Molecular analysis of HLA-D region genes in seropositive rheumatoid arthritis

Analysis of HLA DRB1 and DQB1 Bam HI RFLPs revealed four DRB1 (4.8, 5.2, 6.0 and 7.0 kb) fragments and a 3.2 kb DQB1 fragment to be significantly increased in Caucasians with seropositive RA compared to healthy individuals. The 4.8, 5.2 and 7.0 kb DRB1 fragments were found in 86.5% of RA patients and in 56% of the controls (p = 10(-3), relative risk (RR) = 5.0), while the 6.0 kb fragment was found in 79% of RA patients compared to 32% of controls (p = 2 x 10(-5), RR = 8.0). The 3.2 kb DQB1 fragment was observed in 63.5% of RA patients versus 38.0% of controls (p = 10(-2), RR = 2.8). Analysis of these fragments relative to HLA phenotypes revealed that the 4.8, 5.2 and 7.0 kb DRB1 fragments were strongly correlated with DR4, -7, -9 and -w53 serotypes, the 6.0 kb RFLP with DR4 and the 3.2 kb DQB1 fragment with DR1 and DQw1. Using probes specific for the 5' or 3' regions of the DRB1 gene, the 5.2 and 6.0 kb DRB RFLPs were mapped to the 5' end and the 4.8 and 7.0 kb RFLPs to the 3' end of the DRB1 gene. A probe generated from the second exon of the DRB4 (DRw53) gene recognized only the 5.2 and the 6.0 kb RFLPs corroborating the 5' location of these RFLPs. Family studies further confirmed that these RFLP's segregated with HLA phenotypes.     

Aberrant T-regulation in rheumatoid arthritis and IgA nephropathy affects CD5+ and CD5- B lymphocytes equally.

T-suppressor function and T-helper function in healthy adults, elderly patients with non-immune diseases, and patients with rheumatoid arthritis (RA) and IgA nephropathy (IgAN) were titrated by adding graded concentrations of CD8+ cells to autologous CD8-depleted peripheral blood mononuclear cells (PBMC), or CD4+ cells to CD8- 4- PBMC, respectively. Following culture with pokeweed mitogen (PWM), numbers of CD5+ and CD5- immunoglobulin-secreting cells were determined using a combination of rosetting with anti-CD5-coated Dynabeads and reverse haemolytic plaque formation (Jones, 1990). Of 11 RA patients studied, eight had slightly reduced suppressor activity for CD5+ and CD5- IgM-secreting cells, and three with active disease and high serum levels of C-reactive protein, could not suppress IgG, IgA or IgM secretion by either B subset. Helper activity for both CD5+ and CD5- B cells was slightly but significantly increased in RA patients. One of eight patients with IgAN could not suppress IgG, IgA or IgM production by CD5+ or CD5- B cells, and all IgAN patients required strikingly fewer CD4+ cells for PWM-induced activation of CD5+ and CD5- B cells than controls. It was concluded that in two immunologically mediated diseases in which some patients have raised numbers of circulating CD5+ B cells, aberrant T-regulation affects CD5+ and conventional CD5- B cells equally.     

Impaired late suppression of Epstein-Barr virus (EBV)-induced immunoglobulin synthesis: A common feature of autoimmune disease

We examined regulation of Epstein-Barr virus-induced plaque-forming cell generation in peripheral blood mononuclear cells from several autoimmune and seronegative diseases and correlated these results with Epstein-Barr virus-induced proliferation. We confirmed the defective regulation of Epstein-Barr virus-induced plaque-forming cells in peripheral blood mononuclear cells of patients with rheumatoid arthritis and scleroderma. Peripheral blood mononuclear cells from patients with seronegative arthropathies and chronic infective inflammation (cystic fibrosis) had normal regulation of Epstein-Barr virus-induced plaque-forming cells. Peripheral blood mononuclear cells from rheumatoid arthritis had excessive plaque-forming cell generation in the face of a normally regulated decrease in Epstein-Barr virus-induced proliferation. In contrast, peripheral blood mononuclear cells from scleroderma had defective suppression of both Epstein-Barr virus-induced proliferation and plaque-forming cell generation. Thus, impaired regulation of Epstein-Barr virus-induced plaque-forming cell generation is a common feature of autoimmune disease and demonstrates some specificity for these disorders.     

Polymorphisms of toll-like receptor 2 and 4 genes in rheumatoid arthritis and systemic lupus erythematosus

Human toll-like receptors (TLRs) participate in the innate response and signal the activation of adaptive immunity. Therefore, these TLRs may be important in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We investigated, by using a polymerase chain reaction restriction-fragment length polymorphism method, the possible association between the polymorphisms of TLR2 (Arg677Trp and Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) genes with the susceptibility or severity of RA and SLE. Our study population consisted of 122 patients with SLE, 224 patients with RA, and a control group of 199 healthy individuals. The TLR2 polymorphisms were very rare in our population; no individual carrying the TLR2-Arg677Trp polymorphism was observed, whereas the TLR2-Arg753Gln polymorphism was present in only 1% of the total population. We found no statistically significant differences in the TLR4-Asp299Gly and the TLR4-Thr399Ile genotype or allele distribution between SLE patients, RA patients, and control individuals. Similarly, no association was found with any of the demographic and clinical parameters tested either in RA or in SLE patients. In conclusion, a case-control study was used to analyze, for the first time, the influence of TLR2 and TLR4 gene polymorphism on the predisposition and clinical characteristics of SLE and RA but provided no evidence for association of TLR2 or TLR4 gene polymorphism with either disease in the population under study.     

Rheumatoid arthritis may be primarily associated with HLA-DR4 molecules sharing a particular sequence at residues 67–74

Genomic typing of in vitro amplified DNA with sequence-specific oligonucleotide (SSO) probes was performed for DRB1, DQA1, DQB1, DPA1 and DPB1 alleles in 54 random Norwegian rheumatoid arthritis (RA) patients and 181 healthy controls. DRB1 alleles encoding the serological specificity DR4 were found in 80% of the patients, compared to 34% of the controls (relative risk = 7.9, p less than 0.0001). All DR4-positive RA patients carried either DRB1*0401 (Dw4), 0404 (Dw14), or 0405 (Dw15), while no patients were found to carry DRB1*0402 (Dw10) or 0403 (Dw13). The frequency of the DRB1*0101 allele encoding DR1 was not increased, even among DR4-negative RA patients, and we were unable to detect any sharing of other class II alleles among DR4-negative patients. No contribution of any DQA1, DQB1, DPA1 or DPB1 alleles to RA susceptibility could be detected. The results suggest that in the Norwegian population RA is primarily associated with a shared sequence at residues 67-74 of the DR beta 1 chain, but only when this sequence is expressed on DR4 molecules.     

Plasma protein binding of imipramine in patients with rheumatoid arthritis

Summary In 23 patients with rheumatoid arthritis the plasma protein binding of³H-imipramine and the plasma levels of 13 proteins were measured in order to examine the significance of the proteins for the binding of imipramine. The degree of³H-imipramine binding did not differ significantly from that in healthy controls. It was positively correlated with the concentrations of fibrinogen, ₁-acid-glycoprotein, ceruloplasmin, complement C3_c, haptoglobin and hemopexin. Erythrocyte sedimentation rate was also highly positively correlated with binding. The concentration of several of the proteins showed a significant covariation. The³H-imipramine binding was negatively correlated with the concentration of albumin and the latter was negatively correlated with some of the proteins mentioned-above. No correlation with the levels of apolipoproteins A and B was found. There appears to be more a qualitative than a quantitative change in³H-imipramine binding in patients with rheumatoid arthritis.     

铁死亡相关肌肉骨骼系统疾病的概述及中医药干预进展

铁死亡是一种新型的细胞死亡形式,与铁过载和脂质过氧化有关,在许多疾病的发展中具有重要作用。骨质疏松症、骨关节炎、类风湿关节炎、骨肉瘤、脊髓损伤、肌少症等肌肉骨骼系统疾病严重影响患者生活质量,已成为全球公共卫生系统的主要负担。铁死亡与上述肌肉骨骼系统疾病的发生发展密切相关,表明铁死亡可能成为肌肉骨骼系统疾病的治疗的新靶点。中医药在肌肉骨骼系统疾病治疗中有其独特的优势,已有大量研究证实中医药通过铁死亡途径参与肌肉骨骼系统疾病的调节,显示出良好的研究前景。通过探讨铁死亡与肌肉骨骼系统疾病的关联,总结中医药通过介导铁死亡防治肌肉骨骼系统疾病研究进展,为开发新的治疗策略及中医药更好的治疗肌肉骨骼系统疾病治疗提供思路。     

Mental Health of Mothers of Children with Juvenile Rheumatoid Arthritis: Appraisal as a Mediator

Examined direct and mediated relations between condition parametersand maternal mental health for 53 mothers of 2- to 11-year-oldchildren with juvenile rheumatoid arthritis (JRA). Multivariateanalyses revealed that when considered simultaneously, indicesof both biological severity and functional severity were associatedsignificantly with maternal mental health. Further, mother'sappraisals of the impact of the child's illness on the familypartially mediated the effects of medication type and child'sfunctional status on mother's mental health. Results providesupport for conceptual models that emphasize the cognitive mechanismsby which condition parameters such as biological and functionalseverity might affect maternal mental health. Explicating theprocesses by which a child's JRA might lead to psychologicaladjustment problems in the parent has implications for developingpreventive and treatment interventions.     

HLA—DR4基因与类风湿关节炎的关联性研究

目的探讨人类白细胞抗原HLA-DR4基因与类风湿关节炎(RA)的关联性.方法采用特异性引物聚合酶链反应(PCR-SSP)方法对山东地区汉族人群132例类风湿关节炎患者及130例正常健康者的HLA-DR4基因进行分析,并测定其基因频率.结果 HLA-DR4基因在132例类风湿关节炎患者中的基因频率(46.2%)显著高于其在130例正常对照组中的基因频率(19.2%,x2=21.624,P＜0.01).结论 HLA-DR4基因与山东地区人群的类风湿关节炎易感性有关联.