Shengqian Xu

Gender and age influence on clinical and laboratory features in Chinese patients with systemic lupus erythematosus: 1,790 cases

This study aims to review the cumulative clinical and laboratory data of 1,790 Chinese patients with systemic lupus erythematosus. Data were compared separately between male and female patients for each disease onset age groups and among three disease onset age groups in male and female patients. The ratio of female to male was 9.2:1, with differences among three age groups. There was no difference in mean age at onset between females and males. But diagnosis delay in male patients is shorter than in females. When compared with females, in adult-onset patients, males presented more frequently with serositis, pleuritis and discoid rash, but less frequently with malar rash, alopecia, oral ulcers, elevated erythrocyte sedimentation rate, anti-nuclear, anti-SSA and anti-SSB antibodies. In younger-onset group, males have less discoid rash. In older-onset group, males have less anti-SSA antibodies. In male patients, only anti-SSB antibodies were different in three age groups and negatively correlate to age. Among female patients, age had negative correlations with malar rash, discoid rash, photosensitivity, anti-dsDNA, anti-Sm, anti-SSB and anti-rRNP antibodies, but positive correlation with leucopenia. We conclude that women of childbearing age possess a distinct clinical and laboratory profile. In addition, differences in disease manifestations seem to be correlated with female sex hormones rather than age.

Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokines and bone loss in patients with rheumatoid arthritis

OBJECTIVE The aim of this study was to describe the associations between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity, inflammatory cytokines and bone loss/erosions in patients with RA. METHODS The study included 130 patients with RA and 80 healthy controls. Serum 25(OH)D, IL-17 and IL-23 levels were detected by ELISA. Radiographic bone erosion was assessed using the van der Heijde modified Sharp score and BMD was measured using DXA. RESULTS There were no significant differences in age, gender and BMI between the RA and control groups. Serum level of 25(OH)D was markedly lower in the RA group than in the control group [43.12 nmol/l (s.d. 15.59) vs 57.93 (15.95), P < 0.01]. In RA patients, 25(OH)D levels were significantly and negatively associated with clinical parameters of disease activity including swollen joint count, tender joint count, joint pain degree, morning stiffness time and HAQ score and laboratory measures including platelets and ESR after adjustment for gender, age and BMI. They were also negatively associated with serum levels of IL-17 and IL-23. While 25(OH)D levels were not associated with radiographic bone erosions of RA, they were significantly lower in those with osteopenia and osteoporosis than in those with normal BMD (P < 0.01). CONCLUSION 25(OH)D levels were reduced in patients with RA and were negatively associated with disease activity, IL-17/IL-23 and bone loss in RA. These suggest that vitamin D deficiency may play a role in the aetiology of RA.

Oral administration of type II collagen suppresses pro-inflammatory mediator production by synoviocytes in rats with adjuvant arthritis

The objective of this study was to investigate the effect of the oral administration of type II collagen (CII) on pro‐inflammatory mediator production by synoviocytes in rats with adjuvant arthritis (AA). Sprague‐Dawley rats were fed with bovine CII either before immunization with Complete Freunds adjuvant (CFA) or after initiation of arthritis. Hind paw secondary swelling was measured and synoviocytes were harvested. Sera from portal vein of oral tolerized rats were collected and in vitro synoviocytes culture or synoviocytes‐Peyers Patches (PP) cells coculture system were developed. Interleukin (IL)‐1 activity was measured by a mouse thymocyte activation assayed by MTT dye reduction and tumour necrosis factor (TNF) activity was measured by an L929 cytotoxicity bioassay. Nitric oxide (NO) and malondialdehyde (MDA) levels were measured by biochemical methods. We found that feeding with CII (5, 50 and 500 µg/kg) for 7 days before immunization significantly suppressed hind paw secondary swelling measured at day 16, 20, 24 and 28 (all P < 0·01) and pro‐inflammatory mediator (IL‐1, TNF, NO and MDA) production by synoviocytes (all P < 0·01) in rats with AA. Feeding with CII (5, 50 and 500 µg/kg) for 7 days after initiation of arthritis had a similar effect. CII (1, 10, 100 µg/ml) had no effect on IL‐1 and TNF production by synoviocytes in vitro, but CII 10 µg/ml suppressed IL‐1 and TNF production by synoviocytes‐PP cells coculture system (P < 0·01), which was antagonized by anti‐TGF‐β antibody (10 µg/ml) (P < 0·01). Portal serum (1 : 10) from oral tolerized rats suppressed IL‐1 and TNF production by synoviocytes (P < 0·01), which was also antagonized by anti‐TGF‐β antibody (10 µg/ml) (P < 0·01). We conclude that oral administration of CII had prophylactic and therapeutic effects on AA and over‐production of IL‐1, TNF, NO and MDA by synoviocytes was suppressed. Bystander active suppression may be the main mechanism of oral CII in the suppression of synoviocyte function.

Associations of the IL-1F7 gene polymorphisms with rheumatoid arthritis in Chinese Han population

Our aim was to investigate whether genetic polymorphism of IL‐1F7 (rs3811047) was involved in the susceptibility to rheumatoid arthritis (RA) in Chinese Han population. Single nucleotide polymorphism (SNP) of IL‐1F7 gene (rs3811047) was analyzed in 184 unrelated Chinese Han patients with RA and 184 healthy controls by ligase detection reaction based on high temperature ligase detection reactions polymerase chain reaction (LDR‐PCR). There were no statistically significant differences in the genetic polymorphism (genotypes and allele frequencies) of IL‐1F7 (rs3811047) in the patients with RA compared with control. Although all of the clinical and laboratory measures were similar to each other among patients with different genotypes, RA patients carrying AA or AG genotypes had lower swollen joint count, swollen joint index, rest pain and health assessment questionnaire (HAQ) score than that in patients having GG genotype (P < 0.05). These findings show that no evidence for the involvement of a pro‐inflammatory polymorphism in the IL‐1F7 in the susceptibility to RA in China. Patients carrying A allele had less severe disease activity than those not carrying this allele, suggesting that the A allele of IL‐1F7 gene (rs3811047) may have a protective effect on RA.

Male Sexual Dysfunction and Ankylosing Spondylitis: A Systematic Review and Metaanalysis

Objective. No consensus has been reached on sexual dysfunction in men with ankylosing spondylitis (AS). Our study aimed to derive a more precise estimation of the sexual function and its clinical correlations in men with AS. Methods. A metaanalysis was performed and the related literature were searched in PubMed, Elsevier Science Direct, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and in reference lists of articles and systematic reviews. Score of the International Index of Erectile Function (IIEF) was used as the outcome measurement, and standardized mean differences (SMD) with 95% CI were calculated. Results. Eleven studies were included, including 535 men with AS and 430 male controls. Each domain of the IIEF score (erectile function: SMD −0.52, 95% CI −0.68 – −0.37; orgasmic function: −0.72, −1.03 – −0.42; sexual drive: −0.40, −0.62 – −0.18; intercourse satisfaction: −0.86, −1.15 – −0.56; and overall satisfaction: −0.61, −0.91 – −0.32) were lower in men with AS than in controls. In the subgroup analysis, the results did not change except for the sexual drive in the Asians group (−0.15, −0.42–0.13). At metaregression, no study characteristics were significantly associated with effect size of the IIEF score. Conclusion. Sexual function is impaired in male patients with AS and further studies are necessary to better understand risk factors for sexual dysfunction in this population.

The relationship between DRD2 gene polymorphisms (C957T and C939T) and schizophrenia: A meta-analysis

Schizophrenia is a common, complex multi-factorial psychiatric disorder. Many studies have reported associations between the C957T and C939T polymorphisms in Dopamine D2 receptor (DRD2) gene and schizophrenia, but results are inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was conducted to systematically summarize the possibility. We included 13 articles involving 3079 schizophrenia cases and 3851 healthy controls. Positive associations were found between C957T polymorphism and schizophrenia risk in C vs. T (OR=1.26, 95% CI=1.09-1.46, Praw=0.002, PFDR=0.005) and CC+CT vs. TT (OR=1.47, 95% CI=1.25-1.73, Praw<0.001, PFDR<0.001). When stratified by race, a significantly increased risk of schizophrenia was observed in Caucasians, but not in Asians. No association between C939T polymorphism and schizophrenia was found in overall or Asian population. Our study suggested that C957T of DRD2 gene polymorphism is likely to be a risk factor for schizophrenia, especially in Caucasian.

Association between circulating adipokines, radiographic changes, and knee cartilage volume in patients with knee osteoarthritis.

Objectives: To explore the associations between serum adipokine levels, radiographic osteoarthritis (ROA) severity, and articular cartilage volume in patients with knee OA. Method: A cross-sectional sample of 205 patients (aged 45–74 years) with knee OA were consecutively recruited to the Anhui Osteoarthritis (AHOA) study. ROA was assessed using the Kellgren–Lawrence (KL) grading system (grades 0–4). Knee cartilage volume was determined using fat-saturated T1-weighted magnetic resonance imaging (MRI). Serum levels of the adipokines leptin, adiponectin, and resistin were measured by using an enzyme-linked immunosorbent assay (ELISA). Results: Serum adiponectin, but not serum leptin or resitin, was significantly associated with reduced ROA severity in univariable analyses and this association remained significant after adjustment for age, sex, body masss index (BMI), and disease duration [β = −0.012, 95% confidence interval (CI) −0.021 to −0.002]. In ROA patients, leptin was significantly and positively associated with knee cartilage volume at patellar and medial tibial sites in both unadjusted and adjusted analyses (β = 0.006, 95% CI 0.02–0.010 for medial tibia and β = 0.009, 95% CI 0.001–0.018 for patella sites) but adiponectin and resistin had no significant associations with cartilage volume. In non-ROA patients, leptin, adiponectin, and resistin were not significantly associated with cartilage volume at any site. Conclusions: Serum levels of leptin are independently associated with increased knee cartilage volume. In addition, serum adiponectin is significantly and negatively associated with ROA severity, suggesting a potentially protective effect.

Association of IL-1F7 gene with susceptibility to human leukocyte antigen-B27 positive Ankylosing spondylitis in Han Chinese population

Ankylosing spondylitis (AS) is one of the most common inflammatory arthritis, with an estimated prevalence of 0.1%–0.9%. Genetic factors have been strongly implicated in its etiology. Assessed by twin studies, the heritability of AS has been estimated to be 90% [1]. The disease has a strong genetic association with human leukocyte antigen-B27, however, only 1%–5% among those HLA-B27 positive populations developed AS, although most AS patients are HLA-B27 positive. Apparently, HLA-B27 alone does not account for the pattern of AS recurrence. Indeed, the contribution of HLA-B27 to the overall genetic predisposition has been estimated to be only 20%–30%. It has been proposed that non-major histocompatibility complex (non-MHC) genes contribute a major portion of genetic susceptibility to AS [2]. Genome-wide scans have demonstrated several areas of suggestive or significant linkage in non-MHC regions, including 1p, 1q, 2p, 3p, 2q, 5q, 9q, 10q, 11p, 11q, 16q, 17p, 17q and 19q [1,3,4]. Yet, candidate gene studies for non-MHC are limited. A genome-wide scan has identified that a region including interleukin-1 (IL-1) family gene cluster, which lies 123–126 cM from the p-telomere of chromosome 2, is linked to AS susceptibility [4]. Within a 360-kb region, IL-1 gene cluster includes IL-1α (IL1A), IL-1β (IL1B), IL-1F7, IL-1F9, IL-1F6, IL-1F8, IL-1F5, IL-1F10 and IL-1RN genes. This linkage finding was later confirmed by family-based association studies in western Canadian families population [5,6]. Based on these findings, Timms et al. concluded that the IL-1 gene cluster contains a susceptibility locus for AS [7]. Currently studies largely focus on IL-1A/B and IL-1RN genes [8,9]. It is noted that, across different populations, the association between AS and the polymorphisms of IL-1 gene is not identical, although similar [10,11]. Also, information regarding the association between IL-1 polymorphisms and AS is very limited in Chinese population. Therefore, we performed a case–control study on the association between AS and IL-1F7 gene single-marker polymorphism in concert with HLAB27 in Chinese population. We studied 181 unrelated AS patients (111 males and 70 females) with mean age of 26.3 y (SD=6.4 y), and 158 controls individuals (102 males and 56 females) with mean age of 28.2 y (SD=7.4 y). All the cases and controls are HLA-B27 positive. To reduce the influence of population stratification farthest, all the samples in our study are from local Anhuilanders, whose parents are also Anhuilanders. Permission was obtained from all individuals who were enrolled in this study. All patients were recruited from Department of Rheumatology, First Affiliated hospital, Anhui Medical University. All those control individuals had been screened by experienced rheumatism doctors before their blood samples were collected. Clinical diagnosis was carried out strictly according to the modified New York criteria [14]. Two IL-1F7 SNPs were selected from NCBI dbSNP (dbSNP home page).

Association of FCRL4 polymorphisms on disease susceptibility and severity of ankylosing spondylitis in Chinese Han population

Previous studies have found that the Fc receptor-like (FCRL) molecule, involved in controlling B cell signaling, may contribute to the autoimmune disease process. Many studies have reported the relation of FCRL gene family with SLE and RA. We hypothesized that FCRL4 may be a key gene for ankylosing spondylitis (AS) development. To test this hypothesis, we screened FCRL4 polymorphisms in the Chinese Han population. Five tag single nucleotide polymorphisms (SNPs), including rs14335, rs849826, rs10489674, rs2778003, and rs2777963, were selected. Using a case–control study, five tag SNPs, which captured the majority of known common variation within FCRL4 gene, were selected and genotyped by Multiplex Snapshot technique. We analyzed 299 patients and 300 controls from China. The genotype analysis demonstrated that one of the FCRL4 tag SNPs rs2777963 TT genotype may be a risk factor of AS (χ2 = 7.374, p = 0.024). The haplotype analysis indicated that there were no significant differences between AS cases and controls. Patients with AS who had rs14335 AA genotype had a significantly declined visual analogue scale patients global assessment scores compared to those with the GG genotype (31.21 ± 26.25 vs 40.54 ± 25.40, p = 0.035) and GA genotype (38.29 ± 24.94 vs 40.54 ± 25.40, p = 0.044), and in locus rs10489674, TT genotype had significantly increased Bath Ankylosing Spondylitis Disease Activity Index scores compared to those with the CC genotype (4.73 ± 2.43 vs 3.15 ± 1.61, p = 0.003) and CT genotype (4.73 ± 2.43 vs 2.97 ± 1.71, p = 0.001). The FCRL4 polymorphisms may play an important role in the susceptibility and severity of AS in the Chinese Han population.

Treatment with Etanercept in a Patient with Rheumatoid Arthritis-Associated Interstitial Lung Disease

We report a case of a 52-year-old woman with a 1-year history of rheumatoid arthritis-associated interstitial lung disease referred to hospital because of aggravated pulmonary symptoms in spite of intensive treatment including prednisone, azathioprine and triptergium glycoside. We subsequently initiated treatment with 25 mg of etanercept, subcutaneously injected twice weekly. Following 6 months of therapy with this agent, sustained improvement in dyspnea, cough was reported by the patient and respiratory function test showed marked improvement. The improvement was confirmed by reduced middle and lower lung markings on chest radiography and high-resolution CT scan. This report suggests etanercept may be effective in the treatment of rheumatoid arthritis-associated interstitial lung disease.