Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Allogeneic Mesenchymal Stem Cells Inhibited OAZ Expression in Patients with Systemic Lupus Erythematosus.
Feng1, Xuebing, Li2, Rongliang, Huang2, Jing, Wang2, Dandan, Ma2, Xiaolei, Tsao3, Betty P., Sun2, Lingyun
Allogeneic mesenchymal stem cell transplantation (MSCT) has been applied to successfully treat patients with refractory systemic lupus erythematosus (SLE) (Sun et al A & R, 2010). However, the underlying mechanism is still unclear. Recently we have shown Olf1/EBF associated zinc finger protein (OAZ), a novel lupus susceptibility gene, involves in the production of antinuclear antibody (ANA) that is partly through the regulation of ID genes. This study is to explore whether allogeneic MSCT helps down-regulate elevated OAZ expression in SLE patients.
Study protocol was approved by the hospital's Ethics Committee. MSCs were isolated and expanded from bone marrow of 5 SLE patients and 6 healthy subjects. After culturing for 3 passages, MSCs were harvested and mRNA levels of OAZ and ID1, ID3, two downstream genes of OAZ, were measured by qRT-PCR. MSCs expanded from umbilical cord (9 cases) or bone marrow cells (1 case) of healthy donors were infused once to 10 refractory SLE patients at 106cells/kg of body weight. Peripheral blood cells (PBLs) were collected before and one week as well as four weeks after MSCT, and transcript levels of OAZ and IDs were measured. Concurrently, serum levels of IL-10, IL-12, IL-21, CCL2 and ANA were tested by ELISA. Relationships between gene expressions and cytokine levels as well as ANA values were analyzed. Data were shown as mean +/- SEM.
Compared to PBLs, MSC expression of OAZ transcripts was 150 and 110 times higher in SLE patients and normal controls, respectively. OAZ expressions of MSCs in SLE patients were elevated compared to those in normal subjects (p = 0.03), but expressions of ID1 and ID3 were not different. Ten SLE patients (9 female and 1 male, 32.2 ± 3.7 years old) who accepted MSCT had decreased OAZ expressions in PBLs by 42.6%±17.1% one week after MSCT compared to those before MSCT (p < 0.05) with concomitant reduction in disease activity (SLEDAI score was 14.9 ± 0.6 before MSCT, 13.0 ± 0.5 one week later) which continued to drop further four weeks after the transplant (a reduction of 37.6%±12.4% compared to those at one week, p < 0.05). Peripheral gene expressions of ID1 and ID3 were also significantly down-regulated after MSCT (p < 0.05). Four weeks after MSCT, serum levels of IL-10, IL-21 and ANA were significantly decreased (p < 0.05 in all), while CCL2 level was elevated (p <0.05) compared to the baseline levels. Compared to the value before MSCT, inhibited peripheral OAZ expression four weeks after MSCT was inversely correlated with reduced IL-21 levels (r =-0.88, p < 0.05) and ANA values (r =-0.91, p < 0.01) but positively correlated with increased CCL2 levels (r = 0.92, p < 0.01).
OAZ is highly expressed in MSCs from SLE patients. Allogeneic MSCT helps down-regulate OAZ expression and its downstream components, which may account for the ameliorated SLE disease activity. The differential expressions of ID1 and ID3 in peripheral blood cells but not MSCs support that MSCs could exert their roles through the regulation of other cells types.
To cite this abstract, please use the following information:
Feng, Xuebing, Li, Rongliang, Huang, Jing, Wang, Dandan, Ma, Xiaolei, Tsao, Betty P., et al; Allogeneic Mesenchymal Stem Cells Inhibited OAZ Expression in Patients with Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1182