A study of the roles of some immunological biomarkers in the diagnosis of rheumatoid arthritis.
Journal of medicine and life
Autoimmune rheumatoid arthritis (RA) is a systemic condition closely correlated with a variety of autoantibodies (Abs) that could be considered diagnostic and prognostic markers. The current research was designed to detect the diagnostic values for a number (n) of these auto-Abs in RA detection and to evaluate the accuracy of a combined diagnostic scheme. This prospective study was conducted between September 2021 and August 2022 and included 110 subjects with RA, 70 individuals with other autoimmune disorders as positive controls (PC), and 50 unrelated, apparently healthy individuals as healthy controls (HC). The eligibility criteria for all study groups were followed stringently. An enzyme-linked immunosorbent assay (ELISA) was employed to measure rheumatoid factors (RF), cyclic citrullinated peptide antibodies (CCP-Abs), mutated citrullinated vimentin antibodies (MCV-Abs), anti-perinuclear factor antibodies (APF-Abs), and anti-keratin antibodies (AKA). We calculated the specificity, sensitivity, and predictive values of all auto-Abs. Significantly higher levels of anti-CCP-Abs, anti-MCV-Abs, APF-Abs, and AKAs were reported in the RA patients compared to the HC and PC subjects. RF levels, however, were only statistically elevated when compared to the HC individuals. Anti-APF-Abs had a higher sensitivity rate (70.9%), and anti-CCP-Abs had a higher specificity rate (94.16%) compared to other auto-Abs, whereas the combined detection scheme revealed a higher sensitivity (81.81%) and excellent specificity (90.83%) compared to the two former auto-Abs. Anti-perinuclear factor-Ab was a highly sensitive test, and CCP-Ab was a surpassingly specific assay for identifying RA. Furthermore, the combined detection scheme is an essential serological approach for RA diagnosis and crucial in differentiating this disease from other autoimmune diseases, thus promoting early diagnosis and treatment.
10.25122/jml-2023-0158
Autoantibodies in rheumatoid arthritis - rheumatoid factor, anticitrullinated protein antibodies and beyond.
Current opinion in rheumatology
PURPOSE OF REVIEW:RA is characterized by the presence of autoantibodies among which rheumatoid factors (RFs) and antimodified protein antibodies (AMPA) are serological hallmarks of the disease. In recent years, several novel insights into the biology, immunogenetics and clinical relevance of these autoantibodies have been obtained, which deserve to be discussed in more detail. RECENT FINDINGS:RFs from RA patients seem to target distinct epitopes which appear to be quite specific for RA. Determination of immunoglobulin A (IgA) isotypes of RF and anticitrullinated protein antibodies (ACPA) may provide prognostic information because their presence is associated with reduced therapeutic responses to TNF inhibitors. Furthermore, IgA levels are increased in RA patients and IgA immune complexes are more potent than immunoglobulin G (IgG) complexes in inducing NET formation. Concerning AMPAs, investigations on variable domain glycosylation (VDG) revealed effects on antigen binding and activation of autoreactive B cells. Studies on pathogenetic involvement of ACPA suggest Janus-faced roles: on the one hand, ACPA may be involved in joint destruction and pain perception while on the other hand protective anti-inflammatory effects may be attributed to a subset of ACPAs. SUMMARY:The autoimmune response in RA is extremely complex and still far from being fully understood. Antibodies are not only valuable diagnostic biomarkers but also seem to play pivotal roles in the pathophysiology of RA.
10.1097/BOR.0000000000001006
The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting.
Nature reviews. Immunology
Patients with rheumatoid arthritis can be divided into two major subsets characterized by the presence versus absence of antibodies to citrullinated protein antigens (ACPAs) and of rheumatoid factor (RF). The antibody-positive subset of disease, also known as seropositive rheumatoid arthritis, constitutes approximately two-thirds of all cases of rheumatoid arthritis and generally has a more severe disease course. ACPAs and RF are often present in the blood long before any signs of joint inflammation, which suggests that the triggering of autoimmunity may occur at sites other than the joints (for example, in the lung). This Review summarizes recent progress in our understanding of this gradual disease development in seropositive patients. We also emphasize the implications of this new understanding for the development of preventive and therapeutic strategies. Similar temporal and spatial separation of immune triggering and clinical manifestations, with novel opportunities for early intervention, may also occur in other immune-mediated diseases.
10.1038/nri.2016.124
Anti-CCP biosensors in rheumatoid arthritis.
Clinica chimica acta; international journal of clinical chemistry
Biosensors are unique analytical tools for the detection of biomarkers. Of these, autoantibodies against citrullinated proteins (ACPA) are useful for the differential diagnosis of rheumatoid arthritis (RA). The autoantibodies may be detected by immunoassay technology using synthetic cyclic citrullinated peptides (CCP), ie, anti-CCP. Recently, several biosensors have been developed for anti-CCP using CCP and mutated citrullinated vimentin (MCV) as recognition elements. In this review we highlight all currently available ACPA biosensor technology including those based on fluorescence, chemiluminescence, electrochemiluminescence (ECL), surface-enhanced Raman scattering (SERS)-based, surface plasmon resonance (SPR), lateral flow immunoassays (LFIA), and electrochemical. We explore various peptides as recognition elements, electrode modifiers and signal amplification systems thus providing new opportunities for next-generation biosensor design in RA.
10.1016/j.cca.2024.119767
New biomarkers in rheumatoid arthritis.
Willemze A,Toes R E M,Huizinga T W J,Trouw L A
The Netherlands journal of medicine
Rheumatoid arthritis (RA) is a common autoimmune disease affecting around 1% of the population. Although major advances have been made in the treatment of RA, still relatively little is known on disease pathogenesis and aetiology. From treatment studies it has become clear that treating patients early in their disease course will provide the best results. However, especially in the early phase of arthritis, in particular when the patients do not yet fulfil the criteria for RA, it is difficult to decide which patients would benefit most from an early and aggressive intervention. Good biomarkers are important to guide decisions in the clinical management of RA. Next to the well-known rheumatoid factor (RF) and the anti-citrullinated protein antibodies (ACPA), several new markers are now likely to become available with interesting potential. Besides antibody responses directed against citrullinated proteins, also antibodies against carbamylated proteins (anti-CarP) have recently been shown to be present in RA. Interestingly these anti-CarP antibodies are also present in around 20% of the ACPA-negative RA patients and are associated with more severe joint damage in this group. Apart from the antibodies that help in establishing the diagnosis and prognosis, also novel biomarkers that reflect clinical disease activity scores are being discovered. The development of biomarker-based disease activity scores might allow easy and frequent monitoring of patients to rapidly adjust treatment.
How to investigate: Pre-clinical rheumatoid arthritis.
Martins Patrícia,Fonseca João Eurico
Best practice & research. Clinical rheumatology
Multiple studies have shown that there is a pre-clinical period preceding the development of rheumatoid arthritis (RA). During this period, complex interactions between the environmental and genetic causes occur, and the expression "preclinical RA" has been proposed to define it. Early treatment intervention is associated with less joint damage and has an increased possibility of achieving remission. In this review, we provide an overview of the preclinical phases of RA, new immunological and imaging biomarkers, and the clinical features, and the management of individuals at-risk of developing RA.
10.1016/j.berh.2019.101438
Role of Liquid Biopsies in Rheumatoid Arthritis.
Methods in molecular biology (Clifton, N.J.)
Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by genetic and environmental factors. Early diagnosis is crucial for effective therapy and prognosis of RA, while biomarkers play important roles in early diagnosis. Traditional laboratory tests include rheumatoid factor, anti-cyclic citrullinated peptide antibody, which are inadequate in the ability of early diagnosis. Liquid biopsy technology is a technique using biomarkers found in the blood, urine, and other biological samples from patients, including DNA, RNA, exosome, etc. Evidence indicates that these biomarkers are involved in pathological and physiological conditions of RA. We reviewed the effects of liquid biopsy technology in the early diagnosis of RA and may provide new ideas for effective and precise treatment.
10.1007/978-1-0716-3346-5_16
Pathophysiology and stratification of treatment-resistant rheumatoid arthritis.
Immunological medicine
Early diagnosis and timely therapeutic intervention are clinical challenges of rheumatoid arthritis (RA), especially for treatment-resistant or difficult-to-treat patients. Little is known about the immunological mechanisms involved in refractory RA. In this review, we summarize previous research findings on the immunological mechanisms of treatment-resistant RA. Genetic prediction of treatment-resistant RA is challenging. Patients with and without anti-cyclic citrullinated peptide autoantibodies are considered part of distinct subgroups, especially regarding long-term clinical prognosis and treatment responses. B cells, T cells and other immune cells and fibroblasts are of pathophysiological importance and are associated with treatment responses. Finally, we propose a new hypothesis that stratifies patients with RA into two subgroups with distinct immunological pathologies based on our recent immunomics analysis of RA. One RA subgroup with a favorable prognosis is characterized by increased interferon signaling. Another subgroup with a worse prognosis is characterized by enhanced acquired immune responses. Increases in dendritic cell precursors and diversified autoreactive anti-modified protein antibodies may have pathophysiological roles, especially in the latter subgroup. These findings that improve treatment response predictions might contribute to future precision medicine for RA.
10.1080/25785826.2023.2235734
Shift in perspective: autoimmunity protecting against rheumatoid arthritis.
Annals of the rheumatic diseases
A hallmark of rheumatoid arthritis (RA) is the increased levels of autoantibodies preceding the onset and contributing to the classification of the disease. These autoantibodies, mainly anti-citrullinated protein antibody (ACPA) and rheumatoid factor, have been assumed to be pathogenic and many attempts have been made to link them to the development of bone erosion, pain and arthritis. We and others have recently discovered that most cloned ACPA protect against experimental arthritis in the mouse. In addition, we have identified suppressor B cells in healthy individuals, selected in response to collagen type II, and these cells decrease in numbers in RA. These findings provide a new angle on how to explain the development of RA and maybe also other complex autoimmune diseases preceded by an increased autoimmune response.
10.1136/ard-2023-225237
Anti-Golgi Antibody as a Potential Indicator for Rheumatoid Arthritis.
Zhai Jianzhao,Liao Jing,Wang Minjin,Huang Zhuochun,Hu Jing,Xu Huan,Xie Qibing,Ma Bin,Baan Carla C,Wu Yongkang
Laboratory medicine
OBJECTIVE:To reveal the relationship between anti-Golgi antibody (AGA) and clinical diseases through retrospective analysis. METHODS:The clinical data of 584 cases testing positive for AGA in the past 11 years were collected and retrospectively analyzed. RESULTS:AGA pattern accounted for .2% of positive ANA results. In total, 35.0% of diagnosed patients had autoimmune diseases (AID), mainly rheumatoid arthritis (RA). High-titer AGA (≧1:1000) was common in AID. In nondiagnosed patients with clinical symptoms, joint pain/muscle pain was the most common. CONCLUSIONS:Positive AGA with high titer was closely related to RA. Joint pain/muscle pain was the most common symptom in patients who tested AGA positive. Therefore, AGA may be a key indicator of RA in the Chinese population.
10.1093/labmed/lmab046
Preclinical Rheumatoid Arthritis and Rheumatoid Arthritis Prevention.
Deane Kevin D
Current rheumatology reports
PURPOSE OF REVIEW:This review is to provide an update on the current understanding of rheumatoid arthritis (RA) development related to disease development prior to the onset clinically apparent synovitis and opportunities for disease prevention. RECENT FINDINGS:A growing number of studies have demonstrated that serum elevations of autoantibodies rheumatoid factor and antibodies to citrullinated protein/peptide antigens (ACPA) are highly predictive of future development of IA/RA. This has underpinned the development of several prevention trials in RA. The full results from most of these prevention trials are pending, but ultimately, they should further inform several critical issues in RA prevention including identification and enrollment of individuals at high risk of imminent RA, the efficacy, safety and cost-effectiveness of prevention, and potentially the identification of new targets for prevention. Results from studies in RA prevention as well as other ongoing natural history studies of RA will help to change the paradigm of how RA is managed, potentially adding prevention to the possibilities for management.
10.1007/s11926-018-0754-0
Insights of rheumatoid arthritis biomarkers.
Kolarz Bogdan,Podgorska Dominika,Podgorski Rafal
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
Rheumatoid arthritis is a chronic, autoimmune connective tissue disease. In addition to joint involvement, extra-articular changes and organ complications also occur in the course of the disease. Untreated disease leads to disability and premature death. Therefore, it is important to recognise and begin treatment early. Based on the presence of rheumatoid factor and antibodies against citrullinated peptides, we can distinguish two forms of the disease: seropositive and seronegative. Research continues to elucidate the mechanisms of the onset of the disease, as well as to uncover factors that induce and influence the activity of the disease. The presence of markers that initially appear and affect the course of the disease can potentially aid in patient treatment. In this article, we have collected biomarkers of rheumatoid arthritis that are well understood as well as those that have been recently described.
10.1080/1354750X.2020.1794043
Is rheumatoid arthritis an autoimmune disease?
Chemin Karine,Klareskog Lars,Malmström Vivianne
Current opinion in rheumatology
PURPOSE OF REVIEW:Rheumatoid arthritis (RA) is not a homogenous disease entity but a syndrome with different causes and abnormalities with shared clinical manifestations. One major subset is anticitrullinated protein antibody (ACPA)-positive RA, which represents the larger fraction of RA patients and where autoantibodies and HLA class II association implicate an autoimmune condition. In the past few years, the specificity of the ACPA response and the possibility to subdivide patients based on ACPA subgroups have received much attention whereas the effector functions of the autoantibodies and underlying lymphocytes have not. RECENT FINDINGS:The review, based on HLA, will discuss the generation of the autoreactive citrulline-specific T-cell repertoire, highlight our current understanding of T-cell specificities and effector functions of both the T cells and ACPAs. SUMMARY:Dividing RA into subsets has only influenced clinical practice to a limited degree, that is, by indicating a better response to therapies modulating adaptive immunity, such as rituximab, in the ACPA+ disease subset. A more detailed understanding of the immune reactions underlying various subsets of RA may, however, change our view on RA therapeutics and prevention with the assumption that autoimmune variants of RA should be both curable and preventable.
10.1097/BOR.0000000000000253
Autoantibody-negative rheumatoid arthritis: still a challenge for the rheumatologist.
The Lancet. Rheumatology
Increased research over the past 30 years has greatly improved the understanding of the pathophysiological mechanisms and clinical aspects of autoantibody-positive rheumatoid arthritis, resulting in improved management and outcomes. In contrast, the subset of rheumatoid arthritis that does not have autoantibodies (such as rheumatoid factor and anti-citrullinated protein autoantibodies) remains less well defined in its pathogenic mechanisms. Autoantibody-negative rheumatoid arthritis continues to pose diagnostic challenges, might respond differently to therapies, and appears to be burdened with different comorbidities and outcomes. The clear separation of rheumatoid arthritis according to serotypes is still a subject of uncertainty and controversy, and studies specifically focused on comparing rheumatoid arthritis and rheumatoid arthritis-like arthritides that do not have autoantibodies remain scarce. The purpose of this Review is to summarise the peculiarities that make autoantibody-negative rheumatoid arthritis different from its autoantibody-positive counterpart, with the aim of generating debate and stimulating further research on this challenging condition.
10.1016/S2665-9913(23)00242-4
From Rheumatoid Factor to Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies for Diagnosis and Prognosis Prediction in Patients with Rheumatoid Arthritis.
Wu Chao-Yi,Yang Huang-Yu,Luo Shue-Fen,Lai Jenn-Haung
International journal of molecular sciences
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease mainly involving synovial inflammation and articular bone destruction. RA is a heterogeneous disease with diverse clinical presentations, prognoses and therapeutic responses. Following the first discovery of rheumatoid factors (RFs) 80 years ago, the identification of both anti-citrullinated protein antibodies (ACPAs) and anti-carbamylated protein antibodies (anti-CarP Abs) has greatly facilitated approaches toward RA, especially in the fields of early diagnosis and prognosis prediction of the disease. Although these antibodies share many common features and can function synergistically to promote disease progression, they differ mechanistically and have unique clinical relevance. Specifically, these three RA associating auto-antibodies (autoAbs) all precede the development of RA by years. However, while the current evidence suggests a synergic effect of RF and ACPA in predicting the development of RA and an erosive phenotype, controversies exist regarding the additive value of anti-CarP Abs. In the present review, we critically summarize the characteristics of these autoantibodies and focus on their distinct clinical applications in the early identification, clinical manifestations and prognosis prediction of RA. With the advancement of treatment options in the era of biologics, we also discuss the relevance of these autoantibodies in association with RA patient response to therapy.
10.3390/ijms22020686
Pre-RA: Can early diagnosis lead to prevention?
Best practice & research. Clinical rheumatology
Rheumatoid arthritis (RA) is currently diagnosed and treated once an individual displays the clinical findings of inflammatory arthritis (IA). However, growing evidence supports that there is a 'pre-RA' stage that can be identified through factors such as autoantibodies in absence of clinically apparent IA. In particular, biomarkers, including antibodies to citrullinated protein antigens (ACPA), demonstrate a high risk for future IA/RA, and multiple clinical trials have been developed to intervene in individuals in pre-RA to prevent or delay clinically apparent disease. Herein, we will discuss in more depth what is currently known about the natural history of RA, and the emerging possibility that early 'diagnosis' of RA-related autoimmunity followed by an intervention can lead to the delay or prevention of the first onset of clinically apparent RA.
10.1016/j.berh.2021.101737
[Rheumatoid Arthritis].
Therapeutische Umschau. Revue therapeutique
Rheumatoid Arthritis Rheumatoid Arthritis (RA) is the most frequent chronic inflammatory joint disease with a prevalence of approximately 1% worldwide. The pathogenesis is a complex interplay of genetic, epigenetic, and environmental factors, which are still incompletely understood. The disease is characterized by a polyarticular synovitis with symmetrical involvement of small and large joints. The majority of patients has detectable autoantibodies in the serum, rheumatoid factor and anti-CCP antibodies which are specific for RA. The uncontrolled chronic joint inflammation results in destructive changes of joint cartilage and bone. An early diagnosis and initiation of treatment is therefore of central importance. Disease-modifying anti-rheumatic drugs (DMARD) are able to inhibit joint destruction and should be started as soon as possible. Therapy should be targeted to reach a state of remission. The introduction of highly effective biologic and targeted synthetic DMARD has allowed to reach this goal of therapy in many patients and to prevent disability. However, risks of medication need to be considered, as well as comorbidities.
10.1024/0040-5930/a001403
Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings.
Clinical reviews in allergy & immunology
Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA ("seropositive") in general display a different etiology and disease course compared to so-called "seronegative" patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.
10.1007/s12016-021-08890-1
The pre-clinical phase of rheumatoid arthritis: From risk factors to prevention of arthritis.
Petrovská Nora,Prajzlerová Klára,Vencovský Jiří,Šenolt Ladislav,Filková Mária
Autoimmunity reviews
Rheumatoid arthritis (RA) is a chronic autoimmune disease considered as a multistep process spanning from the interaction of genetic (e.g., shared epitope or non-HLA loci), environmental and behavioral risk factors (e.g., smoking) leading to breaking immune tolerance and autoimmune processes such as the production of autoantibodies (e.g., antibodies against citrullinated proteins ACPA or rheumatoid factors, RF), development of the first symptoms without clinical arthritis, and, finally, the manifestation of arthritis. Despite the typical joint involvement in established RA, the pathogenesis of the disease likely begins far from joint structures: in the lungs or periodontium in association with citrullination, intestinal microbiome, or adipose tissue, which supports normal findings in synovial tissue in ACPA+ patients with arthralgia. The presence of ACPA is detectable even years before the first manifestation of RA. The pre-clinical phase of RA is the period preceding clinically apparent RA with ACPA contributing to the symptoms without subclinical inflammation. While the combination of ACPA and RF increases the risk of progression to RA by up to 10 times, increasing numbers of novel autoantibodies are to be investigated to contribute to the increased risk and pathogenesis of RA. With growing knowledge about the course of RA, new aspiration emerges to cure and even prevent RA, shifting the "window of opportunity" to the pre-clinical phases of RA. The clinical definition of individuals at risk of developing RA (clinically suspect arthralgia, CSA) makes it possible to unify these at-risk individuals' clinical characteristics for "preventive" treatment in ongoing clinical trials using mostly biological or conventional synthetic disease-modifying drugs. However, the combination of symptoms, laboratory, and imaging biomarkers may be the best approach to select the correct target at-risk population. The current review aims to explore different phases of RA and discuss the potential of (non)pharmacological intervention aiming to prevent RA.
10.1016/j.autrev.2021.102797
Preclinical rheumatoid arthritis and rheumatoid arthritis prevention.
Current opinion in rheumatology
PURPOSE OF REVIEW:This review is to provide an update on the current understanding of rheumatoid arthritis (RA) development related to disease development prior to the onset clinically apparent synovitis (i.e. Pre-RA), and opportunities for disease prevention. RECENT FINDINGS:A growing number of studies have demonstrated that serum elevations of autoantibodies rheumatoid factor, antibodies to citrullinated protein/peptide antigens (ACPAs) and antibodies to other posttranslationally modified proteins (e.g. carbamylated proteins) are highly predictive of future development of inflammatory arthritis/RA during a period that can be termed Pre-RA. Other factors including genetic, environmental, symptoms and imaging findings can also enhance prediction. Moreover, several novel biomarkers and changes in autoantibodies (e.g. glycosylation of variable domains) have been identified in Pre-RA. There has also been growing evidence that initiation and propagation of RA-related autoimmunity during the Pre-RA phase may be related to mucosal processes. The discovery of Pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent IA in at-risk individuals. Additional studies are evaluating the ability of drugs including abatacept, hydroxychloroquine and methotrexate to prevent or delay future RA. SUMMARY:The results from ongoing natural history and prevention trials in RA should further inform several critical issues in RA prevention including identification and enrolment of individuals at high-risk of imminent RA, the efficacy, safety and cost-effectiveness of prevention, and potentially the identification of new targets for prevention.
10.1097/BOR.0000000000000708
An overview of autoantibodies in rheumatoid arthritis.
van Delft Myrthe A M,Huizinga Tom W J
Journal of autoimmunity
Rheumatoid arthritis (RA) is a systemic auto-immune disease principally effecting synovial joints. RA is characterized by immune cell infiltration in the joint. The presence of autoantibodies is a hallmark for the disease, among these are rheumatoid factor and antibodies against post-translational modified proteins like citrullination (ACPA) and carbamylation (anti-CarP antibodies). These autoantibodies may form immune complexes in the joint, leading to the attraction of immune cells. Based on the presence of these autoantibodies, RA patients can be subdivided in autoantibody positive and negative disease. Both subsets can be associated with genetic and environmental risk factors for RA, like the human leukocyte antigen (HLA) allele and smoking. Autoantibodies can already be detected years before disease onset in a subgroup of patients and at symptom onset a broad isotype spectrum is observed. This suggests that various events occur prior to the development of RA in which the first autoantibodies develop in predisposed individuals. Therefore, the presence of these autoantibodies can be useful in predicting future RA patients. Research on the characteristics and effector function of these autoantibodies is ongoing and will give more knowledge in the inflammatory responses underlying RA. This will give insight in the pathogenic role of autoantibodies in RA. Recent data are suggestive of a role for mucosal surfaces in the development of auto-immune responses associated with (the development of) RA. In conclusion, investigating the potential pathogenic effector functions of autoantibody isotypes and their molecular- and physicochemical-compositions might improve understanding of the disease origin and its underlying immunological processes. This may lead to the development of new therapeutic targets and strategies.
10.1016/j.jaut.2019.102392
Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies.
Mueller Anna-Lena,Payandeh Zahra,Mohammadkhani Niloufar,Mubarak Shaden M H,Zakeri Alireza,Alagheband Bahrami Armina,Brockmueller Aranka,Shakibaei Mehdi
Cells
Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, and bone erosion. To prevent joint damage and physical disability as one of many symptoms of RA, early diagnosis is critical. Auto-antibodies play a pivotal clinical role in patients with systemic RA. As biomarkers, they could help to make a more efficient diagnosis, prognosis, and treatment decision. Besides auto-antibodies, several other factors are involved in the progression of RA, such as epigenetic alterations, post-translational modifications, glycosylation, autophagy, and T-cells. Understanding the interplay between these factors would contribute to a deeper insight into the causes, mechanisms, progression, and treatment of the disease. In this review, the latest RA research findings are discussed to better understand the pathogenesis, and finally, treatment strategies for RA therapy are presented, including both conventional approaches and new methods that have been developed in recent years or are currently under investigation.
10.3390/cells10113017
The etiology of rheumatoid arthritis.
Scherer Hans Ulrich,Häupl Thomas,Burmester Gerd R
Journal of autoimmunity
Rheumatoid arthritis is a heterogeneous disease, which can be, based on data combining genetic risk factors and autoantibodies, sub-classified into ACPA-positive and -negative RA. Presence of ACPA and RF as well as rising CRP-levels in some patients years before onset of clinical symptoms indicate that relevant immune responses for RA development are initiated very early. ACPA are highly specific for RA, whereas RF can also be found among healthy (elderly) individuals and patients with other autoimmune diseases or infection. The most important genetic risk factor for RA development, the shared epitope alleles, resides in the MHC class II region. Shared epitope alleles, however, only predispose to the development of ACPA-positive RA. Smoking is thus far the most important environmental risk factor associated with the development of RA. Studies on synovitis have shown the importance not only of adaptive but also of innate immune responses. In summary of the various results from immunological changes in blood and synovial tissue, the extension of the immune response from a diffuse myeloid to a lympho-myeloid inflammation appears to be associated with a more successful therapeutic response to biologics. With respect to advances in synovitis research, new targets for treatment against pathological subsets of immune cells or fibroblasts are already on the horizon. However, alternative strategies involving the microbiome may play an important role as well and research in this field is growing rapidly.
10.1016/j.jaut.2019.102400