Lyme disease

A selection of scientific research from around the world is presented here, correlating rheumatoid arthritis (RA) to the infectious cause of Lyme disease, Borrelia burgdorferi (Bb), a tick-borne pleomorphic organism possessing extraordinary abilites to persist and cloak itself from the immune system. Cumulative science-based evidence continues to emerge that points to significant auto-immunologic reactions to this infection in the human and animal host, confirmed by histopathology and serology, as well as by clinically-observed presentations.


Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme DiseaseArthritis Rheumatol. 2017 Jan;69(1):194-202.

Recognition by Massachusetts General Hospital researchers that rheumatic autoimmune diseases, manifesting as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondylitis (SpA), can develop following infection with the causative infectious agent of Lyme disease, Borrelia burgdorferi, identified by erythema migrans rash, in spite of the standard short-course antibiotic therapies (some with repeated short-courses) used to treat it. Of 30 patients identified as having new onset autoimmune arthritides within a median timeframe of 4 months post-infection, 15 Lyme patients developed RA, 13 developed PsA (usually preceded by psoriasis), and 2 developed peripheral spondylitis.


Lysosomal β-glucuronidase regulates Lyme and rheumatoid arthritis severity. J Clin Invest. 2014 Jan;124(1):311-20.

University of Utah researchers made a remarkable discovery that they hypothesize may reveal a critical key with regard to how disease severity is regulated in both Lyme disease and Rheumatoid arthritis (RA). On the premise that disease severity among infected patients varies significantly and that host genetics may play a role in disease pathology and outcomes (particularly those who develop arthritis), these researchers took a forward genetics approach to their murine study. In so doing, they identified that a cellular lysomomal enzyme, called glucuronidase (GUSB), was a key component in regulating Lyme-associated arthritis and RA severity. Mice that expressed a certain GUSB transgene, called WT Gusb, were protected from severe Lyme arthritis, whereas mice that expressed a variant of GUSB, called Gusbh, were prone to more severe Lyme arthritis. GUSB’s function is to prevent the lysosomal accumulation of glycosaminoglycans (GAGs) within joint connective tissues and these findings suggest that mice expressing the Gusbh variant had significant accumulation of GAGs in joint tissue. Further, when mice were treated with GUSB, it was found that proinflammatory GAG accumulation within inflamed joint tissue was prevented and arthritis pathogenesis was successfully modulated.


A Painful Inflammatory Lesion on the Dorsum of the Hand of a Patient With Rheumatoid Arthritis Treated With Methotrexate. Clin Infect Dis (2014) 59 (6): 903.

The case of an elderly woman with rheumatoid arthritis, treated with methotrexate, who developed an Acrodermatitis chronica atrophicans (ACA) lesion on the dorsal side of her hand is described. ACA is a known skin manifestation of late stage Lyme disease, occurring months to years after infection, and can resemble morphea scleroderma lesions. Although the patient couldn’t recall a tick bite, she was found positive for Lyme disease and treated with IV ceftriaxone, which resulted in ACA resolution. While ACA can also present with peripheral neuropathy, lymphadenopathy and fibrotic nodules over joints, this complex clinical picture can lead to misdiagnosis. The authors conclude by stating, “…we cannot exclude that long-term methotrexate treatment and the history of axillary lymph node dissection may have induced this late local dissemination.”


The DBA/1 strain is a novel mouse model for experimental Borrelia burgdorferi infection. Clin Vaccine Immunol. 2012 Oct;19(10):1567-73. Epub 2012 Aug 1.

Murine studies at University of Pittsburgh School of Medicine, in Pennsylvania, were conducted to determine which mouse model, based on genetic strains, would make the ideal candidate for studying Lyme arthritis and collagen-induced arthritis in mice, which mirrors rheumatoid arthritis (RA). Collagen-induced arthritis was induced by infecting the different mouse strains with Borrelia burgdorferi, the causative organism of Lyme disease. In their determination of the ideal murine model for further Lyme disease studies, study authors based their findings on the humoral immune response of certain mouse strains and the variation in degree of reactivity to Lyme antigens on testing. Could this finding lend itself to the theory that variations in human genetics might also play a role in human humoral immune response to standard Lyme testing results?


Anti–Tumor Necrosis Factor–a Treatment Activates Borrelia burgdorferi Spirochetes 4 Weeks after Ceftriaxone Treatment in C3H/He Mice. Journal of Infectious Diseases. 195(10):1489-96 · June 2007.

In groundbreaking murine research conducted by the Departments of Medical Microbiology and Medicine at the University of Turku, in Finland, to determine if anti-TNF-alpha medications (used in the treatment of rheumatoid arthritis) would be helpful in Lyme disease, mice were infected with two common strains of Lyme disease. After two weeks of infection, the mice were then divided into 5 groups: one group of mice was treated for 5 days with the antibiotic, ceftriaxone, a second group was treated with anti-TNF-alpha only, a third group was treated with both ceftriaxone and anti-TNF-alpha simultaneously, a fourth group was first treated with ceftriaxone and then anti-TNF-alpha was added (4 weeks after ceftriaxone therapy), and the fifth group was just administered a sham saline treatment. Results of this study demonstrated that mice treated, after 2 weeks of infection, with antibiotics only did not test positive by culture or PCR, but in all mice groups treated with anti-TNF medication, live, actively reproducing spirochetes were found in one-third of the mice. This study revealed that after short-term antibiotic therapy that seronegative Lyme can persist in mice and, further, if immune-suppressive therapy is administered, not only can viable spirochetes still be recovered, but that anti-TNF therapy did not afford reduction in joint swelling.

Further commentary by the Lyme and Tick-borne Research Center at Columbia University Medical Center, NY, can be read here.


[Immunopathology of Lyme arthritis]. Pol Merkur Lekarski. 2007 Aug;23(134):141-4.

Polish researchers conducting histopathological studies of synovia and immunological changes in Lyme arthritis, state that the mechanism that leads to inflamed joints and results in the progressive destruction of articular cartilage and disintegration of extracellular matrix is similar to rheumatoid arthritis. They point to outer surface protein C (OSP C), a specific Lyme antigen, as inducing molecular mimicry of adhesion molecule LFA-1 alpha. This adhesion molecule is found on all human T-cells, B-cells, and neutrophils, and is involved in lymphocytic recruitment of these immune cells to fight infection by binding to ICAM-1 on antigen-presenting cells.


Serum reactivity against Borrelia burgdorferi OspA in patients with rheumatoid arthritis. Clin Vaccine Immunol. 2007 Nov;14(11):1437-41. Epub 2007 Sep 19.

Taiwanese researchers assert that Lyme arthritis and rheumatoid arthritis (RA) share common histopathology and clinical features and the purpose of their study was to determine if the two diseases share similar pathogenesis. Their findings demonstrate that 25% of RA patients (as opposed to 10% of other autoimmune diseases or those with Lyme arthritis) produced serum reactivity against Outer Surface Protein A(OspA) antigen, a highly specific antigenic protein of borrelia burgdorferi, the causative organism of Lyme disease. These researchers conclude that OSP A is associated with the pathogenesis of rheumatoid arthritis.


[Intensity of the production of rheumatoid factor in patients with different degree of sensitization to Borrelia garinii antigens]. Zh Mikrobiol Epidemiol Immunobiol. 2005 Jan-Feb;(1):70-2.

In a Russian study of patients with high titer antibody responses to Borrelia garinii, a pathogenic species of Lyme disease in Eurasia, researchers also found increases in rheumatoid factor titers and discuss the mechanisms of autoimmunity that may follow infection by this organism.


Increased IgA rheumatoid factor and V(H)1 associated cross reactive idiotype expression in patients with Lyme arthritis and neuroborreliosis. Ann Rheum Dis. 1999 Dec;58(12):757-61.

British and American researchers collaborated to investigate whether the autoreactive mechanisms of Lyme disease bore any relationship to IgM, IgG, and IgA concentrations of rheumatoid factor (RF) and RF-associated cross-reactive idiotype (CRI) expression in Lyme disease and rheumatoid arthritis patients. Conclusions drawn by these researchers indicate that in late stage Lyme disease, recruitment of autoreactive B lymphocytes occurred in 18% of patients who exhibited significant elevations of IgA RF.


Pathogenesis of Lyme disease. Rheumatol Int. 1989;9(3-5):233-5. Scand J Rheumatol Suppl. 1988;75:314-7.

A Yale University researcher discusses Lyme disease as a model for infectious causes of rheumatic diseases in consideration of its similarities with rheumatoid arthritis (RA).


IgM rheumatoid factor in Lyme disease: correlation with disease activity, total serum IgM, and IgM antibody to Borrelia burgdorferi. J Rheumatol. 1987 Aug;14(4):772-6.

Researchers in the Department of Internal Medicine, at the University of Virginia School of Medicine, found that 7 out of 25 patients with Lyme arthritis were IgM-Rheumatoid Factor (RF) seropositive and that disease activity correlated with IgM-RF and IgM Borrelia burgdorferi antibody titers.


 

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