Correlation of Lyme Disease–Associated IgG4 Autoantibodies With Synovial Pathology in Antibiotic‐Refractory Lyme Arthritis

Sulka, Katherine B.; Strle, Klemen; Crowley, Jameson T.; Lochhead, Robert B.; Anthony, Robert M.; Steere, Allen C.

doi:10.1002/art.40566

Cited by 14 publications

(13 citation statements)

References 43 publications

(67 reference statements)

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“…These four self‐proteins are abundant in postinfectious LA synovial tissue and are involved in tissue damage and/or wound repair. During both active infection and in the postinfectious LA phase, subsets of patients have autoantibody responses to one or more of these autoantigens, and in the postinfectious phase, these autoantibodies correlate with specific aspects of synovial histology (Sulka et al, ). Moreover, patients with postinfectious LA often develop autoreactive T‐cell responses, and it is still unclear why the IFNγ‐producing T cells are abundant in synovial tissue during the postinfectious phase, when spirochetes are no longer present, or whether these autoimmune responses have a role in perpetuating the disease.…”

Section: Discussionmentioning

confidence: 99%

Interferon‐gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast‐like synoviocytes into immune effector cells

Lochhead

Ordóñez

Arvikar

et al. 2019

Cellular Microbiology

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Lyme arthritis (LA), a late disease manifestation of Borrelia burgdorferi infection, usually resolves with antibiotic therapy. However, some patients develop proliferative synovitis lasting months to several years after spirochetal killing, called postinfectious LA. In this study, we phenotyped haematopoietic and stromal cell populations in the synovial lesion ex vivo and used these findings to generate an in vitro model of LA using patient‐derived fibroblast‐like synoviocytes (FLS). Ex vivo analysis of synovial tissue revealed high abundance of IFNγ‐producing T cells and NK cells. Similar to marked IFNγ responses in tissue, postinfectious LA synovial fluid also had high levels of IFNγ. HLA‐DR‐positive FLS were present throughout the synovial lesion, particularly in areas of inflammation. FLS stimulated in vitro with B. burgdorferi, which were similar to conditions during infection, expressed 68 genes associated primarily with innate immune activation and neutrophil recruitment. In contrast, FLS stimulated with IFNγ, which were similar to conditions in the postinfectious phase, expressed >2,000 genes associated with pathogen sensing, inflammation, and MHC Class II antigen presentation, similar to the expression profile in postinfectious synovial tissue. Furthermore, costimulation of FLS with B. burgdorferi and IFNγ induced greater expression of IL‐6 and other innate immune response proteins and genes than with IFNγ stimulation alone. These results suggest that B. burgdorferi infection, in combination with IFNγ, initiates the differentiation of FLS into a highly inflammatory phenotype. We hypothesise that overexpression of IFNγ by lymphocytes within synovia perpetuates these responses in the postinfectious period, causing proliferative synovitis and stalling appropriate repair of damaged tissue.

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Section: Discussionmentioning

confidence: 99%

Interferon‐gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast‐like synoviocytes into immune effector cells

Lochhead

Ordóñez

Arvikar

et al. 2019

Cellular Microbiology

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“…These antibodies to self-antigens are generally of the IgG2 and IgG4 subclasses, whereas those directed against B. burgdorferi antigens are usually IgG1 and IgG3 (Sulka et al, 2018). Interestingly, the magnitude of IgG4 to some of these self-antigens correlates with the degree of obliterative vasculopathy and fibrosis characteristic of post-antibiotic Lyme arthritis (Londono et al, 2014;Sulka et al, 2018).…”

Section: Return To Homeostasis and Immunoregulationmentioning

confidence: 99%

Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes

Wooten¹,

Baumgarth²

2022

Current Issues in Molecular Biology

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The mammalian host responds to infection with Borrelia spirochetes through a highly orchestrated immune defense involving innate and adaptive effector functions aimed toward limiting pathogen burdens, minimizing tissue injury, and preventing subsequent reinfection. The evolutionary adaptation of Borrelia spirochetes to their reservoir mammalian hosts may allow for its persistence despite this immune defense. This review summarizes our current understanding of the host immune response to B. burgdorferi sensu lato, the most widely studied Borrelia spp. and etiologic agent of Lyme borreliosis. Pertinent literature will be reviewed with emphasis on in vitro, ex vivo and animal studies that influenced our understanding of both the earliest responses to B. burgdorferi as it enters the mammalian host and those that evolve as spirochetes disseminate and establish infection in multiple tissues. Our focus is on the immune response of inbred mice, the most commonly studied animal model of B. burgdorferi infection and surrogate for one of this pathogen's principle natural reservoir hosts, the white-footed deer mouse. Comparison will be made to the immune responses of humans with Lyme borreliosis. Our goal is to provide an understanding of the dynamics of the mammalian immune response during infection with B. burgdorferi and its relation to the outcomes in reservoir (mouse) and non-reservoir (human) hosts.Curr. Issues . caister.com/cimb caister.com/cimb 145 Curr. Issues Mol. Biol. Vol. 42 Immune Response to Borrelia Bockenstedt et al.

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“…The levels of cytokine and chemokine in serum were lower than in synovial fluid, and the values were similar in the responsive and refractory groups. The only serum levels of IL-4 in the refractory group was significantly higher [13]. Analysis of peripheral blood mononuclear cells (PBMCs) from patients with Lyme arthritis showed, that B. burgdorferi can induce the production of chemokines e.g.…”

Section: Discussionmentioning

confidence: 99%

“…As reported by Petnicki-Ocwieja et al: 'MARCO was significantly up-regulated on B. burgdorferi stimulation, and the up-regulation of MARCO was dependent on MyD88, and MARCO deficient macrophage showed a decrease in the phagocytosis of B. burgdorfer' [11]. Spirochetes activate proteolytic enzymes, including matrix metallproteinases (MMPs), which are involved in the degradation of protein components of the extracellular matrix and in degenerative processes which, in turn, induce activation or inactivation of cytokines and chemokines [12,13,14,15].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the concentration of selected serological parameters in patients undergoing antibiotic treatment of Lyme disease and assessment of their potential application in the control of the therapy effectiveness – pilot study

Tokarska-Rodak¹,

Fota-Markowska²,

Pańczuk³

et al. 2021

Ann Agric Environ Med.

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Correlation of Lyme Disease–Associated IgG4 Autoantibodies With Synovial Pathology in Antibiotic‐Refractory Lyme Arthritis

Cited by 14 publications

References 43 publications

Interferon‐gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast‐like synoviocytes into immune effector cells

Interferon‐gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast‐like synoviocytes into immune effector cells

Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes

Analysis of the concentration of selected serological parameters in patients undergoing antibiotic treatment of Lyme disease and assessment of their potential application in the control of the therapy effectiveness – pilot study

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