Hyperferritinaemia: An Iron Sword of Autoimmunity

2019 ◽  
Vol 25 (27) ◽  
pp. 2909-2918 ◽  
Author(s):  
Joanna Giemza-Stokłosa ◽  
Md. Asiful Islam ◽  
Przemysław J. Kotyla

Background:: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Methods:: Different electronic databases were searched in a non-systematic way to find out the literature of interest. Results:: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still’s diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. Conclusion:: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

Immunology ◽  
2016 ◽  
Vol 148 (3) ◽  
pp. 237-248 ◽  
Author(s):  
Xiao-qin Wu ◽  
Yao Dai ◽  
Yang Yang ◽  
Cheng Huang ◽  
Xiao-ming Meng ◽  
...  

2002 ◽  
Vol 277 (31) ◽  
pp. 27903-27911 ◽  
Author(s):  
Vasudevan Seshadri ◽  
Paul L. Fox ◽  
Chinmay K. Mukhopadhyay

1983 ◽  
Vol 61 (9) ◽  
pp. 1032-1040 ◽  
Author(s):  
Sailen Mookerjea ◽  
Timothy Coolbear ◽  
Mohan Lal Sarkar

Studies on the developmental changes in oviducts of hormone-treated chicks and embryos of sea urchins have indicated that the level of dolichol phosphate in the tissues may serve as a control for asparagine-linked glycoprotein biosynthesis. Acute-phase reactant glycoprotein biosynthesis is greatly increased in inflamed rats given a single injection of turpentine. As most of the serum glycoproteins are synthesized via the dolichol pathway, the rate of synthesis of mannosyl and glucosyl dolichol monophosphate and of glucosyl dolichol pyrophosphoryl oligosaccharide, CTP-dependent doiichol phosphokinase, and the level of dolichol phosphate were measured in the livers of inflamed rats. The activities of the glycosyltransferases were increased at least twofold as a result of inflammation. It was also observed that dexamethasone treatment reversed the inflammation-induced increase of mannosyl and glucosyl transfer to dolichol monophosphate. The endogenous level of dolichol phosphate and dolichol kinase activity were increased in microsomes 24 h after inflammation. With exogenous dolichol added to the microsome assay, increased kinase activity was observed as early as 6 h after turpentine injection. The increase of dolichol phosphate in inflammation is most likely due to both greater availability of dolichol and an increase in the level of CTP-dependent dolichol kinase. Studies with purified subcellular fractions showed that dolichol kinase activity is primarily localized in the rough endoplasmic reticular fraction. Since this is the major site of dolichol-phosphate-linked N-glycosylation reactions, a key role of dolichol phosphokinase activity in rough microsomes to initiate the first steps of N-glycoprotein synthesis seems plausible.


2021 ◽  
Vol 2 ◽  
Author(s):  
Latifa Koussih ◽  
Samira Atoui ◽  
Omar Tliba ◽  
Abdelilah S. Gounni

Pentraxins are soluble pattern recognition receptors that play a major role in regulating innate immune responses. Through their interaction with complement components, Fcγ receptors, and different microbial moieties, Pentraxins cause an amplification of the inflammatory response. Pentraxin-3 is of particular interest since it was identified as a biomarker for several immune-pathological diseases. In allergic asthma, pentraxin-3 is produced by immune and structural cells and is up-regulated by pro-asthmatic cytokines such as TNFα and IL-1β. Strikingly, some recent experimental evidence demonstrated a protective role of pentraxin-3 in chronic airway inflammatory diseases such as allergic asthma. Indeed, reduced pentraxin-3 levels have been associated with neutrophilic inflammation, Th17 immune response, insensitivity to standard therapeutics and a severe form of the disease. In this review, we will summarize the current knowledge of the role of pentraxin-3 in innate immune response and discuss the protective role of pentraxin-3 in allergic asthma.


2014 ◽  
Vol 95 (1) ◽  
pp. 80-82
Author(s):  
G R Khaliullina ◽  
S L Blashkova

The review of clinical and immunologic studies of periodontal inflammatory diseases is presented. At present, the most effective tools for treatment of malocclusions are fixed orthodontic appliances (dental braces), but the use of fixed appliances complicates the oral hygiene, predisposes to periodontal and gum inflammation. The rate of complications diagnosed during orthodontic treatment stays high. The principles of periodontal inflammatory diseases (gingivitis, periodontitis) treatment are closely related with the causes and mechanisms of periodontal inflammation. Patients who receive orthodontic treatment using braces should be treated as a group with a high risk for inflammatory periodontal diseases. The orthodontic devices stimulate the directed reorganization of periodontal structures achieving optimal aesthetic and functional standards. Physiology of periodontium restructuring is largely determined by the local and general health before, during and after the orthodontic treatment. This article surveys the mechanisms of periodontal damage, highlighting the important role of immune response. So far, only anecdotal descriptions of immune response on the stages of orthodontic treatment are published.


2013 ◽  
pp. 40-46
Author(s):  
G.L. Bajocchi ◽  
N. Pipitone ◽  
P.L. Boiardi ◽  
C. Salvarani

BACKGROUND Interleukin-6 (IL-6) is a polyfunctional cytokine that regulates a very large number of cellular activities. Its implication in acute-phase reactant production by hepatocytes is of particular interest, as is its involvement in chronic inflammatory diseases, mainly rheumatoid arthritis, Crohn’s disease, and Castleman’s disease. Transgenic mice lacking IL-6 expression were completely protected against collagen-induced arthritis, and Tumor Necrosis Factor (TNF-alpha) induces synovial cells to produce IL-6 and their proliferation. However, there is still some controversies regarding the unique proinflammatory activity of IL-6. Some studies have demonstrated that IL-6 and TNF-alpha may have an opposite effect in synovial cultured cells since IL-6 could represent a negative loop for TNF-alpha induced synovitis. However, phase III studies of rheumatoid arthritis patients treated with anti IL-6 receptor (tocilizumab) indicate an acceptable safety profile relative to the clinical benefit. AIM OF THE STUDY In this review, we summarized the rationale and the main evidence regarding the therapeutic benefit of blocking IL-6 activity in rheumatoid arthritis.


2013 ◽  
Vol 154 (32) ◽  
pp. 1247-1255 ◽  
Author(s):  
Lajos Jakab

The acute and chronic constitutional reactions of the organism elicited by sterile causes and pathogenic structures threatening the soundness of the organism are surveyed by the author. It is emphasized that depending on causes which can be very different, there are various syndromes occurring in the clinical practice. On the basis of multitudiness of pathogenic factors and individual differences, the infammatory reactions are clinically, pathologically and pathobiochemically can be hugely variable. The acute inflammatory response may be sterile. It is often difficult to recognize in these processes whether the inflammation is harmful or beneficial for the organism as a whole. It is possible that the inflammatory response itself is the defending resource of the individual. The non-sterile acute inflammation is evoked by pathogenic microorganisms. The variety of clinical syndromes are explained by the high diversity of pathogenic microbes, the individualities of the defending organisms, and the natural and adaptive immunity of the organism which may be intact or possibly defective. In the latter case the inflammation itself is the disease, as a consequence of a pathological process conducted by the cortico-hypothalamo-adernal axis. The acute inflammation is a defending, preventing and repairing process, constituting an important part of the natural innate immune response. It is inseparable from the natural innate immune response, which is in close cooperation with the adaptive, specific immune response with mutual effects on each of the other. The conductor and the response reactions of the two immune responses are also the same. There are alterations in serum proteins/glycoproteins synthesized mostly by the hepatocytes. Because the concentration of almost all proteins/glycoproteins may change, the use of the discriminative term “acute phase reactant” is hardly relevant. For example, the HDL molecule is a negative “acute phase reactant”. On the gound of clinical, pathological and biochemical caracteristics, the chronic sterile inflammation is a very different entity. It has been established that atherosclerosis is one of the ab origine chronic inflammatory syndrome. It is a long-lasting pathological entity progressing, rather than resolving with different celerity, namely a unique vasculitis syndrome. We are speaking about risk factors instead of causes, which constitute larger or smaller groups to elicite the preventing reaction of the host. The propagations and final outcomes are quite different from that of the acute process. The disadvantages or benefits for the organism are scarcely predictable, albeit the chronic process may have roles in its prolonged nature. Orv. Hetil., 2013, 154, 1247–1255.


2021 ◽  
Vol 22 (8) ◽  
pp. 4283
Author(s):  
Christine Schlömmer ◽  
Anna Brandtner ◽  
Mirjam Bachler

Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin. However, AT levels drop in systemic inflammatory diseases. The reason for this decline is consumption by the coagulation system but also by immunological processes. Aside from the primarily known anticoagulant effects, AT elicits distinct anti-inflammatory signaling responses. It binds to structures of the glycocalyx (syndecan-4) and further modulates the inflammatory response of endothelial cells and leukocytes by interacting with surface receptors. Additionally, AT exerts direct antimicrobial effects: depending on AT glycosylation it can bind to and perforate bacterial cell walls. Peptide fragments derived from proteolytic degradation of AT exert antibacterial properties. Despite these promising characteristics, therapeutic supplementation in inflammatory conditions has not proven to be effective in randomized control trials. Nevertheless, new insights provided by subgroup analyses and retrospective trials suggest that a recommendation be made to identify the patient population that would benefit most from AT substitution. Recent experiment findings place the role of various AT isoforms in the spotlight. This review provides an overview of new insights into a supposedly well-known molecule.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sajjan Rajpoot ◽  
Kishore K. Wary ◽  
Rachel Ibbott ◽  
Dongfang Liu ◽  
Uzma Saqib ◽  
...  

The Toll-interleukin-1 Receptor (TIR) domain-containing adaptor protein (TIRAP) represents a key intracellular signalling molecule regulating diverse immune responses. Its capacity to function as an adaptor molecule has been widely investigated in relation to Toll-like Receptor (TLR)-mediated innate immune signalling. Since the discovery of TIRAP in 2001, initial studies were mainly focused on its role as an adaptor protein that couples Myeloid differentiation factor 88 (MyD88) with TLRs, to activate MyD88-dependent TLRs signalling. Subsequent studies delineated TIRAP’s role as a transducer of signalling events through its interaction with non-TLR signalling mediators. Indeed, the ability of TIRAP to interact with an array of intracellular signalling mediators suggests its central role in various immune responses. Therefore, continued studies that elucidate the molecular basis of various TIRAP-protein interactions and how they affect the signalling magnitude, should provide key information on the inflammatory disease mechanisms. This review summarizes the TIRAP recruitment to activated receptors and discusses the mechanism of interactions in relation to the signalling that precede acute and chronic inflammatory diseases. Furthermore, we highlighted the significance of TIRAP-TIR domain containing binding sites for several intracellular inflammatory signalling molecules. Collectively, we discuss the importance of the TIR domain in TIRAP as a key interface involved in protein interactions which could hence serve as a therapeutic target to dampen the extent of acute and chronic inflammatory conditions.


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