1.Variation of RANKL/OPG in serum and T lymphocytes of patients with rheumatoid arthritis and their clinical significance
Chinese Journal of Rheumatology 2012;16(11):754-758
Objective To detect the positive expression level of CD3+ mRANK+ cells in the peripheral blood and the level of sRANKL and OPG in serum and culture supernatant of patients with rheumatoid arthritis (RA) and investigate the association between RANKL/RANK/OPG system and the destruction of RA.Methods Twenty-four RA patients and 20 healthy controls were collected in the Rheumatology and Immunology Department of the First Affiliated Hospital of Anhui Medical University.The peripheral blood mononuclear cell (PBMC) were extracted,subsequently stimulated in vitro with PHA for 72 hours.Flow cytometry (FCM) was used to detect the positive expression level of CD3+ mRANK+ cells in the peripheral blood,and ELISA was used to detect the level of sRANKL and OPG in serum and culture supernatant.Clinical and laboratory parameters were recorded.Multivariate linear regression and t-test were used to analyze the data from different groups.Results There was no statistical significant difference in the expression level of CD3+ mRANK+ cells [(14±4)% vs (15±7)%,P>0.05] in RA patients compared with that in healthy controls.Compared with healthy controls,the level of sRANKL [(133±49) vs (41 ±8) pmol/L,P<0.05],OPG [(390±154) vs (222±38) pg/ml,P<0.05] and sRANKL/OPG [(0.40 ±0.23) vs (0.19±0.05),P<0.05] increased in the serum of RA patients.The level of sRANKL [(34±19) vs (17±5) pmol/l,P<0.05] and sRANKL/OPG [(0.39±0.23) vs (0.19 ±0.05),P<0.05] increased in culture supernatant of RA patients.Multivariate linear regression showed that there was a negative correlation between DAS28 and the level of OPG in serum in RA ((β)=-0.681,t=3.315,P=0.005).There was a positive correlation between anti-CCP and sRANKL/OPG ratio inserum in RA((β)=0.497,t=2.326,P=0.040).There was a negative correlation between mRANKL and the Sharp method ((β)=0,522,t=2.370,P=0.032).There was a negative correlation between HAQ and the Sharp method ((β)=0.559,t=2.536,P=0.023).Conclusion Abnormality of RANKL shedding of T lymphocytes may be another inmmune machanism for the bone destruction of RA,The level of mRANKL expressed by activated T cell is a risk factor for the severity of bone damage of RA.In the bone destruction of RA,Anti-CCP antibody and RANKL/RANK/OPG system may be closely related.
2.Research progress on risk factors of osteoporotic fractures in patients with rheumatoid arthritis
Chinese Journal of General Practitioners 2016;(2):152-155,156
Rheumatoid arthritis is a autoimmune diseases characterized as joint chronic synovitis, and is accompanied with systemic damage.Osteoporotic fracture is one of the common complications of rheumatoid arthritis, which may decrease quality of life, and even increase the mortality of patients.Variety of factors may be associated with the occurrence of osteoporotic fractures in rheumatoid arthritis patients.In this article, through the literature review we discuss the risk factors of osteoporotic fracture, including vitamin D deficiency, lower limb muscle strength and balance ability in rheumatoid arthritis patients.
3.Relationship between the single nucleotide polymorphism of 5, 1O-methylenetetrahydrofolate reductase gene and the treatment of methotrexate in rheumatoid arthritis
Xiaomei ZHOU ; Jianhua XU ; Shengqian XU
Chinese Journal of Rheumatology 2008;12(9):598-602
Objective To investigate the single nucleotide polymorphism of 5,10-methylenetetrahy-drofolate reduetase gene and its association with the treatment of methotrexate in rheumatoid arthritis (RA).Methods A total of 184 patients with RA were divided into methotrexate (MTX) treatment group, MTX+other DMARDs treatment group, and treatment with other DMARDs but not MTX group. The clinical and laboratory data were evaluated before treatment and 24 weeks later. Efficacy and toxieities of each medication were also analyzed. Real-time fluorescent quantitative PCR was conducted to test gene mutations in RA patients and 100 healthy controls. Results There was no significant difference in the frenqueney of 677CC,CT, "IT and 1298AA, AC, CC between RA patients and the healthy controls. There was significant difference in the frenqueney of 677CC, CT, Tr between RA patients with cardiovascular eomplieations and the healthy controls. In the MTX treatment group, there was significant difference in the frenqueney of 1298AC, CC between the group in which MTX was effective and the other groups in which MTX was not effective, the occurrence rate of side effects of MTX in the patients with 677TT was higher than those without mutation(CC).In MTX+other DMARDs group, the occurrence rate of side effects of MTX in the patients with 677TT and CT was higher than that without mutation (CC). Conclusion There is no relationship between the pathogenesis of RA and the 677C/T, 1298A/C mutation of MTHFR gene. MTHFR gene 677C/T mutation is probably one of the genetic risk factors for cardiovascular complications of RA patients and the side effects of MTX. MTHFR gene 1298A/C allel is associated with the efficacy of MTX.
4.Difference of anti-cyclic citrullinated peptide antibody in patients with rheunmtoid arthritis in different age groups
Shengqian XV ; Li LIAN ; Jiahua XU
Clinical Medicine of China 2009;25(2):164-167
Objective To evaluate the clinical value of anti-cyclic citrullinated peptide (anti- CCP) anti-body in patients with rheumatoid arthritis(RA) in different agagroup.Methods Anti-CCP antibody was detected by ELISA in 220 cases of RA who were divided into three groups by onset age: juvenile group(n=24) ,adult group (n = 162) and older age group (n = 34).Results The ratio of anti-CCP in three groups were 14.3% (2/14), 81.7% (98/120) and 67.9% (19/28)(χ2 = 42.819, P <0.01).There was good coherence between the of anti-CCP and rheumatic factors (RF), with coherence coefficients of 71.4% (10/14 ), 82.2% (97/118) and 82.1% (23/28).Positive rank correlation was only found between anti-CCP and stages of X-rays(rs=0.243,P=0.002).Patients of juvenile group with anti-CCP were all present in poly-article subtype.There was a linear correlation be-tween anti-CCP and numbers of swollen joint, index of swollen joint in patients of juvenile group (r=0.563, P=0.045;r=0.574,P=0.040).The stage of both hand joints in older patients with anti-CCP positive was poorer than in those with anti-CCP negative[X-ray stage Ⅲ + Ⅳ was 52.2% (12/23), Ⅰ + Ⅱwas 0(0/9),χ2 =2.298,P =0.022].Conclusion The incidences of anti-CCP vary significantly among different age patients with RA.Anti-CCP in patients of juvenile group is related with poly-joint subtype, indicating the worsened swollen of joint.Anti-CCP in older age-onset patients with RA means the more severity of bone erosion.
5.The Significance of Detecting the Level of Plasma D-dimer in Systemic Lupus Erythematosus with Secondary Antiphospholipid Syndrome
Shuang LIU ; Yu WANG ; Shengqian XU
Journal of Medical Research 2006;0(04):-
Objective To investigate the significance of plasma D-dimer in systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome(APS). Methods The levels of plasma D-dimer in 104 SLE patients and 50 normal individuals were measured by immunoturbidimetry. Results The level of D-dimer in SLE was obvious higher than that in normal individuals(t=5.172,P0.05). Conclusion The level of plasma D-dimer in patients with SLE rised obviously. Its rise was associated with disease activity and secondary APS in SLE.
6.Hashimoto's thyroiditis accompanying with thyroid cancer:98 cases
Shengqian XU ; Zhiming SONG ; Guohua ZHU
Journal of Endocrine Surgery 2010;04(6):388-389,393
Objective To discuss the clinical characteristics of Hashimoto's thyroiditis accompanying with thyroid cancer. Methods Clinical data of 98 cases Hashimoto's thyroiditis accompanying with thyroid cancer were retrospectively reviewed. Results 2 cases underwent lateral thyroid lobectomy and isthmus resection. 58 cases underwent bilateral thyroid lobectomy. 35 cases underwent central lymph node dissection, with 15 cases of lymph node positive. 3 cases underwent modified radical dissection of cervical lymph nodes and all of them were proved to be lymph node positive. Metastasis rate is 25.0% and 52. 2% respectively for tumors whose diameter was less than 1 cm and greater than 1 cm. The difference has no statistic significance. Conclusions Hashimoto's thyroiditis usually accompany with thyroid papillary carcinoma and cervical lymph node metastasis can occur even if it's microcarcinoma. Lymph node metastasis rate increases with increasement of the tumor's diameter. Total thyroidectomy should be performed for Hashimoto's thyroiditis concomitant with thyroid cancer. And if necessary,lymph node dissection should be extended to the central region and lateral neck area.
7.Study of the FCRL5 gene single nucleotide p olymorphism in patients with ankylosing spondylitis
Tong LIU ; Shengqian XU ; Faming PAN ; Chen CHEN ; Jianhua XU
Chinese Journal of Rheumatology 2011;15(9):629-633
ObjectiveTo investigate the association between the FCRL5 gene (rs6427384 and rs12036228) single nucleotide polymorphism(SNP) and patients with ankylosing spondylitis (AS). Methods SNP of FCRL5 gene (rs6427384 and rs12036228) was analyzed in 169 patients with AS and 184 healthy controls by ligase detection reaction based on high temperature(LDR)-PCR. The distribution of FCRL5 genotypes and allele frequencies were detected between the two groups. Chi-square test, one-way ANOVA were used for statistical analysis. ResultsSignificant differences were found in the distribution of allele frequencies of FCRL5 gene between AS patients and health controls(P<0.05). The C allele frequencies of FCRL5 gene at positions of rs6427384 and rs12036228 were 17.3%, 92.3% and 25.0%, 87.2% respectively in the AS group and the control group. And the T allele frequencies of rs6427384 and rs12036228 were 82.7%, 7.7% and 75.0%, 12.8% in the AS group and the control group. The percentages of CC, CT and TT genotype(rs6427384) were 3.7%, 27.2%, and 69.1% in the AS group, which were significantly different from those of the control group(3.9%, 42.2% and 53.9% ) (x2=8.7637, P=0.0125 ). Staging of sacroiliitis in X ray were significantly different during AS patients whose genotype represented as CC, CT and TT (rs6427384)(x2=34.159, P=0.0001 ). Incidences of the initial symptoms (low back pain or inflammation of periphery joint)in the AS group were obviously differed among patients with different genotypes (rs6427384) (x2=7.254, P=0.027), so did the mean duration of morning stiffness (F=4.159, P=0.018) and the average scores of BASDAI (F=4.461, P=0.014). Incidences of the initial symptoms in the AS group were also conspicuously different between the AS patients with different genotypes (rs 12036228 ) (x2=6.640, P=0.036 ). ConclusionOur study suggests that the SNP(rs6427384 and rs12036228) of FCRL5 may be a susceptibility factor for AS in Anhui Han population and the genotype may influence the clinical phenotype of AS.
8.Study of the interleukin-1F7 gene single nucleotide polymorphism in patients with ankylosing spondylitis
Chen CHEN ; Shengqian XU ; Faming PAN ; Jianhua XU
Chinese Journal of Rheumatology 2011;15(8):546-549
Objective To investigate the association between interleukin(IL)-1F7 gene (rs3811047)single nucleotide polymorphism (SNP) and ankylosing spondylitis (AS). Methods SNP of IL-1F7 gene (rs3811047) was analyzed in 158 patients with AS and 181 healthy controls by ligase detection reaction based on high temperature ligase (LDR-PCR). The distribution of IL-1 F7 (rs3811047 ) genotypes and allele frequencies were detected between the two groups. Results Significant differences were found in the distribution of IL-1F7(rs3811047 ) genotypes and allele frequencies between AS patients and healthy controls. The frequency of A allele of IL-1F7 gene at positions rs3811047 was 12.03% and 17.68% in AS group and the control group,and the frequency of G allele was 87.97%, 82.32%, respectively (x2=4.2204, P=0.0399). The percentage of AA, AG and GG genotype was 0, 24.05%, 75.95% in AS group, which differed from the controls group (2.76%, 29.83%, 67.41% ). The difference had remarkable statistical significance (x2=6.2675, P=0.043).The positive rate of HLA-B27 in AS patients which represented as AG genotype was 70.27% (26/37),remarkably lower than that in AS patients which represented as GG genotype 94.23% (98/104), the difference was statistically significant (x2=2.168, P=0.030), erythrocyte sedimentation rate and C reactive protein levels were conspicuously lower than that in GG genotype (t=2.971, P=0.013; t=3.300, P=0.001 ). Conclusion Our study suggests that the SNP (rs3811047) of IL-1F7 may be a susceptibile factor for AS in Anhui Han population, the genotype may influence the clinical phenotypes of AS.Patients who carry the A allele may have less inflammation than patients who do not carry the A allele.
9.Correlation study between complement C3 level and degree of disease activity in patients with systemic lupus erythematosus
Xiaoli ZHANG ; Shengqian XU ; Jing CAI ; Shanyu CHEN ; Jianhua XU
Chinese Journal of General Practitioners 2016;15(5):375-378
Objective To investigate the relationship between complement C3 level and the degree of disease activity in patients with systemic lupus erythematosus(SLE).Methods A total of 1 012 patients with SLE were enrolled in this study from January 2006 to December 2013 at department of rheumatology and immunology,the first affiliated hospital of Anhui medical university.Serum complement C3 level was detected by rate erythenephelometry assay.The relationship between reduction of complement C3 and SLE was analyzed.Results Serum complement C3 clearly decreased in 782 patients,accounted for 77.27%.There were significant differences concerning serum complement C3 level among different groups of disease activity (F =131.275,P<0.01).The low serum complement C3 level was correlated with the high degree of disease activity (r =-0.517,P <0.01).Patients with SLE had a severe disease activity (SLE disease activity index ≥ 15) when the level of serum complement C3 was less than 0.57 g/L.Serum complement C3 levels were positively correlated with serum complement C4 (r =0.845,P < 0.01),peripheral blood leukocyte count (r =0.115,P < 0.01),hemoglobin (r =0.069,P < 0.01),platelet count (r =0.177,P <0.01) and albumin level (r =0.091,P < 0.01).There was also a negative association of serum complement C3 with 24 h urinary protein (r =-0.228,P < 0.01).101 patients whose average level of serum complement C3 was(0.48 ±0.26)g/L,were treated with glucocorticoid pulse therapy as high degree of disease activity.Conclusions There is a close relationship between serum complement C3 level and the degree of disease activity in SLE.Serum complement C3 less than 0.57 g/L might be seen in SLE with severe disease activity.
10.Clinical value of combined detection of anti-nuclear envelope protein antibody, anti-soluble acid resistant nucleoprotein and anti-mitochondrial antibody M2 subtype in diagnosis sjogren syndrome and primary biliary cirrhosis
Liping PENG ; Shengqian XU ; Hui XIAO ; Jing CAI ; Jianhua XU
Clinical Medicine of China 2015;31(1):42-46
Objective To investigate the clinical significance of anti-nuclear envelope protein antibody (gp210),anti-soluble acid resistant nucleoprotein (sp100) and anti-mitochondrial antibody M2 subtype (AMA-M2) in sjogren syndrome (SS) and primary biliary cirrhosis (PBC).Methods A total of 241 hospitalized patients diagnosed with connective tissue disease (CTD) were recruited.Anti-gp210,anti-sp100 and AMA-M2 were detected by indirect immunofluorescence.Results (1) Positive rate of AMA-M2,anti-sp100 and antigp210 in 241 cases CTD patient were 10.4% (25/241),3.3% (8/241) and 2.9% (7/241) respectively.(2) There were 16 cases with SS,5 cases with SS-PBC overlap syndrome and 17 cases with PBC in 241 patients with CTD.Distinction among groups of PBC,SS,SS overlapping PBC of positive incidence of AMA-M2 antibody (x2 =6.584,P =0.03) and anti-gp210 (x2 =8.735,P < 0.01) were significantly different,while there was no apparent difference about positive rate of anti-sp100 among the three groups (x2 =3.343,P =0.18).(3) Positive expression of either antibody of anti-gp210 or anti-sp100 in the three groups of SS,SS overlapping PBC,PBC were 3 cases,4 cases,4 cases respectively.The positive rates of any of three autoantibodies in three groups of were 8 cases,5 cases,13 cases respectively.(4) There were significant difference in terms of serum ALB(t =3.858,P<0.000 1),TSB(t =5.473,P<0.000 1),ALT(t =2.235,P=0.026),AKP(t =3.141,P =0.002) and γ-GT (t =2.317,P =0.021) in liver damaged patients of all CTD between AMA-M2 positive and negative patients (P < 0.05).However,serum TSB in anti-sp100 positive and negative patients were differed (t =7.892,P < 0.000 1).Serum AKP was different between anti-gp210 positive and negative patients (t =2.451,P =0.015).Conclusion Positive rate of anti-gp210,anti-sp100 and AMA-M2 are the highest in patients with SS overlap of the PBC among CTD patients.Combined detection can improve the sensitivity of diagnosis.Antisp100 and anti-gp210 are valuable for the diagnosis of SS-PBC overlaps syndrome with negative AMA-M2.