Inflammation ( # 2015) DOI: 10.1007/s10753-015-0170-9
Decreased UBASH3A mRNA Expression Levels in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus Jie Liu,1,2 Jing Ni,1 Lian-Ju Li,1 Rui-Xue Leng,1 Hai-Feng Pan,1 and Dong-Qing Ye1,3
Abstract—Increasing evidence has demonstrated the association between UBASH3A gene and multiple autoimmune diseases (ADs). The aim of our study was to explore the potential effect of UBASH3A messenger RNA (mRNA) expression and its role in the pathogenesis of systemic lupus erythematosus (SLE). UBASH3A mRNA levels were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in total RNA, isolated from the peripheral blood mononuclear cells (PBMCs) of 32 SLE patients and 30 healthy donors with TRIzol Reagent. The expression level of UBASH3A mRNA was significantly reduced in PBMCs from SLE patients when compared with healthy controls (p = 0.002). UBASH3A mRNA expression levels in lower active SLE were significantly lower than that in inactive SLE groups (p =0.000). There was a negative association between mRNA levels of hyper-active and lower-active SLE patients (p = 0.000). Moreover, a significant negative correlation between UBASH3A mRNA expression and the onset age of SLE patients was found (p = 0.044). A negative correlation was found between UBASH3A mRNA expression and SLEDAI (p = 0.049). Nevertheless, no significant difference was found between patients with lupus nephritis (LN) and those without LN (p =0.392). The presence of leukopenia, positive for anti-dsDNA antibody and anti-SSB antibody were associated with UBASH3A mRNA levels in SLE patients (all p < 0.05). The dysregulation of UBASH3A mRNA levels in SLE patients and their correlations with experimental parameters suggested that UBASH3A may involve in the pathogenesis of SLE. KEY WORDS: UBASH3A; systemic lupus erythematosus; real-time reverse transcription-polymerase chain reaction; messenger RNA.
INTRODUCTION Systemic lupus erythematosus (SLE) is a complex, heterogenous autoimmune disease (AD) due to immunopathogenic abnormalities [1]. Immune dysregulation leads to excess production of autoantibodies and immune complex deposition, excess complement 1
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, People’s Republic of China 2 Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330029Jiangxi, People’s Republic of China 3 To whom correspondence should be addressed at Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, People’s Republic of China. E-mail: [email protected]
activation, and then immune damage to different organs and tissues [2]. The etiology of SLE is still incompletely understood. Genetic susceptibility and environmental factors have been reported to be involved in the initiation and promotion of this disease [3]. A combination of genome-wide association studies (GWAS) and casecontrol studies have identified more than 30 robust genetic susceptibility genes or loci in SLE [4–9]. However, the available risk variants explain only a small proportion of the predicted genetic heritability of SLE. Thus, the genetic basis of this disease remains to be elucidated. Proteins of the UBASH3/STS/TULA family recently recognized as potent regulators of cellular functions [10]. UBASH3A protein product contains interactive ubiquitinassociated (UBA) and Src-homology 3 (SH3) domains as well as a histidine phosphatase domain [11]. The
0360-3997/15/0000-0001/0 # 2015 Springer Science+Business Media New York
Liu, Ni, Li, Leng, Pan, and Ye UBASH3A gene is located on human chromosome 21q22.3, spans 40 kb and contains 15 exons [12]. UBASH3A is expressed predominantly in T cells suppressing T cell receptor signaling, underscoring antigen presentation to T cells as a key mechanism of disease pathogenesis [13]. Intriguingly, TULA-encoding (UBASH3A) alleles or phenotypes were found to be associated with some ADs [14–17]. For instance, UABSH3A was found to be associated with type 1 diabetes [18]. The discovery of UBASH3A as a novel susceptibility gene for human type 1 diabetes was confirmed by another study conducted in patients with Graves’ disease. Additionally, the UBASH3A rs3788013 polymorphism was shown to be associated with the presence of autoantibody to the thyroid peroxidase [17]. A statistically significant association between UBASH3A and generalized vitiligo was also observed [19]. Moreover, there was an association between UBASH3A and both rheumatoid arthritis and celiac disease for which epidemiological studies suggested the existence of a shared genetic background [20]. Collectively, these observations were in favor of an important role of UBASH3A in cellular regulation. Thus, the critical role of UBASH3A proteins in controlling T cell responses and, in regulation of T-cell-dependent findings in mouse experimental models showed that this protein may play a role in ADs [21, 22]. Although the association of UBASH3A gene polymorphisms with some autoimmune disease has been confirmed, messenger RNA (mRNA) expression levels of UBASH3A in patients with SLE remain unclear. In this study, we explored the mRNA expression levels of UBASH3A gene in PBMCs from patients with SLE and healthy controls. The association of SLE disease activity index (SLEDAI) scores and clinical data of SLE with the mRNA expression levels of UBASH3A were also analyzed.
MATERIALS AND METHODS Patient and Controls Thirty-two patients (30 women and 2 men, mean±SD age of 36.63±13.51 years, average SLEDAI 10.97±6.68) with SLE and 30 healthy controls (28 women and 2 men, mean±SD age of 32.03±9.61 years) with available RNA sample were performed by an analysis of mRNA for UBASH3A. The patients were recruited from the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital. All the patients were diagnosed in
accordance with the American College of Rheumatology (ACR) classification criteria revised in 1997 [23]. Sex- and age-matched controls were selected from healthy blood donors. Lupus nephritis (LN) was defined by the ACR criteria, i.e., according to any one of the following: persistent proteinuria (≥0.5 g/day) or the presence of active cellular casts, or biopsy evidence of LN [1]. Healthy controls were mainly recruited from the general population, healthy blood donors, and laboratory personnel. Healthy controls with no history of SLE, other inflammatory/ disease autoimmune, or cancer were recruited in our study. SLE disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 score [24]. The SLEDAI score was determined for each patient at the time of the blood draw. The SLEDAI was divided into three categories: patients were categorized as having hyper-active disease (scores >14), lower active disease (4 < SLEDAI score ≤ 14) or inactive disease (scores ≤4) based on the SLEDAI results [1]. The protocol for our study was consistent with the provisions of the World Medical Association Declaration of Helsinki. Peripheral bloods were obtained from the patients before they took any immunosuppressive drug, cytotoxic or glucocorticoid drugs. Real-Time Quantitative PCR PBMC blood samples obtained from SLE and healthy controls were prepared from EDTA-anticoagulated blood by Ficoll-Hypaque density gradient centrifugation. Total RNA was extracted from PBMCs by using TRIzol Reagent (Invitrogen life Technologies, Carlsbad, CA, USA) followed by RevertAid First Strand cDNA Synthesis Kit (Thermo Scientific, USA). RT-qPCR was performed to compare the mRNA expression of the UBASH3A gene (sense primer: 5′-GGACTTG-CACGACTAA-3′, antisense primer: 5′CCGTACGTCAATTGAC-3′). The assays were performed on ViiA™ 7 Real-Time PCR System (Applied Biosystems). Four microliters of cDNA (from a total 20μl reaction volume) was used in a 20-μl reaction. The RTqPCR reactions contained 10 μl TaqMan ® Gene Expression Master Mix, 1 μl Assay, and 5 μl H2O. Cycle conditions were as follows: pre-run for 2 min at 50 °C, incubation at 95 °C for 10 min, and 40 cycles of PCR at 95 °C for 15 s and at step 60 °C for 1 min. The RT-qPCR was run in duplicate, and the mRNA expression was determined by comparison with housekeeping gene β-actin from the same sample as internal control. Additionally, the relative expression levels were calculated using the 2−△△Ct method as described previously [25].
Decreased UBASH3A mRNA Levels in PBMCs from SLE Patients Collection of Clinical and Laboratory Data Clinical manifestations of SLE patients such as lupus nephritis, arthritis, skin rash, oral ulcers, and fever were recorded. Laboratory abnormalities , including thrombocytopenia (0.5 g/day), elevated erythrocyte sedimentation rate (ESR) (>20 mm/h), the presence of anti-Sm, anti-SSA, anti-SSB, anti-dsDNA, and serum levels of C3 and C4 were also retrieved from the medical record. Statistical Analysis Comparison of mRNA expression levels of UBASH3A between different groups were evaluated using the nonparametric Mann-Whitney U test. Quantitative variables were described using mean ± SD. Nonparametric distribution data were expressed as the median value and interquartile range (IQR). For the correlation analysis between UBASH3A mRNA levels and SLEDAI, Spearman’s rank correlation coefficient was used. A twosided p value of less than 0.05 was accepted as statistically significant. All calculations were analyzed by SPSS 11.5 software (SPSS Inc., USA).
RESULTS The demographic characteristics, clinical manifestations, and laboratory measurements of the SLE patients and healthy controls are shown in Table 1. The mean age of SLE patients was 36.63±13.51 years, and 93.75 % of them were women (Table 1). The mean age of healthy controls was 32.03±9.61 years, and 93.33 % of them were women. Clinical manifestations of SLE patients mainly included lupus nephritis (37.50 %), skin rash (34.38 %), fever (34.38 %), and arthritis (21.88 %). Experimental parameters of SLE patients were as follows in order of decreasing frequency: increased level of ESR (75.00 %), decreased level of C3 (68.75 %), the positive percentage of anti-SSA/ Ro (56.25 %), and anti-RNP (46.88 %). mRNA Expression of UBASH3A in PBMCs from SLE Patients and Healthy Controls The UBASH3A mRNA expression levels in PBMCs from 32 patients with SLE and 30 healthy subjects were analyzed by RT-qPCR. The data were normalized to housekeeping gene (β-actin). As shown in Table 2, the relative UBASH3A mRNA expression level was significantly
reduced in PBMCs from SLE patients when compared with healthy controls (p=0.002). In addition, UBASH3A mRNA levels in lower active SLE were significantly lower than that in inactive SLE groups (p=0.000). We also found a negative association between mRNA levels of hyperactive SLE and lower-active SLE patients (p = 0.000). Moreover, a significant negative correlation was found between UBASH3A mRNA expression and the age of onset in SLE patients (rs =−0.358, p=0.044) (Fig. 1). The mRNA expression was higher in patients with LN than that of those without LN, but no significant difference between the two groups was found (p=0.392). Association Between UBASH3A mRNA Expression Levels and SLEDAI or Clinical Data in SLE Patients We observed a negative correlation between UBASH3A mRNA expression and SLEDAI in SLE patients (rs =−0.350, p=0.049) (Fig. 2). We also analyzed the associations of UBASH3A mRNA levels with major laboratory and clinical parameters of SLE, and the results showed that the UBASH3A mRNA level were statistically significantly decreased in patients with leukopenia (p = 0.035) and anti-dsDNA antibody-positive group (p = 0.032). Additionally, the UBASH3A mRNA level was statistically significantly higher in the anti-SSB positive than that of anti-SSB antibody-negative group (p=0.016). However, no association of UBASH3A mRNA expression level with other clinical and laboratory parameters was found (Tables 3 and 4).
DISCUSSION SLE is a multiorgan autoimmune disease characterized by producing a large quantity of autoreactive antibodies, complements activation, and immune complex deposition, causing tissue and organ damage [26]. The pathogenesis of SLE is complex and includes genetic, environmental, and immunological factors. UBASH3A is characterized by a histidine as the essential residue in the active site, which could be added to the protein tyrosine phosphatase (PTP) superfamily [27]. UBASH3A expressed predominantly in T cells suppressing T cell receptor (TCR) signaling [21]. In addition, UBASH3A promote the dephosphorylation of the TCR signaling and function as a key negative regulator of TCR signaling [28]. Evidence of both B and T lymphocytes hyper-reactivity is typically found in AD [29]. Dysregulation of UBASH3A gene lowers the threshold of T cell activation and leads to
Liu, Ni, Li, Leng, Pan, and Ye Table 1. Demographic Characteristics, Clinical Manifestations, and Laboratory Measurements of the SLE Patients and Healthy Controls Characteristics Demographic characteristics Age (years) Male, n (%) Female, n (%) Clinical manifestations Lupus nephritis, n (%) Arthritis, n (%) Alopecia, n (%) Lupus headache, n (%) Skin rash, n (%) Oral ulcers, n (%) Fever, n (%) Laboratory measurements Anti-Sm, n (%) Anti-SSA/Ro, n (%) Anti-SSB/La, n (%) Anti-RNP, n (%) Anti-Rib P, n (%) Anti-dsDNA, n (%) Thrombocytopenia, n (%) Leukopenia, n (%) Hematuria, n (%) Proteinuria, n (%) C3↓ (
Decreased UBASH3A mRNA Expression Levels in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus Jie Liu,1,2 Jing Ni,1 Lian-Ju Li,1 Rui-Xue Leng,1 Hai-Feng Pan,1 and Dong-Qing Ye1,3
Abstract—Increasing evidence has demonstrated the association between UBASH3A gene and multiple autoimmune diseases (ADs). The aim of our study was to explore the potential effect of UBASH3A messenger RNA (mRNA) expression and its role in the pathogenesis of systemic lupus erythematosus (SLE). UBASH3A mRNA levels were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in total RNA, isolated from the peripheral blood mononuclear cells (PBMCs) of 32 SLE patients and 30 healthy donors with TRIzol Reagent. The expression level of UBASH3A mRNA was significantly reduced in PBMCs from SLE patients when compared with healthy controls (p = 0.002). UBASH3A mRNA expression levels in lower active SLE were significantly lower than that in inactive SLE groups (p =0.000). There was a negative association between mRNA levels of hyper-active and lower-active SLE patients (p = 0.000). Moreover, a significant negative correlation between UBASH3A mRNA expression and the onset age of SLE patients was found (p = 0.044). A negative correlation was found between UBASH3A mRNA expression and SLEDAI (p = 0.049). Nevertheless, no significant difference was found between patients with lupus nephritis (LN) and those without LN (p =0.392). The presence of leukopenia, positive for anti-dsDNA antibody and anti-SSB antibody were associated with UBASH3A mRNA levels in SLE patients (all p < 0.05). The dysregulation of UBASH3A mRNA levels in SLE patients and their correlations with experimental parameters suggested that UBASH3A may involve in the pathogenesis of SLE. KEY WORDS: UBASH3A; systemic lupus erythematosus; real-time reverse transcription-polymerase chain reaction; messenger RNA.
INTRODUCTION Systemic lupus erythematosus (SLE) is a complex, heterogenous autoimmune disease (AD) due to immunopathogenic abnormalities [1]. Immune dysregulation leads to excess production of autoantibodies and immune complex deposition, excess complement 1
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, People’s Republic of China 2 Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330029Jiangxi, People’s Republic of China 3 To whom correspondence should be addressed at Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, People’s Republic of China. E-mail: [email protected]
activation, and then immune damage to different organs and tissues [2]. The etiology of SLE is still incompletely understood. Genetic susceptibility and environmental factors have been reported to be involved in the initiation and promotion of this disease [3]. A combination of genome-wide association studies (GWAS) and casecontrol studies have identified more than 30 robust genetic susceptibility genes or loci in SLE [4–9]. However, the available risk variants explain only a small proportion of the predicted genetic heritability of SLE. Thus, the genetic basis of this disease remains to be elucidated. Proteins of the UBASH3/STS/TULA family recently recognized as potent regulators of cellular functions [10]. UBASH3A protein product contains interactive ubiquitinassociated (UBA) and Src-homology 3 (SH3) domains as well as a histidine phosphatase domain [11]. The
0360-3997/15/0000-0001/0 # 2015 Springer Science+Business Media New York
Liu, Ni, Li, Leng, Pan, and Ye UBASH3A gene is located on human chromosome 21q22.3, spans 40 kb and contains 15 exons [12]. UBASH3A is expressed predominantly in T cells suppressing T cell receptor signaling, underscoring antigen presentation to T cells as a key mechanism of disease pathogenesis [13]. Intriguingly, TULA-encoding (UBASH3A) alleles or phenotypes were found to be associated with some ADs [14–17]. For instance, UABSH3A was found to be associated with type 1 diabetes [18]. The discovery of UBASH3A as a novel susceptibility gene for human type 1 diabetes was confirmed by another study conducted in patients with Graves’ disease. Additionally, the UBASH3A rs3788013 polymorphism was shown to be associated with the presence of autoantibody to the thyroid peroxidase [17]. A statistically significant association between UBASH3A and generalized vitiligo was also observed [19]. Moreover, there was an association between UBASH3A and both rheumatoid arthritis and celiac disease for which epidemiological studies suggested the existence of a shared genetic background [20]. Collectively, these observations were in favor of an important role of UBASH3A in cellular regulation. Thus, the critical role of UBASH3A proteins in controlling T cell responses and, in regulation of T-cell-dependent findings in mouse experimental models showed that this protein may play a role in ADs [21, 22]. Although the association of UBASH3A gene polymorphisms with some autoimmune disease has been confirmed, messenger RNA (mRNA) expression levels of UBASH3A in patients with SLE remain unclear. In this study, we explored the mRNA expression levels of UBASH3A gene in PBMCs from patients with SLE and healthy controls. The association of SLE disease activity index (SLEDAI) scores and clinical data of SLE with the mRNA expression levels of UBASH3A were also analyzed.
MATERIALS AND METHODS Patient and Controls Thirty-two patients (30 women and 2 men, mean±SD age of 36.63±13.51 years, average SLEDAI 10.97±6.68) with SLE and 30 healthy controls (28 women and 2 men, mean±SD age of 32.03±9.61 years) with available RNA sample were performed by an analysis of mRNA for UBASH3A. The patients were recruited from the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital. All the patients were diagnosed in
accordance with the American College of Rheumatology (ACR) classification criteria revised in 1997 [23]. Sex- and age-matched controls were selected from healthy blood donors. Lupus nephritis (LN) was defined by the ACR criteria, i.e., according to any one of the following: persistent proteinuria (≥0.5 g/day) or the presence of active cellular casts, or biopsy evidence of LN [1]. Healthy controls were mainly recruited from the general population, healthy blood donors, and laboratory personnel. Healthy controls with no history of SLE, other inflammatory/ disease autoimmune, or cancer were recruited in our study. SLE disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 score [24]. The SLEDAI score was determined for each patient at the time of the blood draw. The SLEDAI was divided into three categories: patients were categorized as having hyper-active disease (scores >14), lower active disease (4 < SLEDAI score ≤ 14) or inactive disease (scores ≤4) based on the SLEDAI results [1]. The protocol for our study was consistent with the provisions of the World Medical Association Declaration of Helsinki. Peripheral bloods were obtained from the patients before they took any immunosuppressive drug, cytotoxic or glucocorticoid drugs. Real-Time Quantitative PCR PBMC blood samples obtained from SLE and healthy controls were prepared from EDTA-anticoagulated blood by Ficoll-Hypaque density gradient centrifugation. Total RNA was extracted from PBMCs by using TRIzol Reagent (Invitrogen life Technologies, Carlsbad, CA, USA) followed by RevertAid First Strand cDNA Synthesis Kit (Thermo Scientific, USA). RT-qPCR was performed to compare the mRNA expression of the UBASH3A gene (sense primer: 5′-GGACTTG-CACGACTAA-3′, antisense primer: 5′CCGTACGTCAATTGAC-3′). The assays were performed on ViiA™ 7 Real-Time PCR System (Applied Biosystems). Four microliters of cDNA (from a total 20μl reaction volume) was used in a 20-μl reaction. The RTqPCR reactions contained 10 μl TaqMan ® Gene Expression Master Mix, 1 μl Assay, and 5 μl H2O. Cycle conditions were as follows: pre-run for 2 min at 50 °C, incubation at 95 °C for 10 min, and 40 cycles of PCR at 95 °C for 15 s and at step 60 °C for 1 min. The RT-qPCR was run in duplicate, and the mRNA expression was determined by comparison with housekeeping gene β-actin from the same sample as internal control. Additionally, the relative expression levels were calculated using the 2−△△Ct method as described previously [25].
Decreased UBASH3A mRNA Levels in PBMCs from SLE Patients Collection of Clinical and Laboratory Data Clinical manifestations of SLE patients such as lupus nephritis, arthritis, skin rash, oral ulcers, and fever were recorded. Laboratory abnormalities , including thrombocytopenia (0.5 g/day), elevated erythrocyte sedimentation rate (ESR) (>20 mm/h), the presence of anti-Sm, anti-SSA, anti-SSB, anti-dsDNA, and serum levels of C3 and C4 were also retrieved from the medical record. Statistical Analysis Comparison of mRNA expression levels of UBASH3A between different groups were evaluated using the nonparametric Mann-Whitney U test. Quantitative variables were described using mean ± SD. Nonparametric distribution data were expressed as the median value and interquartile range (IQR). For the correlation analysis between UBASH3A mRNA levels and SLEDAI, Spearman’s rank correlation coefficient was used. A twosided p value of less than 0.05 was accepted as statistically significant. All calculations were analyzed by SPSS 11.5 software (SPSS Inc., USA).
RESULTS The demographic characteristics, clinical manifestations, and laboratory measurements of the SLE patients and healthy controls are shown in Table 1. The mean age of SLE patients was 36.63±13.51 years, and 93.75 % of them were women (Table 1). The mean age of healthy controls was 32.03±9.61 years, and 93.33 % of them were women. Clinical manifestations of SLE patients mainly included lupus nephritis (37.50 %), skin rash (34.38 %), fever (34.38 %), and arthritis (21.88 %). Experimental parameters of SLE patients were as follows in order of decreasing frequency: increased level of ESR (75.00 %), decreased level of C3 (68.75 %), the positive percentage of anti-SSA/ Ro (56.25 %), and anti-RNP (46.88 %). mRNA Expression of UBASH3A in PBMCs from SLE Patients and Healthy Controls The UBASH3A mRNA expression levels in PBMCs from 32 patients with SLE and 30 healthy subjects were analyzed by RT-qPCR. The data were normalized to housekeeping gene (β-actin). As shown in Table 2, the relative UBASH3A mRNA expression level was significantly
reduced in PBMCs from SLE patients when compared with healthy controls (p=0.002). In addition, UBASH3A mRNA levels in lower active SLE were significantly lower than that in inactive SLE groups (p=0.000). We also found a negative association between mRNA levels of hyperactive SLE and lower-active SLE patients (p = 0.000). Moreover, a significant negative correlation was found between UBASH3A mRNA expression and the age of onset in SLE patients (rs =−0.358, p=0.044) (Fig. 1). The mRNA expression was higher in patients with LN than that of those without LN, but no significant difference between the two groups was found (p=0.392). Association Between UBASH3A mRNA Expression Levels and SLEDAI or Clinical Data in SLE Patients We observed a negative correlation between UBASH3A mRNA expression and SLEDAI in SLE patients (rs =−0.350, p=0.049) (Fig. 2). We also analyzed the associations of UBASH3A mRNA levels with major laboratory and clinical parameters of SLE, and the results showed that the UBASH3A mRNA level were statistically significantly decreased in patients with leukopenia (p = 0.035) and anti-dsDNA antibody-positive group (p = 0.032). Additionally, the UBASH3A mRNA level was statistically significantly higher in the anti-SSB positive than that of anti-SSB antibody-negative group (p=0.016). However, no association of UBASH3A mRNA expression level with other clinical and laboratory parameters was found (Tables 3 and 4).
DISCUSSION SLE is a multiorgan autoimmune disease characterized by producing a large quantity of autoreactive antibodies, complements activation, and immune complex deposition, causing tissue and organ damage [26]. The pathogenesis of SLE is complex and includes genetic, environmental, and immunological factors. UBASH3A is characterized by a histidine as the essential residue in the active site, which could be added to the protein tyrosine phosphatase (PTP) superfamily [27]. UBASH3A expressed predominantly in T cells suppressing T cell receptor (TCR) signaling [21]. In addition, UBASH3A promote the dephosphorylation of the TCR signaling and function as a key negative regulator of TCR signaling [28]. Evidence of both B and T lymphocytes hyper-reactivity is typically found in AD [29]. Dysregulation of UBASH3A gene lowers the threshold of T cell activation and leads to
Liu, Ni, Li, Leng, Pan, and Ye Table 1. Demographic Characteristics, Clinical Manifestations, and Laboratory Measurements of the SLE Patients and Healthy Controls Characteristics Demographic characteristics Age (years) Male, n (%) Female, n (%) Clinical manifestations Lupus nephritis, n (%) Arthritis, n (%) Alopecia, n (%) Lupus headache, n (%) Skin rash, n (%) Oral ulcers, n (%) Fever, n (%) Laboratory measurements Anti-Sm, n (%) Anti-SSA/Ro, n (%) Anti-SSB/La, n (%) Anti-RNP, n (%) Anti-Rib P, n (%) Anti-dsDNA, n (%) Thrombocytopenia, n (%) Leukopenia, n (%) Hematuria, n (%) Proteinuria, n (%) C3↓ (
