The relationship between serum zinc levels and rheumatoid arthritis activity

Objective

Rheumatoid arthritis (RA) is one of the most prevalent chronic autoimmune diseases; it typically involves the hands, wrists, ankles, and eventually all joints. Some studies have reported that zinc serum levels are lower in patients with RA than in healthy individuals.

Materials and Methods

Seventy-nine patients with RAwere selected. The patients were all less than 75 years old and were diagnosed by a rheumatologist. Serum zinc levels were measured using the flame photometry method with a blood sample of 5 mL. The relationship between the average serum zinc level and disease activity was analyzed based on the DAS28 scoring scale for different RA groups. The significance threshold was set at p<0.05. Data analyses were implemented in SPSS 22.0.

Results

There was a significant inverse relationship between the serum zinc levels and disease activity. Chi-square tests were used to compare zinc serum levels with respect to disease activity. There were significant differences in zinc levels among three groups of patients with different levels of disease severity, such that disease activity increased as the serum zinc level decreased (p<0.001).

Conclusion

There was a significant inverse relationship between the serum zinc level and RA activity based on the DAS28 score. Therefore, it is recommended that mineral deficiencies should be addressed by optimizing the zinc supply along with other standard medications in order to reduce RA activity.

     

Possible case of rheumatoid arthritis from Sudanese Nubia

Due to its apparent absence in archaeologically derived skeletons, rheumatoid arthritis (RA) has generally been believed to be of fairly recent origin. A growing body of evidence now demonstrates that erosive lesions typical of RA are present in archaeological populations and that the antiquity of RA may be greater than previously expected. In support of this argument, a case of erosive arthritis is reported in a skeleton from Kulubnarti, Republic of the Sudan (c. 700-1450 A.D.). Lytic, erosive lesions and subchondral cysts are present bilaterally in the carpal and metacarpal joints of a female skeleton with an estimated age at death of 50+ years. These lesions are typical of those seen in clinically diagnosed rheumatoid patients. While their expression and distribution are highly suggestive of RA, interpretation must be made with due consideration for problems of differential diagnosis of this disease in archaeological material.     

人体菌群与类风湿性关节炎相关性的研究进展

类风湿性关节炎(rheumatoid arthritis,RA)是一种慢性炎症性自身免疫性疾病,严重影响患者生理以及心理健康。尽管过去20多年RA的治疗进展迅速,但我们对RA的病因学仍知之甚少。研究表明,RA的发病与遗传、环境以及免疫这三大因素息息相关。众所周知,人体菌群与这三大因素亦有着密切的联系。越来越多的临床试验及动物实验指出,人体菌群失调在RA病程的发生发展中起着至关重要的作用。本综述整理近年来人体菌群与类风湿性关节炎相关性的研究进展,通过循证人体菌群,为类风湿性关节炎的诊断、预防和治疗提供新思路。     

The relationship between cancer and rheumatoid arthritis: still a large research agenda

The association between rheumatoid arthritis (RA) and malignancies has received increased attention in recent years. Reports suggesting that tumor necrosis factor blockers might elevate the risk of malignancy in RA patients have prompted researchers to look at the incidence of malignancies in all RA patients. In a recent issue of Arthritis Research & Therapy, Smitten and colleagues suggest that previous reports of a standardized incidence ratio close to one for malignancies in RA may reflect an increased risk for some site-specific malignancies and a reduced risk for others. Here we discuss these findings and suggest what issues could be addressed in future studies.     

Associations between marginal periodontitis and rheumatoid arthritis

Chronic destructive periodontitis is no longer considered to be just a local inflammatory process afflicting the periodontal tissues, but a systemic infection. Bacteria, their products and various pro-inflammatory cells and substances can penetrate into the blood stream and infect distant organs and structures. Periodontitis and rheumatoid arthritis indicate several common histo-pathological correlations, as the destroyed osseous tissues and cartilages are permanently washed with inflammatory fluid full of proteolytic and osteolytic substances. Although exact causal and molecular associations between both diseases have not been explained yet, there are some common etiopathogenic correlations that can have influence on relationship between both diseases. Among these factors belong: a positive finding of common genes, genetic polymorphisms and hyper-inflammatory types of some immune competent cells and molecules, common cytokine profiles and increased concentrations of pro-inflammatory mediators in periodontal and joint structures. Periodontitis and some periodontal pathogens can influence various auto-immune reactions connected with rheumatoid arthritis (RF, anti-CCP). Possible causal associations are indicated in some studies dealing with treatment of RA, when a beneficiary effect of RA treatment led to improvement of some periodontal parameters. This relationship works both ways; the periodontal therapy had positive influence on some markers of rheumatoid arthritis. This provides sufficient theoretic evidence to perform professional and personal oral hygiene in a more active way.     

Altered expression and glycosylation of plasma proteins in rheumatoid arthritis

Altered glycosylation of plasma proteins has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). The present study investigated the changes in the Concanavalin-A (Con-A)-bound plasma proteins in the RA patients in comparison to that of the healthy controls. Two proteins (MW ∼32 kDa and ∼62 kDa) showed an alteration in expression while an altered monosaccharide profile (high mannose) was observed in the ∼62 kDa protein in the samples collected from RA patients. The 2-dimensional polyacrylamide gel electrophoresis analysis of the Con-A-bound plasma samples showed a large number of protein spots, a few of which were differentially expressed in the RA patients. Some unidentified proteins were detected in the RA patients which were absent in the control samples. The present study, therefore, enunciates the role of carbohydrates as well as that of the acute phase response in the disease pathogenesis.     

HLA-linked rheumatoid arthritis.

Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the susceptibility allele frequency as 2.16%, and estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-half of familial RA, although it accounts for only approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically.     

Fungal arthritis simulating juvenile rheumatoid arthritis.

Petriellidium boydii is often isolated from maduromycosis but has recently been associated with arthritis. A previously healthy 6-year-old boy developed chronic purulent arthritis of the knee after a bicycle accident. Culture of aspirate grew no pathogens and antibiotic treatment had no effect. Culture of synovial fluid grew P boydii, which responded initially to amphotericin but reappeared after six months. Subsequent treatment with miconazole was stopped after development of haematuria. The fungus was sensitive to ketoconazole, and treatment with this drug cured the infection. With the introduction of ketoconazole it is of practical importance to recognise fungal infections.     

The association between rheumatoid arthritis and periodontal disease

Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. Nevertheless, many mechanisms in the pathogenesis have not yet been examined sufficiently, so that a final explanatory model is still under discussion, and we hereby present arguments in favor of this. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that support the hypothesis that oral infections play a role in RA pathogenesis. Of special importance are the impact of periodontal pathogens, such as Porphyromonas gingivalis on citrullination, and the association of PD in RA patients with seropositivity toward rheumatoid factor and the anti-cyclic citrullinated peptide antibody.     

Comparison between penicillamine and sulphasalazine in rheumatoid arthritis: Leeds-Birmingham trial.

Sulphasalazine was first formulated by Svartz in the early 1940s, specifically for use as a remission inducing drug in rheumatoid arthritis. After the publication of an unfavourable trial, however, the drug was restricted to patients with ulcerative colitis. In the late 1970s sulphasalazine was re-examined in rheumatoid arthritis and favourable results reported in "open" trials. A double blind controlled trial was therefore conducted comparing enteric coated sulphasalazine and D-penicillamine in patients with active rheumatoid arthritis. A total of 63 patients were recruited in two centres; 31 were treated with sulphasalazine and 32 received penicillamine. After 16 weeks'' treatment both drugs had produced significant improvements in clinical score, pain score measured on a visual analogue scale, grip strength, Ritchie articular index, erythrocyte sedimentation rate, and serum C reactive protein concentration. Nausea was the major side effect in the sulphasalazine treated group. No potentially dangerous effects of sulphasalazine were encountered in contrast with those seen in the penicillamine group. The results suggest that sulphasalazine is an effective and safe drug capable of producing remissions in active rheumatoid arthritis. They also lend confidence to the use of preliminary "open" trials as a means of screening for remission inducing drugs in rheumatoid arthritis.     

Association of MHC and rheumatoid arthritis. HLA polymorphisms in phenotypic variants of rheumatoid arthritis

Genes in the human leukocyte antigen (HLA) region remain the most powerful disease risk genes in rheumatoid arthritis (RA). Several allelic variants of HLA-DRB1 genes have been associated with RA, supporting a role for T-cell receptor-HLA-antigen interactions in the pathologic process. Disease-associated HLA-DRB1 alleles are similar but not identical and certain allelic variants are preferentially enriched in patient populations with defined clinical characteristics. Also, a gene dosing effect of HLA-DRB1 alleles has been suggested by the accumulation of patients with two RA-associated alleles, especially in patient subsets with a severe disease course. Therefore, polymorphisms in HLA genes are being explored as tools to dissect the clinical heterogeneity of the rheumatoid syndrome. Besides HLA polymorphisms, other risk genes will be helpful in defining genotypic profiles correlating with disease phenotypes. One such phenotype is the type of synovial lesion generated by the patient. HLA genes in conjunction with other genetic determinants may predispose patients to a certain pathway of synovial inflammation. Also, patients may or may not develop extraarticular manifestations, which are critical in determining morbidity and mortality. HLA genes, complemented by other RA risk genes, are likely involved in shaping the T-cell repertoire, including the emergence of an unusual T-cell population characterized by the potential of vascular injury, such as seen in extraarticular RA.