Autoantibodies and interstitial lung disease in rheumatoid arthritis: towards a 'mix-and-match' approach?

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Antioxidant and Ex Vivo Immune System Regulatory Properties of Boswellia serrata Extracts

Boswellia serrata (BS) is an important traditional medicinal plant that currently represents an interesting topic for pharmaceutical research since it possesses several pharmacological properties (e.g., anti-inflammatory, antimicrobial, and antitumour). The safety and versatility of this dietary supplement should allow for its use in numerous pathological conditions; however the quality of the extracts needs to be standardized to increase the clinical success rate resulting from its use. In the present study, different commercially available B. serrata extracts were employed to compare their AKBA content and in vitro antioxidant power. Furthermore, their ability to modulate the immune system regulatory properties was investigated. Our results showed that the AKBA content varied from 3.83 ± 0.10 to 0.03 ± 0.004%, with one sample in which it was not detectable. The highest antioxidant power and phenolic content were shown by the same extract, which also exhibited the highest AKBA concentration. Finally, the BS extracts showed the ability to influence the regulatory and effector T-cell compartments. Our results suggest that frankincense should be further investigated for its promising potentiality to modulate not only inflammation/oxidative stress but also immune dysregulation, but attention should be paid to the composition of the commercial extracts

Balance between Regulatory T and Th17 Cells in Systemic Lupus Erythematosus: The Old and the New

Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease. Treg cells appear to be impaired and therefore unable to counteract autoreactive T lymphocytes. Conversely, Th17 cells accumulate in target organs contributing to local IL-17 production and eventually tissue damage. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent an intriguing and useful tool for SLE treatment in the next future. In this paper, the current knowledge about Treg and Th17 cells interplay in SLE will be discussed

Altered Immunoregulation in Rheumatoid Arthritis: The Role of Regulatory T Cells and Proinflammatory Th17 Cells and Therapeutic Implications

In recent years several studies investigated the role of T lymphocyte subpopulations in the pathogenesis of rheumatoid arthritis (RA). Pathogenic Th17 cells mediate pannus growth, osteoclastogenesis, and synovial neoangiogenesis; hence they are key players in the development of the disease. On the other hand, regulatory T (Treg) cells are a T cell subset whose peculiar function is to suppress autoreactive lymphocytes. The imbalance between Th17 and Treg cells has been identified as a crucial event in the pathogenesis of RA. In addition, the effects of currently employed RA therapeutic strategies on these lymphocyte subpopulations have been extensively investigated. This review article aims to discuss current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder

Subclinical Atherosclerosis in Primary Sjögren's Syndrome: Does Inflammation Matter?

Sjögren's syndrome (SS) is a systemic autoimmune disease mainly characterized by inflammatory involvement of exocrine gland. Atherosclerosis is a complex process leading to plaque formation in arterial wall with subsequent cardiovascular (CV) events. Recently, numerous studies demonstrated that SS patients bear an increased CV risk. Since activation of immune system is a key element in atherosclerosis, it is interesting to analyze whether and how the autoimmune and inflammatory events characterizing SS pathogenesis directly or indirectly contribute to atherosclerosis risk in these patients. An increase in circulating endothelial microparticles and integrins, which may be a consequence of endothelial damage and impaired repair mechanisms, has been demonstrated in SS. Increased endothelial expression of adhesion molecules with subsequent infiltration of inflammatory cells into arterial wall is also a critical event in atherosclerosis. The early inflammatory events taking place in the atherosclerotic plaque cause an increase in alarmins, such as S100A8/A9, which seems to be associated with SS disease activity and, in turn, induce up-regulation of interleukin (IL)-1β and other pro-atherogenic cytokines. Interestingly, increased IL-1β levels were also detected in tertiary lymphoid structures developing in vessel adventitia adjacent to the atherosclerotic plaque, suggesting a direct role of IL-1β in this process. Similar to these structures, germinal center-like structures arising in SS exocrine glands are also tertiary lymphoid systems where T-helper (Th) cell subsets govern the adaptive immune response. Th1 cells are the most prevalent subtype and have been shown to be strongly involved in both SS pathogenesis and atherosclerosis. Th17 cells are attracting great interest and few studies showed its importance in SS development. Albeit in low amounts, a Th17 signature was also detected in atherosclerotic plaques and some animal models demonstrated a significant pro-atherogenic role and positive effects of IL-17A blockade. Despite the fact that T cells have a pivotal role in the inflammatory process that ultimately leads to atherosclerosis, B cells have also been detected in atherosclerotic plaques, although their exact role is still mostly unknown with studies showing contrasting results. In this scenario, the role of inflammation in atherosclerosis pathogenesis in patients with SS needs to be further explored

Targeting Inflammation to Prevent Cardiovascular Disease in Chronic Rheumatic Diseases: Myth or Reality?

Evidence for increased risk of cardiovascular morbidity and mortality in chronic inflammatory rheumatic diseases has accumulated during the last years. Traditional cardiovascular risk factors contribute in part to the excess of cardiovascular risk in these patients and several mechanisms, including precocious acceleration of subclinical atherosclerotic damage, inflammation, and immune system deregulation factors, have been demonstrated to strictly interplay in the induction and progression of atherosclerosis. In this setting, chronic inflammation is a cornerstone of rheumatic disease pathogenesis and exerts also a pivotal role in all stages of atherosclerotic damage. The strict link between inflammation and atherosclerosis suggests that cardiovascular risk may be reduced by rheumatic disease activity control. There are data to suggest that biologic therapies, in particular TNFα antagonists, may improve surrogate markers of cardiovascular disease and reduce CV adverse outcome. Thus, abrogation of inflammation is considered an important outcome for achieving not only control of rheumatic disease, but also reduction of cardiovascular risk. However, the actual effect of anti-rheumatic therapies on atherosclerosis progression and CV outcome in these patients is rather uncertain due to great literature inconsistency. In this paper, we will summarize some of the main mechanisms linking the inflammatory pathogenic background underlying rheumatic diseases and the vascular damage observed in these patients, with a particular emphasis on the pathways targeted by currently available therapies. Moreover, we will analyze current evidence on the potential atheroprotective effects of these treatments on cardiovascular outcome pointing out still unresolved questions

Multidisciplinary collaboration among young specialists: results of an international survey by the emerging EULAR network and other young organisations

Background: Multidisciplinary collaboration is defined as a collective work involving multiple disciplines and is common in clinical care and research. Our aim was to describe current clinical and research collaboration among young specialists and to identify unmet needs in this area. Methods: An online survey was disseminated by email and social media to members of the EMerging EUlar NETwork, the Young Nephrologists’ Platform, the Paediatric Rheumatology European Society Emerging Rheumatologists and Researchers and the European Academy of Allergy and Clinical Immunology Junior Members. Results: Of 303 respondents from 36 countries, 61% were female, 21% were aged below 30 years and 67% were aged 31–40 years. Young rheumatologists were the most represented (39%), followed by young nephrologists (24%), young paediatricians (20%), young allergologists (11%) then young internists (3%) and 3% other specialities. Collaborations were reported frequently by phone and email, also by various combined clinics while common local multidisciplinary meetings were uncommon. 96% would like to develop clinical research collaborations and 69% basic research collaborations. The majority of young specialists would be interested in online (84%) and/or 1–2 days (85%) common courses including case discussion (81%) and training workshops (85%), as well as webinars recorded with several specialists on a specific disease (96%). Conclusions: This collaborative initiative highlighted wishes from young specialists for developing (1) regular local multidisciplinary meetings to discuss complex patients, (2) clinical research collaboration with combined grants and (3) multidisciplinary online projects such as common courses, webinars and apps

Functional Improvement of Regulatory T Cells From Rheumatoid Arthritis Subjects Induced by Capsular Polysaccharide Glucuronoxylomannogalactan

Objective: Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal). Methods: Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells. Results: GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25-FOXP3+ Treg cells; ii) increase intracellular levels of TGF-beta1 in CD4+CD25-FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-gamma and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production. Conclusion: These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25-FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases