Arthritis diagnosis and symptoms are positively associated with specific physical job exposures in lower- and middle-income countries: cross-sectional results from the World Health Organization's Study on global AGEing and adult health (SAGE).

BACKGROUND: In higher income countries, work-related squatting and heavy lifting have been associated with increased arthritis risk. Here, we address the paucity of data regarding associations between arthritis and work-related physical stressors in lower- and middle-income countries. METHODS: Data were extracted from the Study on global AGEing and adult health (SAGE) Wave 1 (2007-10) for adults (aged ≥50 years) from Ghana, India, Russia and South Africa for whom detailed occupation data was available (n = 21,389; 49.2% women). Arthritis cases were identified using a symptom-defined algorithm (current) and self-reported doctor-diagnosis (lifetime). A sex-specific Job Exposure Matrix was used to classify work-related stressors: heavy physical work, kneeling/squatting, heavy lifting, arm elevation and awkward trunk posture. Using the International Standard Classification of Occupations, we linked SAGE and the Job Exposure Matrix. Logistic regression was used to investigate associations between arthritis and work-related stressors, adjusting for age (10 year age groupings), potential socioeconomic-related confounders, and body mass index. Excess exposure risk due to two-way interactions with other risk factors were explored. RESULTS: Doctor-diagnosed arthritis was associated with heavy physical work (adjusted odds ratios [OR] 1.12, 95%CI 1.01-1.23), awkward trunk posture (adjusted OR 1.23, 95%CI 1.12-1.36), kneeling or squatting (adjusted OR 1.25, 95%CI 1.12-1.38), and arm elevation (adjusted OR 1.66, 95%CI 1.37-2.00). Symptom-based arthritis was associated with kneeling or squatting (adjusted OR 1.27, 95%CI 1.08-1.50), heavy lifting (adjusted OR 1.33, 95%CI 1.11-1.58), and arm elevation (adjusted OR 2.16, 95%CI 1.63-2.86). Two-way interactions suggested excess arthritis risk existed for higher body mass index, and higher income or education. CONCLUSIONS: Minimization of occupational health risk factors is common practice in higher income countries: attention should now be directed toward reducing work-related arthritis burden in lower- and middle-income countries.

The association between rheumatoid arthritis and periodontitis.

The relationship between rheumatoid arthritis and poor oral health has been recognised for many decades. The association between periodontal infection and the risk of developing RA has been the subject of epidemiological, clinical and basic science research in recent times. Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis. The unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis and its contribution to the burden of citrullinated peptides is now well established. The impact of localized infection such as periodontitis in shaping specific anti-citrullinated peptide immune responses highlights a key area for treatment, prevention and risk assessment in rheumatoid arthritis.

Successes, challenges and developments in Australian rheumatology.

Australia is a geographically vast but sparsely populated country with many unique factors affecting the practice of rheumatology. With a population comprising minority Indigenous peoples, a historically European-origin majority population, and recent large-scale migration from Asia, the effect of ethnic diversity on the phenotype of rheumatic diseases such as systemic lupus erythematosus (SLE) is a constant of Australian rheumatology practice. Australia has a strong system of universal healthcare and subsidized access to medications, and clinical and research rheumatology are well developed, but inequitable access to specialist care in urban and regional centres, and the complex disconnected structure of the Australian healthcare system, can hinder the management of chronic diseases.

Fibroblasts and synovial immunity.

Rheumatoid arthritis (RA) synovium is characterised not only by increases in number and activity of lymphocytes and macrophages, but also of resident mesenchymal cells known as fibroblast-like synoviocytes (FLS). Originally thought of as passive structural cells, research over two decades has demonstrated the capacity for autonomous contributions of FLS to RA inflammation as effector cells producing cytokines and other pro-inflammatory mediators. More recently, as understanding of RA as a genuine autoimmune disease characterised by immunity to citrullinated proteins has grown, so the potential involvement of FLS in even proximal aspects of initiation and maintenance of abnormal adaptive immune responses has come to light. In this review we take a step-by-step approach to the role of FLS, considering their contribution to the phenomena, as currently understood, in RA pathogenesis. It can be concluded that significant evidence favours a broad role for FLS in synovial immunity, as well as inflammation.

Distinct in vivo roles of CD80 and CD86 in the effector T-cell responses inducing antigen-induced arthritis.

CD80 and CD86 play a critical role in the initiation of T-cell responses. However, their role in the in vivo effector CD4+ T-cell responses has been less extensively investigated. The current studies have examined the functional relevance of CD80 and CD86 in the effector CD4+ T-cell responses inducing antigen-induced arthritis. Arthritis was induced in C57BL/6 mice by sensitization to methylated bovine serum albumin (mBSA) on day 0, booster immunization (day 7) and intra-articular injection of mBSA (day 21). Control or anti-CD80 and/or anti-CD86 monoclonal antibodies were administered from day 21 to day 28. Arthritis severity and immune responses were assessed on day 28. The development of arthritis was significantly suppressed by inhibition of CD80 or CD86. Blockade of both CD80 and CD86 caused a trend towards reduced disease severity compared to control antibody-treated mice. Neutralization of CD80 attenuated accumulation of CD4+ T cells in joints and enhanced splenocyte production and circulating levels of interleukin-4. Inhibition of CD86 or both CD80 and CD86 reduced T-cell accumulation in joints without affecting T helper type 1/type 2 (Th1/Th2) differentiation or antibody levels. Blockade of CD86, and not CD80, significantly suppressed splenocyte interleukin-17 (IL-17) production. These results provide further in vivo evidence that CD80 and CD86 play important pathogenic roles in effector T-cell responses. CD80 exacerbates arthritis by downregulating systemic levels of IL-4 and increasing T-cell accumulation in joints without affecting IL-17 production. CD86 enhances disease severity by upregulating IL-17 production and increasing the accumulation of effector T cells in joints without affecting Th1/Th2 development.

Reduced leukocyte-endothelial cell interactions in the inflamed microcirculation of macrophage migration inhibitory factor-deficient mice.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with established roles in a range of inflammatory conditions. However, it is not known whether MIF influences inflammation via the direct promotion of leukocyte-endothelial cell interactions. Therefore, the aim of these experiments was to investigate the ability of MIF to regulate leukocyte-endothelial cell interactions in the inflamed microvasculature. METHODS: Intravital microscopy was used to examine postcapillary venules in the cremaster muscle and synovium of wild-type and MIF(-/-) mice. Leukocyte-endothelial cell interactions (rolling, adhesion, emigration) were compared under a range of inflammatory conditions. RESULTS: In cremasteric postcapillary venules of MIF(-/-) mice, lipopolysaccharide (LPS)-induced leukocyte rolling, adhesion, and emigration were significantly reduced relative to that in wild-type mice. Similar responses were observed in response to tumor necrosis factor alpha and histamine. Examination of the synovial microvasculature following exposure to carrageenan revealed that leukocyte rolling and adhesion in synovial postcapillary venules and leukocyte entry into the joint space were also reduced significantly in MIF(-/-) mice. In each of these models, the level of P-selectin-dependent rolling was reduced in MIF(-/-) mice. Despite this, no difference in P-selectin expression was observed following LPS treatment. However, microvascular shear forces were elevated in MIF(-/-) mice, raising a possible mechanism to explain the reduced interactions in these animals. CONCLUSION: MIF(-/-) mice consistently displayed a reduction in P-selectin-dependent rolling, suggesting that MIF exerts proinflammatory effects, in part, via the promotion of P-selectin-mediated rolling. Together, these data indicate that MIF promotes interactions between leukocytes and endothelial cells, thereby enhancing the entry of leukocytes into sites of inflammation.