Polymyositis (PM) is an idiopathic inflammatory myopathy that affects striated muscles. Dermatomyositis (DM) is an idiopathic inflammatory myopathy with presence of skin symptoms. Both are characterized by acute or subacute onset, symmetrical proximal muscle weakness, the presence of mononuclear cell infiltrates of the muscles and increased activity of muscle enzymes. The treatment still remains glucocorticoids and disease-modifying drugs. Symptoms of PM/DM can be a signal of developing cancer. Known risk factors for cancer in patients with PM/DM are older age, male gender, dysphagia, skin necrosis, cutaneous vasculitis, rapid onset of the disease, elevated creatinine kinase (CK) and C reactive protein (CRP), and an increase in the erythrocyte sedimentation rate (ESR). Recently three new myositis-specific autoantibodies (MSA) predicting the risk of cancer have been discovered: melanoma differentiation-associated protein 5 (anti-MDA-5), transcription intermediary factor 1γ (TIF-1γ), and nuclear matrix protein NXP-2.

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ObjectivesEnhanced/disturbed activities of monocytes are crucial for perpetuation and for development of rheumatoid arthritis (RA). Therefore, knowledge about monocyte activities and regulation of molecular pathways operating within monocytes early in the course of RA development may help to predict the progression to the full-blown disease. We aimed to investigate the profile of miRNAs expression in circulating monocytes and monocyte-related cytokines in sera of individuals at undifferentiated arthritis (UA) stage, wich could serve as new biomarkers for RA development.Material and methodsMagnetically sorted monocytes from peripheral blood of 20 UA patients served for total RNA isolation. RNA samples were used for microRNA profiling. Concentrations of CCL3/MIP-1α, M-CSF, CCL2/MCP-1, IL-6, TNF-α and IL-15 in sera of UA patients were measured using ELISA assays. Verification of diagnosis after 4 years of follow-up led to the identification of patients who developed RA (UA→RA patients) and patients who remained still in UA phase (UA → UA patients). Comparisons between patients groups were performed using two-tailed Mann-Whitney U test.ResultsWe identified 50 miRNAs in monocytes with the largest variation of expression across all patients samples. From these selected miRNAs, expression of miR-642b-5p, miR-483-3p, miR-371b-5p were significantly up-regulated and miR-25-3p and miR-378d were significantly down-regulated in UA → RA vs. UA → UA patients. This specific pattern of miRNAs expression in circulating monocytes paralleled elevated IL-15 and M-CSF concentrations in sera of UA patients who progressed to RA.ConclusionsResults of our pilot study indicate that altered activity of monocytes can be detected at early stages of RA. We found new miRNA candidates differentially expressed in peripheral blood monocytes and elevated concentrations of IL-15 and M-CSF involved in monocyte activity and differentiation in patients with UA who subsequently developed RA, in comparison to UA patients who did not progress to RA after 4 years follow-up.

The distinguishing of the IgG4-related disease (IgG4-RD) from among other rheumatic diseases has brought attention to the IgG4 subclass of immunoglobulins. It is the least numerous subclass among immunoglobulins G. In general, IgG4 is considered to be non-inflammatory and tolerance inducing, due to its unique structure. However, in IgG4-RD this antibody plays a pathogenic role in activation of the fibrinogenesis and of the inflammatory process; there are also suggestions that it may be a marker of an abnormal inflammatory response. The importance of IgG4 for the pathogenesis of allergic diseases, with a vital role of its ratio to immunoglobulin E (IgE/IgG4 ratio), has been known for years. The role of IgG4 in the course and pathogenesis of rheumatic diseases is still being researched and is not yet fully understood. Increased IgG4 levels have been revealed in rheumatoid arthritis, although no clear link between this phenomenon and disease activity has been demonstrated. There are articles on the potential importance of IgG4 concentration (of both elevated and decreased serum levels) in Sjogren’s syndrome. Additionally, anti-nuclear IgG4 antibody significant titers have been detected in SLE patients, and it has been suggested that the effect of these antibodies on complement consumption and the production of proinflammatory cytokines may play a role in inhibiting the progression of SLE. IgG4 plays a role in autoimmune diseases other than rheumatic diseases, such as pemphigus, bullous pemphigoid, idiopathic membranous glomerulonephritis, or myasthenia gravis, but also in helmints infections. Research shows the importance of IgG4 in malignancy of neoplasms. Melanoma cells are known to stimulate IgG4 production through a modified Th2-based inflammatory response. The role of this immunoglobulin in cholangiocarcinoma is also considered as possible. The aim of this review article is to discuss the current knowledge of IgG4 not only from the perspective of the IgG4-RD but also from a point of view of other autoimmune diseases with particular emphasis on rheumatic diseases.

There is a need for definite diagnosis of rheumatoid arthritis (RA) at its earliest stages of development in order to introduce early and effective treatment. Here we assessed whether serum interleukin-15 (IL-15) can serve as a new biomarker of RA development in patients with undifferentiated arthritis (UA). Interleukin-15, IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) were measured in UA patients at inclusion. Six months later, the diagnosis was re-evaluated, and statistical analysis was performed. We found that at the UA stage, IL-15 was more prevalent in patients who progressed to RA than RF or anti-CCP Abs (83.3% vs. 61.1% and 66.7%, respectively). Interleukin-15 showed higher sensitivity (77.8%) than both autoantibodies and higher specificity (80.9%) than anti-CCP Abs in identification of UA patients who developed RA. The diagnostic utility of IL-15 was comparable to that of RF (AUC: 0.814 vs. 0.750, p > 0.05), but higher than that of anti-CCP Abs (AUC: 0.814 vs. 0.684, p = 0.04). The combined use of IL-15, RF and anti-CCP Abs yielded higher diagnostic accuracy for RA than autoantibodies determination only. Our results indicate that IL-15 can be used as a biomarker of RA development in patients with UA.