Lyme disease, which is epidemic in certain communities, primarily in the northeastern United States, is caused by the tick-borne spirochete Borrelia burgdorferi (also called Borreliella burgdorferi). ...When untreated, the disease usually occurs in stages with different manifestations at each stage (1). In the northeastern United States, the infection usually begins with a slowly expanding skin lesion, erythema migrans (stage 1), often accompanied by nonspecific symptoms, including headache, myalgias, arthralgias, fever, malaise, and fatigue. Within weeks (stage 2), neurologic or cardiac abnormalities may develop. Months later (stage 3), usually following a latent period, intermittent or persistent monoarticular or oligoarticular arthritis commonly develops, lasting for several years, accompanied by minimal, if any, systemic symptoms. The consequences of this excessive proinflammatory response in Lyme synovia include vascular damage, autoimmune and cytotoxic processes, and fibroblast proliferation and fibrosis (4). An important driver of innate immune responses may be persistence of B. burgdorferi peptidoglycan in synovial fluid, which may be especially difficult to clear.
Lyme borreliosis is caused by a growing list of related, yet distinct, spirochetes with complex biology and sophisticated immune evasion mechanisms. It may result in a range of clinical ...manifestations involving different organ systems, and can lead to persistent sequelae in a subset of cases. The pathogenesis of Lyme borreliosis is incompletely understood, and laboratory diagnosis, the focus of this review, requires considerable understanding to interpret the results correctly. Direct detection of the infectious agent is usually not possible or practical, necessitating a continued reliance on serologic testing. Still, some important advances have been made in the area of diagnostics, and there are many promising ideas for future assay development. This review summarizes the state of the art in laboratory diagnostics for Lyme borreliosis, provides guidance in test selection and interpretation, and highlights future directions.
Diagnosis and treatment of Lyme arthritis Arvikar, Sheila L; Steere, Allen C
Infectious disease clinics of North America,
06/2015, Letnik:
29, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In the United States, Lyme arthritis is the most common feature of late-stage Borrelia burgdorferi infection, usually beginning months after the initial bite. In some, earlier phases are asymptomatic ...and arthritis is the presenting manifestation. Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in 1 or a few large joints. Serologic testing is the mainstay of diagnosis. Synovial fluid polymerase chain reaction for B burgdorferi DNA is often positive before treatment, but is not a reliable marker of spirochetal eradication after therapy. This article reviews the clinical manifestations, diagnosis, and management of Lyme arthritis.
Objective
Prevotella copri, an intestinal microbe, may overexpand in stool samples from patients with new‐onset rheumatoid arthritis (RA), but it is not yet clear whether the organism has immune ...relevance in RA pathogenesis.
Methods
HLA–DR–presented peptides (T cell epitopes) from P copri were sought directly in the patients' synovial tissue or peripheral blood mononuclear cell (PBMC) samples using tandem mass spectrometry. The antigenicity of peptides or their source proteins was examined in samples from the RA patients or comparison groups. T cell reactivity was determined by enzyme‐linked immunospot assay; antibody responses were measured by enzyme‐linked immunosorbent assay, and cytokine/chemokine determinations were made by bead‐based assays. Serum and synovial fluid samples were examined for 16S ribosomal DNA for P copri using nested polymerase chain reaction analysis.
Results
In PBMCs, we identified an HLA–DR–presented peptide from a 27‐kd protein of P copri (Pc‐p27), which stimulated Th1 responses in 42% of patients with new‐onset RA. In both new‐onset RA patients and chronic RA patients, 1 subgroup had IgA antibody responses to either Pc‐p27 or the whole organism, which correlated with Th17 cytokine responses and frequent anti–citrullinated protein antibodies (ACPAs). The other subgroup had IgG P copri antibodies, which were associated with Prevotella DNA in synovial fluid, P copri–specific Th1 responses, and less frequent ACPAs. In contrast, P copri antibody responses were rarely found in patients with other rheumatic diseases or in healthy controls.
Conclusion
Subgroups of RA patients have differential IgG or IgA immune reactivity with P copri, which appears to be specific for this disease. These observations provide evidence that P copri is immune‐relevant in RA pathogenesis.
Background. Tests to determine serum antibody levels—the 2-tier sonicate immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and Western blot method or the IgG ...of the variable major protein-like sequence-expressed (VlsE) sixth invariant region (C6) peptide ELISA method— are the major tests available for support of the diagnosis of Lyme disease. However, these tests have not been assessed prospectively. Methods. We used these tests prospectively to determine serologic responses in 134 patients with various manifestations of Lyme disease, 89 patients with other illnesses (with or without a history of Lyme disease), and 136 healthy subjects from areas of endemicity and areas in which the infection was not endemic. Results. With 2-tier tests and the C6 peptide ELISA, only approximately one-third of 76 patients with erythema migrans had results that were positive for IgM or IgG seroreactivity with Borrelia burgdorferi in acute-phase samples. During convalescence, 3–4 weeks later, almost two-thirds of patients had seroreactivity with the spirochete B. burgdorferi. The frequencies of seroreactivity were significantly greater among patients with spirochetal dissemination than they were among those who lacked evidence of disseminated disease. Of the 44 patients with Lyme disease who had neurologic, heart, or joint involvement, all had positive C6 peptide ELISA results, 42 had IgG responses with 2-tier tests, and 2 patients with facial palsy had only IgM responses. However, among the control groups, the IgG Western blot was slightly more specific than the C6 peptide ELISA. The differences between the 2 test systems (2-tier testing and C6 peptide ELISA) with respect to sensitivity and specificity were not statistically significant. Conclusions. Except in patients with erythema migrans, both test systems were sensitive for support of the diagnosis of Lyme disease. However, with current methods, 2-tier testing was associated with slightly better specificity.
Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an ...expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31Suppl 1:1–14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post–Lyme disease syndrome is proposed.
Borrelia burgdorferi sensu stricto isolates from patients with erythema migrans in Europe and the United States were compared by genotype, clinical features of infection, and inflammatory potential. ...Analysis of outer surface protein C and multilocus sequence typing showed that strains from these 2 regions represent distinct genotypes. Clinical features of infection with B. burgdorferi in Slovenia were similar to infection with B. afzelii or B. garinii, the other 2 Borrelia spp. that cause disease in Europe, whereas B. burgdorferi strains from the United States were associated with more severe disease. Moreover, B. burgdorferi strains from the United States induced peripheral blood mononuclear cells to secrete higher levels of cytokines and chemokines associated with innate and Th1-adaptive immune responses, whereas strains from Europe induced greater Th17-associated responses. Thus, strains of the same B. burgdorferi species from Europe and the United States represent distinct clonal lineages that vary in virulence and inflammatory potential.
In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect ...HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels. FLNA did not show the same results. The HLA-DR-presented GNS peptide has marked sequence homology with epitopes from sulfatase proteins of the Prevotella sp. and Parabacteroides sp., whereas the HLA-DR-presented FLNA peptide has homology with epitopes from proteins of the Prevotella sp. and Butyricimonas sp., another gut commensal. Patients with T cell reactivity with each self-peptide also had responses to the corresponding microbial peptides, and the levels were directly correlated. Furthermore, HLA-DR molecules encoded by shared-epitope (SE) alleles were predicted to bind these self- and microbial peptides strongly, and these responses were more common in RA patients with SE alleles. Thus, sequence homology between T cell epitopes of 2 self-proteins and a related order of gut microbes may provide a link between mucosal and joint immunity in patients with RA.
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