC) were obtained from patients with no evidence of infection, and the diagnoses were confirmed by laboratory testing or radiology, at least 100 days after allogeneic HSCT. The total numbers of white blood cells, lymphocytes, and monocytes were analyzed by an automatic blood cell counter (Sysmex K4500, Toa Medical Electronics, Tokyo, Japan). Flow cytometry and cell separationCells were stained with fluorescein-conjugated monoclonal antibodies to human anti-CD3, CD4, CD8, CD11c, CD16, CD19, CD25, CD29, CD33, CD56, CD123 (BD Biosciences, San Jose, CA, USA), CD14 (Beckman Coulter, CA, USA), CD68, interle...

show abstract

Section: Discussionmentioning

confidence: 87%

Interleukin-10 spot-forming cells as a novel biomarker of chronic graft-versus-host disease

et al. 2012

View full text Add to dashboard Cite

show abstract

“…These processes may have debilitating consequences on patient quality of life because of substantive organ damage requiring prolonged immunosuppression. [9][10][11][12][13][14][15][16][17][18][19][20] Previous studies have shown abnormalities in the oral and intestinal mucosa, characterized by thickening of the mucosa and the lichenoid aspect, in addition to decreased lymphocytic regulators (CD4 ϩ ) and increased cytotoxic lymphocytes (CD8 ϩ ). [12][13][14][15][16][17][18][19][20] Although the diagnosis of GVHD has been standardized, the precise pathophysiology of the disease remains unknown and, furthermore, abnormalities in the nasal mucosa are poorly described.…”

mentioning

confidence: 99%

Histological Features of the Nasal Mucosa in Hematopoietic Stem Cell Transplantation

Ortiz

Sakano

Meirelles

et al. 2011

Am J Rhinol�Allergy

View full text Add to dashboard Cite

show abstract

“…These relatively undifferentiated monocytes do not represent the complex populations of myeloid-derived cells in CGVHD affected tissue. Plasmacytoid and myeloid dendritic cells, and specialized scavenger and CX3CR1+ inflammatory macrophages are key elements of CGVHD infiltrates in tissues (4, 13). The precursors of these cells are often depleted in the circulation of CGVHD patients (see dendritic cells in Supplemental Figure S4 A,B) (13).…”

Section: Discussionmentioning

confidence: 99%

“…Plasmacytoid and myeloid dendritic cells, and specialized scavenger and CX3CR1+ inflammatory macrophages are key elements of CGVHD infiltrates in tissues (4, 13). The precursors of these cells are often depleted in the circulation of CGVHD patients (see dendritic cells in Supplemental Figure S4 A,B) (13). Alterations in gene patterns that occur during terminal differentiation of myeloid infiltrates in tissues may not be present in circulating monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Monocytes circulate throughout CGVHD patients, being exposed to the operant cytokine conditions in multiple locations. Monocyte-derived lineages are highly relevant to CGVHD, because the circulating monocytes emigrate into tissues, differentiating into scavenger macrophages, antigen presenting cells and regulators of fibrosis in CGVHD (4, 13). Since these recruited monocytes are constantly replenished from the marrow, their transcriptome provides a snapshot of prevailing cytokine conditions over a narrow window of time, yet this information can be tracked serially through multiple time points in CGVHD development.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease

Hakim

Memon

Jin

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Although Chronic Graft-versus-Host Disease (CGVHD) is the primary non-relapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: (1) Interferon-inducible genes and (2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation and antigen presentation) were concurrently upregulated in CGVHD monocytes compared to normal and nonCGVHD controls. IFN-inducible chemokines were elevated in both lichenoid and sclerotic CGHVD plasma and linked to CXCR3+ lymphocyte trafficking. Furthermore, the IFN-inducible genes CXCL10 and TNFSF13B (BAFF) levels were correlated at both the gene and plasma levels, implicating IFN-induction as a factor in elevated BAFF levels in CGVHD. In the second pathway, DAMP/PAMP receptor genes capable of inducing Type I IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to CGVHD activity in skin, mucosa and glands, and expression of TLR and RIG-1 receptor genes correlated with upregulation of Type I IFN-inducible genes in monocytes. Finally, in serial analyses following transplant, IFN-inducible and damage-response genes were upregulated in monocytes at CGVHD onset and declined upon therapy and resolution in both lichenoid and sclerotic CGVHD patients. This interlocking analysis of IFN-inducible genes, plasma analytes and tissue immunohistochemistry strongly supports a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD.

show abstract

Predominant Infiltration of Monocytes in Chronic Graft-Versus-Host Disease

Cited by 15 publications

References 17 publications

Interleukin-10 spot-forming cells as a novel biomarker of chronic graft-versus-host disease

Interleukin-10 spot-forming cells as a novel biomarker of chronic graft-versus-host disease

Histological Features of the Nasal Mucosa in Hematopoietic Stem Cell Transplantation

Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease

Contact Info

Product

Resources

About