Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

Mycosis fungoides: is it a Borrelia burgdorferi-associated disease?

Mycosis fungoides (MF) is the most frequently found cutaneous T-cell lymphoma with an unknown aetiology. Several aetiopathogenetic mechanisms have been postulated, including persistent viral or bacterial infections. We looked for evidence of Borrelia burgdorferi (Bb), the aetiologic agent of Lyme disease (LD), in a case study of MF patients from Northeastern Italy, an area with endemic LD. Polymerase chain reaction for the flagellin gene of Bb was used to study formalin-fixed paraffin-embedded lesional skin biopsies from 83 patients with MF and 83 sex- and age-matched healthy controls with homolocalised cutaneous nevi. Borrelia burgdorferi-specific sequence was detected in 15 out of 83 skin samples of patients with MF (18.1%), but in none out of 83 matched healthy controls (P<0.0001). The Bb positivity rates detected in this study support a possible role for Bb in the aetiopathogenesis of MF in a population endemic for LD

Borrelia Burgdorferi Induces a Type I Interferon Response During Early Stages of Disseminated Infection in Mice

BACKGROUND: Lyme borrelia genotypes differ in their capacity to cause disseminated disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia burgdorferi strains with different capacities for causing disseminated disease in the blood of C3H/HeJ mice during early infection. RESULTS: B. burgdorferi B515, a clinical isolate that causes disseminated infection in mice, differentially regulated 236 transcripts (P \u3c 0.05 by ANOVA, with fold change of at least 2). The 216 significantly induced transcripts included interferon (IFN)-responsive genes and genes involved in immunity and inflammation. In contrast, B. burgdorferi B331, a clinical isolate that causes transient skin infection but does not disseminate in C3H/HeJ mice, stimulated changes in only a few genes (1 induced, 4 repressed). Transcriptional regulation of type I IFN and IFN-related genes was measured by quantitative RT-PCR in mouse skin biopsies collected from the site of infection 24 h after inoculation with B. burgdorferi. The mean values for transcripts of Ifnb, Cxcl10, Gbp1, Ifit1, Ifit3, Irf7, Mx1, and Stat2 were found to be significantly increased in B. burgdorferi strain B515-infected mice relative to the control group. In contrast, transcription of these genes was not significantly changed in response to B. burgdorferi strain B331 or B31-4, a mutant that is unable to disseminate. CONCLUSIONS: These results establish a positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction in a murine model of Lyme disease

The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi

The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity) and PAI-1 (high fibrinolytic activity) knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1β mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system

Is Serological Follow-Up Useful for Patients with Cutaneous Lyme Borreliosis?

Serologic follow-up examinations are frequently performed in patients with erythema migrans, borrelial lymphocytoma, and acrodermatitis chronica atrophicans (the 3 dermatoborrelioses) to evaluate treatment efficacy. There is, however, substantial proof in the literature that antibody titer development after therapy is unpredictable and variable, and moreover it is largely uncorrelated with the clinical course and mode of antibiotic treatment. For example, persistent positive IgG and/ or IgM antibody titers do not indicate treatment failure. Thus, repeated serologic testing is of very limited value for assessing therapy efficacy, and therefore not recommended in the follow-up of dermatoborrelioses patients. Since cultivation of the etiologic agent, Borrelia burgdorferi sensu lato, and polymerase chain reaction are also inadequate for this purpose, the assessment of patients with cutaneous manifestations of Lyme borreliosis in the follow-up rests primarily on the clinical picture

Dermatopathologic diagnosis of Lyme Borreliosis

The goal of this study was to determine the general light microscopic findings which lend support to the histopathologic diagnosis of the main cutaneous manifestations of Lyme Borreliosis. Their diagnostic criteria are delineated and illustrated. In culminating lesions of erythema migrans and acrodermatitis chronica atrophicans, a peculiar connective tissue reaction includes an increase in the number of fibroblasts, proliferation of collagen fibers, and interstitial mucinous edema. The cellular infiltrates are patchy perivascular in erythema migrans and either patchy and/or band-like in acrodermatitis chronica atrophicans. They consist of lymphohistiocytic cells with a variable admixture of plasma cells. The damage to elastic (and even collagen) fibers occurs in early acrodermatitis chronica atrophicans and is reflected by the phenomenon of elastophagocytosis. Reduction or lack of pilosebaceous units is a constant finding. In advanced lesions of acrodermatitis chronica atrophicans, a thinning of the dermal breadth is noticed, resulting from a decrease in collagen and elastic fibers. Fibrous nodules and morphea-like conditions are characterized by excessive formation of collagen. Borrelial lymphocytoma exhibits two different patterns of infiltration, accompanied by dermal fibrosis and increased numbers of fibroblasts. Recent tick bites show a predominantly neutrophilic infiltrate. By applying the results of this synoptic study, histopathologic diagnosis of dermatoborrelioses should be possible without the absolute necessity of clinical correlation

DNA repair enzymes in sunscreens and their impact on photoageing\u2014A systematic review

Background: DNA damage is one of the main factors responsible for photoageing and is predominantly attributed to ultraviolet irradiation (UV-R). Photoprotection by conventional sunscreens is exclusively prophylactic, and of no value, once DNA damage has occurred. As a result, the demand for DNA repair mechanisms inhibiting, reversing or delaying the pathologic events in UV-exposed skin has sparked research on anti-photoageing and strategies to improve the effect of conventional sunscreens. This review provides an overview of recent developments in DNA repair enzymes used in sunscreens and their impact on photoageing. Methods: A systematic review of the literature, up to March 2019, was conducted using the electronic databases, PubMed and Web of Science. Quality assessment was carried out using the Newcastle-Ottawa scale (NOS) to ensure inclusion of adequate quality studies only (NOS\ua0>\ua05). Results: Out of the 352 publications, 52 were considered relevant to the key question and included in the present review. Two major enzymes were found to play a major role in DNA damage repair in sunscreens: photolyase and T4 endonuclease V. These enzymes are capable of identifying and removing UV-R-induced dimeric photoproducts. Clinical studies revealed that sunscreens with liposome-encapsulated types of photolyase and/or T4 endonuclease V can enhance these repair mechanisms. Conclusion: There is a lack of randomized controlled trials demonstrating the efficacy of DNA repair enzymes on photoageing, or a superiority of sunscreens with DNA repair enzymes compared to conventional sunscreens. Further studies are mandatory to further reveal pathogenic factors of photoageing and possible therapeutic strategies against it

Erythema migrans multiloculare in Styria (Austria)

To characterize clinical, serologic, and histopathologic features of patients with erythema migrans multiloculare from Styria (Austria), an European area well known to be endemic for Lyme Borreliosis, 270 consecutive patients (m:f = 128:142, mean age = 54 years) with erythema migrans were studied at the Department of Dermatology in Graz, Austria between March 1993 and October 1995. 17/270 patients (m:f = 9:8, mean age = 37 years) (6.3%) presented with a multifocal form of the disease. Several findings in these 17 patients were remarkable. Anamnestic data/clinical findings: History of tick or insect bite(s): 10/17 patients (4 singular, 6 multiple); mean total number of lesions/patient = 4 (ranging 2-18); latency of 1-14 days (mean 7 days) in 9/17 patients (53%) between primary erythema migrans and secondary lesions; in these 9 patients the secondary lesions showed a different morphologic aspect in comparison to the primary erythema migrans; extracutaneous signs and symptoms: 7/17 patients (41%). Serologic findings: Borrelia burgdorferi serum ELISA IgG-antibodies: 9/17 patients (53%), IgM: 9/17 patients (53%). Histopathologic findings: Complete lack of epidermal changes and milder inflammatory dermal infiltrate in all secondary lesions (4 biopsy specimens) in comparison to primary erythemata migrantia (5 biopsy specimens). Our clinical and serologic findings are largely in accordance with the scarce literature on this condition from Europe where erythema migrans multiloculare is much rarer than in the USA. The pathogenesis of erythema migrans multiloculare which is currently defined to be a disseminated form of Lyme Borreliosis due to haematogenous spread of Borrelia burgdorferi will be discussed in consideration of our observations