From reactive arthritis to rheumatoid arthritis

doi:10.1006/jaut.2000.0496

Journal of Autoimmunity

Volume 16, Issue 3, May 2001, Pages 369-371

https://doi.org/10.1006/jaut.2000.0496 Get rights and content

Abstract

Reactive arthritis was initially described as a sterile synovitis, without microbial components present in the joint tissue. It has, however, become evident that bacterial degradation products, and even bacterial DNA, are present in the synovium of patients with this disease. Since intestinal pathogens are important causes of reactive arthritis, and since cellular homing allows transport of bacterial products from the gut to synovium, we have approached the etiology of rheumatoid arthritis from this point of view. A series of observations has led to a hypothesis that patients with rheumatoid arthritis might favour, for genetic reasons, intestinal bacteria which are capable of inducing arthritis. In the long-run, with continuous seeding of bacterial products from the gut, the synovial inflammation is followed by erosion, exposition of cartilage antigens, and autoimmunity.

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Cited by (38)

Polymyxin B prevents the development of adjuvant arthritis via modulation of TLR/Cox-2 signaling pathway
2020, Life Sciences
Citation Excerpt :
However, Sukhotnik et al. has shown, that one week treatment with MTX was enough to decrease the expression of TLR-4 in gut mucosa [52]. It has now been firmly established that microbial DNA and degradation products are present in inflamed synovium, inducing the production of pro-inflammatory cytokines [53,54]. Studies have also demonstrated that bacterial peptidoglycans could activate synovial fibroblasts through TLR-2 signaling pathway, which is present in the lining layer of synovial tissue, at sites of invasion into bone and cartilage [4,55].
Several microbial toll-like receptor (TLR) ligands, bacterial DNA and bacterial cell wall fragments have been identified in the synovium of rheumatoid arthritis (RA) patients, proving bacterial involvement in the pathogenesis of RA. The current study aimed to verify that low dose polymyxin B could prevent the development of chronic inflammatory arthritis.
Twelve days post adjuvant injection, Sprague-Dawley rats were treated twice weekly with methotrexate (0.5 mg/kg) or daily with polymyxin B (1 mg/kg) or with combination of both for 1 or 2 weeks. Arthritis progression was assessed by hind paw swelling, serum levels of tumor growth factor-1β (TGF-1β), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (HS-CRP) and nuclear factor kappa B (NF-κB) were measured using ELISA. Cyclooxygenase-1 (Cox-1) and Cox-2 activities, as well as mRNA expression of TLR-2 and TLR-4 were determined. Histopathological examination of the ankle joint was performed as well as immunohistochemistry for anti-TLR-4. Histopathological assessment of toxic effects on the kidney was performed.
Adjuvant arthritis led to a significant swelling of the hind paw and alteration in all serum parameters, TLR-2 and TLR-4 expression, as well as Cox-2 activity. These alterations were associated with histopathological changes of the joints. Polymyxin B reduced significantly all biomarkers of inflammation, showing better effect of the combination in most of the studied parameters, with minimal signs of nephrotoxicity.
In conclusion, results showed that polymyxin B possesses significant anti-arthritic activity which may be attributed to inhibition of the TLR-4, NF-κB and Cox-2 signaling pathway.
Rheumatoid arthritis
2019, The Autoimmune Diseases
The joints are a target organ of many systemic autoimmune diseases, but in rheumatoid arthritis (RA), they are the preponderant and mostly sole evident focus of attack, with a large propensity to become destroyed. The pain and damage it elicits underlie the significant disability that can strike the patients and may lead to a wheelchair- or bed-ridden state. Thus RA impairs all aspects of quality of life, including the ability to work, and the consequences of the burden of the disease to the individual and society are enormous. For all these reasons, a better understanding of the pathogenesis of RA to develop new therapeutic agents interfering ideally with all pivotal events in all patients, or finding and abrogating the cause (or causes) of the disease, constitutes a major task.
Protective effects of Paederia scandens extract on rheumatoid arthritis mouse model by modulating gut microbiota
2018, Journal of Ethnopharmacology
Citation Excerpt :
Liu et al. demonstrated sterile mice transplanted with the microbiota from RA mice showed a higher frequency of arthritis induction (Liu et al., 2016), and RA symptoms were alleviated in mice when treated with probiotics (Vaghef-Mehrabany et al., 2014). Also, intestinal bacteria are capable of inducing arthritis by promoting synovial inflammation, mononuclear cell proliferation and TNF-α responses (Toivanen, 2001, 2003; Chen et al., 2002). Paederia scandens (Lour.)
Paederia scandens (Lour.) Merr. (P. scandens) has been traditionally used to treat the pain of rheumatism.
The purpose of this study was to investigate the possible influences of P. scandens on the progression of rheumatoid arthritis (RA), inflammatory responses and gut bacterial communities in RA mouse model.
collagen-induced arthritis (CIA) mice were orally administered with P. scandens extract (PSE) for 24 days. Then, pro-inflammatory cytokine levels in the serum were measured, and gut microbiota was examined with Illumina HiSeq.
Compared with the vehicle group, PSE significantly inhibited paw swelling and reduced arthritis score. Histological examination of ankle soft tissue of demonstrated PSE effectively inhibited the tissue fibrosis and inflammatory cell infiltration. The increased serum levels of TNF-α, IL-1β, IL-6, IL-7, and IL-23 in RA mice were significantly suppressed by PSE. Moreover, PSE treatment help restore gut microbial ecosystem altered in RA mice including decreasing relative abundance of inflammatory related microorganisms, Desulfovibrio, Mucispirillum, Helicobacter, and Lachnospiraceae.
These results suggest that PSE has therapeutic effects in RA mice with CIA, showing the potential as anti-arthritis reagent.
Rheumatoid Arthritis
2013, The Autoimmune Diseases: Fifth Edition
Rheumatoid arthritis (RA) is the most common form of chronic arthritis and the one with the highest propensity to destroy the joints. Autoimmunity is a key feature of RA, manifested primarily by the presence of autoantibodies. The most common autoantibodies are rheumatoid factor (RF; directed against the Fc portion of immunoglobulin G) and antibodies to citrullinated proteins (citrullination being a post-translational modification). They arise many years before disease onset and RF especially is associated with high disease activity and joint damage. Various genetic associations exist, most prominently with class II major histocompatibility complex genes. While the innate and adaptive immune systems are activated and T and B cells appear to play important roles, the common final pathway involves activation of proinflammatory cytokines, magnified by the presence of autoantibodies/immune complexes. Cartilage and bone damage are a consequence of the inflammatory events, the latter mediated by osteoclasts activated within the synovial membrane. Many experimental models of RA exist, but the validity of conclusions drawn thereof can only be ascertained by showing efficacy of respective therapeutic approaches in clinical trials. Indeed, targeting TNF and IL-6, but not IL-1, and B cell depletion or costimulation inhibition are today’s most efficacious therapeutic means. While autoantibodies are of diagnostic and prognostic importance, their most important future strength may be in their role of predicting the occurrence of RA at a pre-clinical stage and allowing for preventive therapeutic intervention.
Pathobiologic mechanisms of chronic obstructive pulmonary disease
2012, Medical Clinics of North America
Citation Excerpt :
For example, smoking is a risk factor for COPD72 and rheumatoid arthritis,116 and there are similarities in the inflammatory cells (neutrophils, macrophages, T lymphocytes) and cytokines (TNF-α, IL-6) involved in both conditions. Moreover, self-perpetuation of the inflammatory response in rheumatoid arthritis joints117 is similar to the continuous airway inflammation observed in COPD lungs even after smoking cessation.110 In support of the “autoimmune” hypothesis, Lee and colleagues118 demonstrated antielastin antibodies in plasma of patients with COPD but not in control subjects.
Pseudosarcoidotic ganglionic mediastinal tuberculosis
2009, Revue de Pneumologie Clinique
L’enquête étiologique devant une granulomatose systémique doit considérer certaines formes rares de l’infection tuberculeuse. Le rhumatisme tuberculeux de Poncet (RTP) en est l’exemple. C’est une entité rare et sujette à controverse.
Un patient de 32 ans a présenté une polyarthrite fébrile avec éruptions cutanées érythématopapulaires. Le bilan a montré un syndrome inflammatoire biologique et des adénopathies médiastinales. Les biopsies pratiquées ont mis en évidence une granulomatose cutanée et ganglionnaire médiastinale. Les lésions cutanées ont spontanément régressé. La culture du prélèvement ganglionnaire était positive au BK. L’évolution était favorable sous traitement antibacillaire avec résolution des signes articulaires en quelques jours.
Le RTP peut être la circonstance de découverte d’une tuberculose viscérale évolutive. Sa connaissance doit faire rechercher une tuberculose devant une granulomatose systémique avec atteinte articulaire et cutanée pouvant simuler une sarcoïdose.
The aetiological inquiry in the presence of systemic granulomatosis should consider some uncommon forms of tuberculosis infections. For instance, Poncet's tuberculous rheumatism is a rare entity subject to controversy.
A 32-year-old man presenting febrile polyarthritis associated with spontaneously vanishing erythematous papular skin rash. The tests revealed a biological inflammatory syndrome and mediastinal lymph nodes. The biopsies showed cutaneous and mediastinal adenoid granulomatosis. The cutaneous lesions resolved spontaneously. The culture of the ganglionic sample was positive. The evolution was favourable under treatment and the articular pain disappeared within a few days.
Poncet's tuberculous rheumatism may underly evolving visceral tuberculosis. It's presence requires a search for tuberculosis when systemic granulomatosis with cutaneous and articular involvement may simulate sarcoidosis.

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^f1: Correspondence to: Paavo Toivanen, Department of Medical Microbiology, Turku University, FIN-20520 Turku, Finland. Tel.: +358-2-333 7426. Fax: +358-2-233 0008. E-mail:[email protected]

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