Blood Res.  2013 Mar;48(1):16-23. 10.5045/br.2013.48.1.16.

Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

• Lee TH
• Lee JY
• Park S
• Shin SH
• Yahng SA
• Yoon JH
• Lee SE
• Cho BS
• Kim YJ
• Lee S
• Min CK
• Kim DW
• Lee JW
• Min WS
• Park CW
• Kim HJ

• KMID: 2270721
• DOI: http://doi.org/10.5045/br.2013.48.1.16

Abstract

BACKGROUND
Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored.
METHODS
Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study.
RESULTS
Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients.
CONCLUSION
This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.

Keyword

Suppressor of cytokine signaling proteins; Graft vs. host disease; Quantitative real-time polymerase chain reaction; Allogeneic transplantation

MeSH Terms

Anemia, Aplastic
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
Interferon-gamma
Interleukins
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukocytes
Myelodysplastic Syndromes
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Reverse Transcription
Siblings
Suppressor of Cytokine Signaling Proteins
T-Lymphocytes
Tissue Donors
Transplantation, Homologous
Unrelated Donors
Interferon-gamma
Interleukins
Suppressor of Cytokine Signaling Proteins

Figure

• 

  Fig. 1 Comparison of SOCS genes in normal donors and GVHD recipients post HSCT. Mononuclear cells (MNCs) from recipients were isolated and subjected to qRT-PCR. (A, left) Data showed that the none-GVHD group (N=21) exhibited a significantly higher level of SOCS1 expression compared to the cGVHD group (N=17). (A, right) SOCS3 expression levels were low in the grade II-IV aGVHD (N=18), cGVHD, and none-GVHD groups compared to normal donors (N=55). (B) SOCS1 and SOCS3 expression levels in grade II aGVHD (N=14) differed significantly compared to those in normal donors. (C, left) SOCS1 expression differed significantly between the severe cGVHD (N=10) and the none-GVHD groups. (C, right) SOCS3 expression was lower in the mild-moderate cGVHD (N=7) group than in the none-GVHD and severe cGVHD groups. P values in (A-C) indicate significant differences relative to each comparison group.

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