Dataset Information

HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations.

ABSTRACT: Current evidence supports the concept that reactive arthritis (ReA) is an immune-mediated synovitis resulting from slow bacterial infections and showing intra-articular persistence of viable, non-culturable bacteria and/or immunogenetic bacterial antigens synthesized by metabolically active bacteria residing in the joint and/or elsewhere in the body. The mechanisms that lead to the development of ReA are complex and basically involve an interaction between an arthritogenic agent and a predisposed host. The way in which a host accommodates to invasive facultative intracellular bacteria is the key to the development of ReA. The details of the molecular pathways that explain the articular and extra-articular manifestations of the disease are still under investigation. Several studies have been done to gain a better understanding of the pathogenesis of ReA; these constitute the basis for a more rational therapeutic approach to this disease.

SUBMITTER: Colmegna I

PROVIDER: S-EPMC387405 | biostudies-other | 2004 Apr

REPOSITORIES: biostudies-other

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HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations.

Colmegna Inés I Cuchacovich Raquel R Espinoza Luis R LR

Clinical microbiology reviews 20040401 2

Current evidence supports the concept that reactive arthritis (ReA) is an immune-mediated synovitis resulting from slow bacterial infections and showing intra-articular persistence of viable, non-culturable bacteria and/or immunogenetic bacterial antigens synthesized by metabolically active bacteria residing in the joint and/or elsewhere in the body. The mechanisms that lead to the development of ReA are complex and basically involve an interaction between an arthritogenic agent and a predispose ...[more]

PMID: 15084505

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Project description:Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.

Project description:Alteration of gut microbiota is involved in several chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, and gut microbial "pro-arthritogenic" profiles have been hypothesized. Intestinal inflammation may be involved in spondyloarthropathies and in a subset of patients affected by Juvenile Idiopathic Arthritis (JIA), the most common chronic rheumatic disease of childhood. We compared the fecal microbiota composition of JIA patients with healthy subjects (HS), evaluating differences in microbial profiles between sub-categories of JIA, such as enthesitis-related arthritis (JIA-ERA), in which inflammation of entheses occurs, and polyarticular JIA, non-enthesitis related arthritis (JIA-nERA). Through taxon-level analysis, we discovered alteration of fecal microbiota components that could be involved in subclinical gut inflammation, and promotion of joint inflammation. We observed abundance in Ruminococcaceae in both JIA categories, reduction in Clostridiaceae and Peptostreptococcaceae in JIA-ERA, and increase in Veillonellaceae in JIA-nERA, respectively, compared with HS. Among the more relevant genera, we found an increase in Clostridium cluster XIVb, involved in colitis and arthritis, in JIA-ERA patients compared with HS, and a trend of decrease in Faecalibacterium, known for anti-inflammatory properties, in JIA-nERA compared with JIA-ERA and HS. Differential abundant taxa identified JIA patients for the HLA-B27 allele, including Bilophila, Clostridium cluster XIVb, Oscillibacter, and Parvimonas. Prediction analysis of metabolic functions showed that JIA-ERA metagenome was differentially enriched in bacterial functions related to cell motility and chemotaxis, suggesting selection of potential virulence traits. We also discovered differential microbial profiles and intra-group variability among active disease and remission, suggesting instability of microbial ecosystem in autoimmune diseases with respect to healthy status. Similarly to other chronic autoimmune and inflammatory diseases, different microbial profiles, as observed among different JIA subgroups compared to HS, and potential functional acquisition related to migration, could promote inflammation and contribute to the disease pathogenesis.

Dataset Information

HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations.

Publications

HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations.

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