Ultraviolet B decreases DNA methylation level of CD4+ T cells in patients with systemic lupus erythematosus.

OBJECTIVE: In the present study, DNA methylation level of CD4+ T cells exposed to ultraviolet B (UVB) was investigated and its potential mechanisms were also explored. METHODS: CD4+ T cells from 12 cases of healthy subjects and 33 cases of SLE patients were isolated and exposed to different dosages (0, 50, 100 mJ/cm2) of UVB. Further, SLE patients were divided into two groups: active SLE group (22 cases, SLEDAI scores >4) and inactive SLE group (11 cases, SLEDAI scores ≤4). DNA methylation was evaluated by the Methylamp™ Global DNA Methylation Quantification Ultra Kit. The mRNA and protein expression levels of DNA methyltransferases (DNMT1 and DNMT3A) were detected by real-time PCR and western blot, respectively. RESULTS: The levels of DNA methylation and DNMT3A mRNA in SLE patients were significantly decreased compared with those in healthy subjects at baseline. After different dosages of ultraviolet irradiation (0, 50 and 100 mJ/cm2), DNA methylation levels of CD4+ T cells were all reduced in a dose-dependent manner in three subgroups. Additionally, 100 mJ/cm2 ultraviolet irradiation in active SLE group contributed to a significant decrease of both DNA methylation and DNMT3A mRNA levels in CD4+ T cells. UVB exposure had no significant effects on expression levels of DNMT1 mRNA and protein and DNMT3A protein. CONCLUSION: UVB decreases DNA methylation level of CD4+ T cells in SLE patients probably via inhibiting DNMT3A mRNA expression level, which needs to be further explored.

Association of Fas gene polymorphisms with systemic lupus erythematosus: a meta-analysis.

The Fas gene polymorphisms -670A/G (rs1800682) and -1377G/A (rs2234767) have been shown to be associated with systemic lupus erythematosus (SLE), but findings are not consistent. To clarify this point, a meta-analysis was performed. We searched PubMed, CNKI, CBM and Wanfang database. Meta-odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to combine the data by fixed/random effects models based on heterogeneity test. The statistical analyses were conducted using Stata software. A total of seven studies involving 759 cases and 820 controls were considered in this study and ethnicity-specific meta-analysis was performed on Caucasian and Asian population. In overall population, meta-analysis revealed a trend toward to an association between SLE and Fas -670 A allele (OR = 1.310, 95 %CI = 1.028 ~ 1.670, P = 0.029). Similar results were detected in recessive model (OR = 1.626, 95 %CI = 1.104 ~ 2.395, P = 0.014) and in homozygous genotypic contrast (OR = 1.728, 95 %CI = 1.049 ~ 2.848, P = 0.032). Stratification by ethnicity indicated a significant association between SLE and the Fas -670A/G polymorphism in Asian population when allelic contrast (OR = 1.331, 95 %CI = 1.066 ~ 1.662, P = 0.011), homozygous genotypic contrast (OR = 1.848, 95 %CI = 1.164 ~ 2.932, P = 0.009) and dominant model were performed (OR = 1.542, 95 %CI = 1.045 ~ 2.275, P = 0.029). Meta-analysis of the Fas -1377G/A polymorphism indicated a significant association between SLE and the G allele in overall population (OR = 1.277, 95 %CI = 1.004 ~ 1.624, P = 0.046). The results from this meta-analysis provide evidence for the association between the Fas -670A/G and -1377G/A polymorphism and the risk of SLE. However, further studies are needed to draw a definitive conclusion.

[Peptidyl arginine deiminase 4 participates in the pathogenesis of rheumatoid arthritis by influencing histone methylation].

OBJECTIVE: To explore the probable function of peptidyl arginine deiminase 4 (PAD4) in rheumatoid arthritis(RA). METHODS: Real-time quantitative polymerase chain reaction (PCR) was used to determine the expression of PAD4 mRNA in peripheral blood mononucleated cells (PBMCs) from 60 RA patients and 40 healthy individuals. Asymmetric di-methylation of histone H3R17, symmetric di-methylation and mono-methylation of H4R3 were semi-quantified by Western blotting in 12 patients with osteoarthritis (OA), 26 patients with RA and 10 healthy controls. RESULTS: PAD4 mRNA in RA was significantly higher than that in healthy controls[34.6(16.7, 70.8) vs 20.6(11.1, 51.8), P < 0.05]. The level of histone H3R17 asymmetric di-methylation in RA was significantly higher than that of OA or control groups (71.34 ± 25.65 vs 37.18 ± 18.62 vs 50.67 ± 13.99, P < 0.01) , which was positively related to Tender joint count and Swollen joint count in 28 joints (r = 0.418, P = 0.034;r = 0.402, P = 0.042). The level of histone H4R3 symmetric di-methylation was similar in RA,OA and control groups (75.02 ± 20.35 vs 57.92 ± 22.77 vs 68.37 ± 17.57, P > 0.05) . The level of histone H4R3 mono-methylation in RA patients was significantly lower than that of OA patients and healthy individuals (11.24 ± 7.81 vs 32.77 ± 30.77 vs 51.20 ± 47.14, P < 0.05). The level of histone H4R3 mono-methylation in RA patients was negatively correlated to PAD4 (r = -0.643, P < 0.01) . The level of histone H3R17 asymmetric di-methylation and H4R3 symmetric di-methylation was not associated with PAD4 level in RA group (r = -0.185, P = 0.377; r = 0.198, P = 0.344). CONCLUSIONS: The level of histone H3R17 asymmetric di-methylation is significantly higher and the level of histone H4R3 mono-methylation is significantly lower in RA patients comparing with OA and control groups. Abnormality of histone methylation may be one of the mechanisms for the development of RA. PAD4 probably plays an important role in rheumatoid arthritis by influencing histone methylation.

[Activation of hypomethylated DNA on plasmacytoid dendritic cells in patients with systemic lupus erythematosus].

OBJECTIVE: To explore the activation of hypomethylated DNA on plasmacytoid dendritic cells (pDC) in patients with systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of SLE patients and healthy controls. The methylation level of DNA and the expression of DNA methyltransferase 1 (DNMT1) mRNA were detected. Flow cytometry was used to detect the expression of CD32 on pDC and the serum concentration of interferon-alpha (IFN-α) measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The DNA methylation level from SLE patients (1.4 ± 0.6) % was lower than that of controls (1.8 ± 0.7) % (P < 0.01). The expression of DNMT1 mRNA significantly decreased in SLE patients (0.06 ± 0.03) versus the controls (0.09 ± 0.02) (P < 0.01). The CD32 expression on pDC from SLE patients (29 ± 19)% was higher than that from controls (18.02 ± 7.80)% (P < 0.01). The serum level of IFN-α in SLE patients (4.5 ± 6.7) ng/L was significantly higher than that of controls (2.1 ± 2.0) ng/L (P < 0.01). The methylation level of DNA in SLE patients was positively correlated with the expression of DNMT1 mRNA (r = 0.257, P < 0.05) and negatively with the expression of CD32 (r = -0.358, P < 0.01) and IFN-α (r = -0.280, P < 0.05). CONCLUSIONS: The methylation level of genomic DNA decreases in SLE patients due to the down-regulated expression of DNMT1 gene. Hypomethylated DNA may be translocated intracellularly via endocytic receptor (CD32) on pDC. And the activation of pDC is induced to produce IFN-α so as to participate in the onset of SLE.

[Role of transcription factor ETS-1 and B cell in the pathogenesis of systemic lupus erythematosus].

OBJECTIVE: To explore the effects of transcription factor ETS-1 mRNA and B lymphocyte-associated cytokines on the differentiation of B cells in systemic lupus erythematosus (SLE) patients and explore its pathogenic and clinical significance. METHODS: Thirty-one SLE patients (20 active and 11 inactive) and 15 healthy controls were enrolled. CD19+ B cells were isolated with magnetic beads. The levels of ETS-1 mRNA in B cells were determined by real-time polymerase chain reaction (PCR). Flow cytometry was used to detect the altered ratio of CD19-CD138 + plasma cells and CD19 + B cells. And enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum levels of B cell differentiation-related cytokines interleukin-10 (IL-10) and APRIL. RESULTS: Compared to the healthy controls, SLE patients showed decreased mRNA expression level of ETS-1 in B cells (Z = -4.218, P < 0.01) . Moreover, the expression level of ETS-1 mRNA was significantly negatively correlated with the proportion of CD19-CD138+ plasma cells (r = -0.359, P < 0.05) and negatively correlated with the CD19-CD138 +B cells/CD19+ plasma cells ratio (r = -0.493, P < 0.01) . However, there was no correlation in normal controls. Significant negative correlation existed between the expression level of ETS-1 mRNA in B cells and the serum levels of IL-10 and APRIL in active SLE patients. But no correlation existed in inactive group. CONCLUSION: ETS-1 may participate in the pathogenesis of SLE through its effects on the differentiation of B cells and cooperation with IL-10 and APRIL.

[Predictive factors and unfavorable prognostic factorial analysis of interstitial lung disease in patients with inflammatory myopathy].

OBJECTIVE: To explore the clinical features, predictive factors and unfavourable prognostic factors of interstitial lung disease (ILD) in the patients with polymyositis and dermatomyositis (PM/DM) so as to provide rationales for early clinical diagnosis and treatment. METHODS: The medical records of 244 PM/DM patients from Department of Rheumatology & Immunology of Anhui Medical University Affiliated Provincial Hospital from August 2001 to August 2011 were reviewed to analyze the clinical features, predictive factors and unfavourable prognostic factors of ILD in PM/DM patients. RESULTS: The major clinical manifestations of PM/DM-ILD included dry cough, chest tightness and shortness of breath during activities and Velcro rale in lower lung. Besides anti-Jo-1 antibody, multivariate unconditional Logistic regression analysis indicated that amyopathic dermatomyositis (ADM), arthralgia/arthritis, fever and Gottron's sign were the predictive factors for the development of ILD in PM/DM patients. ADM and Hamman-Rich-like pattern ILD were the poor prognostic factors while large dose glucocorticoids plus immunosuppressant therapy in the early time was a protective factor for PM/DM-ILD patients. CONCLUSION: Some clinical features are the predictive factors for the development of ILD. ADM and Hamman-Rich-like pattern ILD are poor prognostic factors. Large dose glucocorticoids plus immunosuppressant therapy can significantly improve the prognosis of PM/DM patients.

The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis.

The aryl hydrocarbon receptor (AHR) signaling pathway participates in immune regulation of multiple autoimmune diseases, including rheumatoid arthritis (RA). We conducted this study to investigate the association of AHR signaling pathway genes (AHR, ARNT, AHRR) single nucleotide polymorphisms (SNPs), as well as their methylation levels, with RA susceptibility. Nine SNPs (AHR gene rs2066853, rs2158041, rs2282885, ARNT gene rs10847, rs1889740, rs11204735, AHRR gene rs2292596, rs2672725, rs349583) were genotyped via improved multiple ligase detection reaction (iMLDR) in 479 RA patients and 496 healthy controls. We used the Illumina Hiseq platform to detect methylation levels of these genes in 122 RA patients and 123 healthy controls. A significant increase in rs11204735 C allele frequency was observed in RA patients when compared to controls. Further, rs11204735 polymorphism was associated with a decreased risk of RA under the dominant model. ARNT CCC haplotype frequency was significantly increased in RA patients in comparison to controls. In the AHRR gene, rs2672725 GG genotype, G allele frequencies were significantly related to an increased risk of RA and rs2292596, rs2672725 polymorphism were significantly associated with an increased risk of RA under the dominant model, recessive model, respectively. However, no significant association was identified between AHR gene polymorphism and RA susceptibility. The AHR methylation level in RA patients was significantly higher than the controls, while AHRR methylation level was abnormally reduced in RA patients. In addition, AHRR rs2672725 genotype distribution was significantly associated with the AHRR methylation level among RA patients. In summary, ARNT rs11204735, AHRR rs2292596, and rs2672725 polymorphisms were associated with RA susceptibility and altered AHR, AHRR methylation levels were related to the risk of RA.

[The significance of serum peptidylarginine deiminase 4 in rheumatoid arthritis].

OBJECTIVE: To detect the levels of serum peptidylarginine deiminase (PADI)4 and explore its significance in rheumatoid arthritis (RA). METHODS: The presence of PADI4, anti-PADI4 antibodies and anti-cyclic citrullinated peptide (CCP) antibodies levels were examined by enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 100 patients with RA, 23 patients with other rheumatic diseases, and 24 healthy controls. The associations between PADI4 and the disease activity score using 28 joint counts (DAS28) score, anti-CCP antibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PADI4-94 (rs 2240340) and PADI-104 (rs 1748033) gene polymorphisms and other indexes were analyzed in RA. RESULTS: The levels of PADI4 in RA patients were significantly higher than in other rheumatic diseases and healthy controls (F = 8.75, P < 0.001). There was no significantly difference in levels of PADI4 among ADI4-94 (rs 2240340)/PADI-104 (rs 1748033) genotypes. CONCLUSIONS: PADI4 is associated with disease activity involved in the RA pathogenesis and may be a RA pathogenic antigen.

Expression profile of PU.1 in CD4+T cells from patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. PU.1 is an important member of the ETS transcription factors family which has diverse functions such as regulating the proliferation, differentiation of immune cells and multiple inflammatory cytokines. Previous studies preliminary explored the relation between PU.1 and SLE. To further explain the potential role of PU.1 in the pathogenesis of SLE, 40 SLE patients and 20 age-sex matched healthy controls (HC) were recruited in this study. Flow cytometry was used to test the percentages of CD4+PU.1+T cells in peripheral blood mononuclear cells (PBMCs) from patients with SLE and HC. Expression levels of PU.1 mRNA in CD4+T cells from SLE patients and HC were analyzed by real-time transcription-polymerase chain reaction. Expression levels of plasma IL-1ß, IL-9, IL-18, IL-6, IFN-α, TNF-α, IL-10 and TGF-ß1 were measured by enzyme-linked immunosorbent assay. The percentage of CD4+PU.1+T cells in PBMCs from patients with SLE was significantly higher than that from HC (P < 0.001). In addition, the PU.1 mRNA expression in CD4+T cells from SLE patients was increased than that from HC (P = 0.002). In SLE patients, no significant correlation was found between the percentage of CD4+PU.1+T cells and the expression of PU.1 mRNA in CD4+T cells (P > 0.05). Associations of PU.1 mRNA expression in CD4+T cells with major clinical and laboratory parameters of SLE patients were also analyzed, but no significant correlations were found. Consistent with previous studies, SLE patients had increased IL-1ß, IL-18, IL-6, IFN-α, TNF-α and IL-10 plasma concentrations than HC (P < 0.01). The expression level of plasma TGF-ß1 was significantly decreased in SLE patients than in HC (P < 0.001). In SLE patients, the expression level of IL-1ß was positive correlated with PU.1 mRNA expression in CD4+T cells (P = 0.001). Our study first time evaluated the expression profile of PU.1 in CD4+T cells from SLE patients confirming that PU.1 may participate in the pathogenesis of SLE.

[Comparison and clinical significance between geometrical characteristics of tibial plateau between Uighur nationality and Han people].

OBJECTIVE: To compare the difference and clinical significance of geometrical characteristics of tibial plateau between Uighur nationality and Han people by computed tomography scan and three-dimensional reconstruction. METHODS: A total of 49 inpatients and outpatients were randomly selected (normal knee without any tibial involvement) and volunteers of Han people and 45 ones of the Uighur nationality at our hospital and cooperative hospitals. Then the subjects were divided into groups according to gender. The following linear geometric parameters of tibial plateau were measured: width of tibial plateau (WTP), width of medial tibial plateau (WMTP), sagittal length of medial tibial plateau (SLMTP), width of lateral tibial plateau (WLTP) and sagittal length of lateral tibial plateau (SLLTP). RESULTS: (1) Males were greater than females in linear parameters in the same group (P < 0.01); (2) the groups of Uighur nationality were greater than groups of Han people in linear parameters in the same gender (P < 0.05); (3) the gaps between WMTP and WLTP, SLMTP and SLLTP of Uighur nationality were all more approximate than those of Han people (P < 0.05). CONCLUSION: The geometrical characteristics of tibial plateau have some visible discrepancy between Uighur nationality and Chinese Han people. The prosthetic design concept and technology of total knee replacement targeting the Uighur nationality should take into consideration the discrepancy.

Injection of CD40 DNA vaccine ameliorates the autoimmune pathology of non-obese diabetic mice with Sjögren's syndrome.

BACKGROUND: Overexpression of CD40 has been reported in patients with primary Sjögren's syndrome (pSS). The increased CD40 expression promote autoimmune response and enhance inflammation in pSS. The aim of this study is to block CD40-CD154 interaction with CD40 DNA vaccine to slow the disease progression of SS in non-obese diabetic (NOD) mice. METHODS: Female NOD mice were treated with CD40 DNA vaccine, empty vector and normal saline. The salivary flow rate was measured, whereas lymphocytes infiltration in the salivary glands was assessed by histopathology. Expression of CD40 and B220 in salivary were examined by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. CD40, IL-1ß, TNF-α and IL-6 levels in the salivary glands were detected by PCR. Serum anti-CD40 antibody was measured by ELISA. Serum anti-nuclear antibody (ANA) was monitored by immunofluorescence. RESULTS: NOD mice treated with CD40 DNA vaccine showed higher levels of anti-CD40 antibody compared with the controls. The expression of CD40 in the salivary glands of NOD mice in CD40 DNA vaccine group was decreased. The infiltration of lymphocytes was reduced in the salivary glands and saliva secretion was increased in the treatment group. The expression level of TNF-α and IL-6 in salivary glands were declined. The splenic dendritic cell and plasma cell populations were reduced and the level of ANA was decreased in NOD mice with CD40 DNA vaccine treatment. CONCLUSIONS: CD40 DNA vaccine inhibits the immune response and reduce inflammation in epithelial tissues SS in non-obese diabetic (NOD) mice, suggesting that CD40 DNA vaccine could be a new therapeutic approach in treatment of pSS.

[Expression of FOXP3 in CD4+ CD39+ T cells of patients with systemic lupus erythematosus and dynamic observation of treatment with glucocorticoid].

OBJECTIVE: To investigate the level of FOXP3 expressed in CD4+ CD39+ T cells in peripheral blood of patients with systemic lupus erythematosus (SLE) and observe the regulation of glucocorticoid on it. METHODS: Frequencies of CD4+ CD25+ CD39+, CD4 CD25+ FOXP3+ and CD4+ CD39+ FOXP3+ T cells and levels of FOXP3 protein were analyzed by flow cytometry of 47 SLE patients (including 29 untreated/active SLE) and 22 healthy controls. Meanwhile, correlations among three groups and influences of glucocorticoid were analyzed. RESULTS: Percents of CD4+ CD25+ CD39+ T cells expressed in active SLE, inactive SLE and healthy controls were (1.3 +/- 0.5)%, (1.9 +/- 0.8)% and (2.3 +/- 1.0)% respectively, the level decreased in active SLE compared with inactive SLE and healthy controls P < 0.05 in each group, but it had no significant difference between the latter two groups (P > 0.05). In active SLE, levels of FOXP3 protein expressed in CD4+ CD25+, CD4+ CD25high and CD4+ CD39+ T cells were (45 +/- 12)%, (65 +/- 14)% and (70 +/- 14)% respectively. Levels of FOXP3 expressed in CD4+ CD25high and CD4+ CD39+ T cells were higher than that expressed in CD4+ CD25+ T cells (P < 0.01), while it had no significant difference between CD4 CD25high T cells and CD4+ CD39+ T cells (P > 0.05). CONCLUSIONS: These results demonstrate that CD39 may be a better surface marker of regulatory T cells, and that deficiency of CD39+ Treg cells may play an important role in the pathogenesis of SLE.

[Expression of forkhead box protein P3 in peripheral blood and salivary gland of patients with Sjogren's syndrome].

OBJECTIVE: To investigate the expression of forkhead box protein P3 (Foxp3) in the peripheral blood and salivary gland of patients with Sjogren's Syndrome (SS). METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine Foxp3mRNA expression in the CD(4)(+) T cells and the salivary glands from 6 primary SS patients and 6 normal controls. Serial sections of biopsied salivary gland (SG) were examined with immunohistochemistry, using monoclonal mouse anti-human CD(4) and Foxp3 in 6 healthy controls and 31 primary SS patients. RESULTS: Significant difference in the number of infiltrating CD(4)(+) T cells was noted in the salivary glands of the patients and controls, but Foxp3(+)CD(4)(+) T cells were almost absent in those biopsy samples. Foxp3mRNA expression in the blood of SS patients was significantly lower than that in normal controls (0.21 +/- 0.17 vs 1.32 +/- 0.38, P < 0.0184). Foxp3mRNA expression was not detectable in the tissue of the salivary glands (n = 6). CONCLUSION: The absence of Foxp3(+)CD(4)(+) T cells in salivary glands with reduction of Foxp3mRNA expression in peripheral blood suggests an important role of Foxp3 in the pathogenesis of SS.

[Immunopathology of labial glands of patients with primary Sjögren's syndrome].

OBJECTIVE: To investigate the expression of CD4+CD25+ regulatory T cell (Treg) in labial gland (SG) of the patients with Sjögren's syndrome (SS). METHODS: Specimens of labial gland were obtained from 25 primary SS patients and 6 healthy controls during biopsy to be made into serial sections. Immunohistochemistry was used to examine the expression of CD25, CD4, CD8, CD68 and Foxp3. RESULTS: Infiltration of a great amount of mononuclear cells and atrophy of part of the labial glands were seen in the specimens from SS patients. The percentage of CD4+ T cells in the infiltrating leucocytes of the SS patients was (44.2 +/- 20.5)%, significantly higher than that of the controls [(9.2 +/- 6.0)%, P < 0.01]. CD25 and Foxp3 were completely absent in the specimens from both the controls and SS patients. CONCLUSION: CD4+CD25+ regulatory T cell lacks in the labial gland of SS patients. CD4+CD25+ regulatory T cells play a key role in the progression of SS.

[Expression of CD4+ CD25+ regulatory T cells in peripheral blood and salivary gland of patients with primary Sjögren's syndrome].

OBJECTIVE: To investigate the expression of CD(4)(+) CD(25)(+) regulatory T cells (Tregs) in the peripheral blood and salivary gland of patients with primary Sjögren's syndrome (pSS). METHODS: Samples of peripheral venous blood were collected from 57 newly diagnosed pSS patients, 1 male and 56 females, aged 47 (20 approximately 76), and 46 healthy controls. The levels of CD(4)(+) CD(25)(+) T regulatory cells and CD(4)(+) CD(25)(high) T regulatory cells in the peripheral blood were measured by flow-cytometric assay. Biopsy specimens of labial gland were collected from the 57 patients and 6 healthy person or patients with labial gland cyst. Pathological examination was conducted by light microscopy. Immunohistochemistry was conducted, by using monoclonal mouse anti-human to detect the expression of CD25, CD4, CD8, and CD68. Western blotting was used to detect the levels of IgG, IgM, and IgA. The salivary flow rate was measured. Schirmer's test was used to measure the tear flow rate. RESULTS: The level of CD(4)(+) CD(25)(+) Tregs in the blood of pSS patients was 6.9% (2.84% - 13.50%), significantly lower than that of the healthy controls [10.9% (5.77% - 15.3%), P < 0.001). The level of CD(4)(+) CD(25)(high) Tregs the blood of pSS patients was 0.6% (0.001% - 1.83%), significantly lower than that of the healthy controls [1.1% (0.13% - 2.45%), P < 0.001]. Immunohistochemistry showed that most of the infiltrating lymphocytes in the labial gland of the pSS patients were CD(4)(+) T cells, and there was no CD(25)(+) T cell in both groups. The numbers of peripheral CD(4)(+) CD(25)(+) T cells and CD(4)(+) CD(25)(high) Tregs in the pSS patients were not correlated with the tear flow rate, salivary flow rate, anti-SS-A/SS-B antibodies, and immunoglobulin level. CONCLUSION: The pSS patients show an absence of CD(4)(+) CD(25)(+) T cell in the labial gland of pSS patients, and reduction of the numbers of CD(4)(+) CD(25)(+) and CD(4)(+) CD(25)(high) Tregs in the peripheral blood, which suggests that Tregs play an important role in the pathogenesis of salivary gland destruction in SS.

Genetic association of aromatic hydrocarbon receptor and its repressor gene polymorphisms with risk of rheumatoid arthritis in Han Chinese populations.

The goal of this study was to evaluate the potential relationship among polymorphisms of aromatic hydrocarbon receptor, aromatic hydrocarbon receptor repressor, and rheumatoid arthritis (RA) susceptibility as well as the association among the polymorphisms of aromatic hydrocarbon receptor, aromatic hydrocarbon receptor repressor, and their expression.We performed a hospital-based, case-control study of 400 patients with RA and 726 healthy controls in Han Chinese populations. Two single-nucleotide polymorphisms were selected for genotyping including aromatic hydrocarbon receptor (rs2066853) and aromatic hydrocarbon receptor repressor (rs2292596).To single-nucleotide polymorphism rs2292596, a statistically significantly increased risk of RA was found to be associated with the G allele of rs2292596; the odds ratio was 2.170 (95% confidence interval: 1.820-2.587). Unfortunately, no significant differences exhibited in the allelic and the genotype frequencies of rs2066853 between 2 groups. We failed to find any association between rs2066853, rs2292596 genotypes and their expression of patients, respectively. No statistical relationship was found between aromatic hydrocarbon receptor, aromatic hydrocarbon receptor repressor at messenger Ribonucleic acid levels and clinical data, either.This study demonstrated that the polymorphisms of rs2292596 was significant with genetic susceptibility to RA patients; furthermore, it suggests the G allele of rs2292596 might be associated with a dangerous effect on RA in Han Chinese populations.

Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of rheumatoid arthritis.

OBJECTIVE: The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of patients with rheumatoid arthritis. METHODS: Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+CD4+T, CD4+CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. RESULTS: The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23±10.71)% vs. (18.83±7.32)%, p<0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71±1.63) vs. (2.00±1.27), p=0.002; (2.62±2.08) vs. (0.62±0.29), p<0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90 (6.10±80.10)% vs. (52.49±19.18)%, p<0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, X2=24.03, p<0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs [(46.02±14.68)% vs. 17.90 (6.10±80.10)% vs. (34.22±10.33)%, X2=38.29, p<0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+CD25+T cells. CONCLUSION: AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.