© Borgis - New Medicine 4/2010, s. 152-155
*Małgorzata Tokarska-Rodak1, Justyna Niedźwiadek1, Hanna Fota-Markowska2, Filip Śmiechowicz2, Bożena Gajownik3, Roma Modrzewska2, Maria Kozioł-Montewka1
Antinuclear antibodies in patients with Lyme disease
1Department of Medical Microbiology, Medical University, Lublin, Poland
Head of Department of Medical Microbiology: prof. dr hab. Maria Kozioł-Montewka
2Department of Infectious Diseases, Medical University, Lublin, Poland
Head of Department of Infectious Diseases: prof. dr hab. n. med. Roma Modrzewska
3Clinic of Infectious Diseases, Public Hospital in Łuków, Poland
Head of Clinic of Infectious Diseases: Bożena Gajownik
Aim. The aim of the study was to determine the relation between B. burgdorferi infection in patients with clinical symptoms of Lyme disease and presence of antinuclear antibodies (ANA) depending on the duration of the disease and in the aspect of the erythema migrans (EM) experience.
Material and methods. The study was conducted in a group of 110 patients with the second stage of Lyme disease hospitalized during 2007-2009. The ANA were determined by the IIFT test and the Western blot test.
Results. Positive ANA results (IIFT test) were obtained for 16 patients. The presence of ANA (Western blot test) was confirmed in 4 women who reported a single bite by ticks before 2000, EM presence in the past and the administration of antibiotic treatment due to Lyme disease because of EM and ailments concerning bone-joint structure but without the presence of autoimmune diseases.
Conclusions. The relation between primary diagnosis of Lyme disease in the form of EM and occurrence in the late period is possible despite the application of treatment of joint symptoms with simultaneous presence of ANA antibodies.
The primary cause of Lyme disease is always infection with spirochetes of B. burgdorferi s.l. However, the clinical course of the disease is to some extent dependent on the bacteria gene-species, their number and effectiveness of the immune system of the infected person. B. burgdorferi can survive through unfavourable periods and avoid the attack from the immunological system of a host by using the strategy of creating atypical forms
(1, 2). In the specific conditions of an environmental stress, the spirochetes can undergo reversible transformation from the motile helical forms into non-motile spherical cysts. These forms have been observed in the cerebrospinal fluid and in tissues of patients with Lyme disease (3). The metabolically inactive forms ?blebs?, which contain genetic material of B. burgdorferi, are also a source of long-term antigenic stimulation. It is possible that the presence of atypical forms is also a cause of converted symptoms of the disease and the necessity of repeating the antibiotic therapy (4, 5, 6).
In spite of the enormous knowledge concerning the clinical process of B. burgdorferi infection and the development of therapeutic schemas, it is difficult to unambiguously determine the mutual host-pathogen relations which determine the effective and complete elimination of the spirochetes.
Despite the application of antibiotic therapy in the erythema migrans phase, the transition of Lyme disease into disseminated and late stage is infrequently avoided (7, 8, 9, 10). The cognition and comprehension of those numerous relations and mechanisms of their formation can have an influence on the improvement of applied methods, prevention and effective treatment of B. burgdorferi infection.
Aim of the study
The aim of the study was to determine the relation between B. burgdorferi infection in patients with clinical symptoms of Lyme disease and presence of antinuclear antibodies depending on the duration of the disease and in the aspect of the erythema migrans (EM) experience.
Material and methods
The study was conducted in a group of 110 patients: 44 men (age 20-66 yrs) and 66 women (age 20-60 yrs) with the second stage of Lyme disease, hospitalized in the Clinic of Infectious Diseases, Medical University of Lublin, and the Department of Infectious Diseases, Hospital in Łuków, in 2007-2009. The study group involved patients demonstrating manifestations of joint involvement including arthralgia and/or arthritis. The diagnosis of borreliosis was established on the basis of the patient?s medical history, physical examination, clinical picture, and serological investigation (ELISA and Western blot).
All patients were asked to respond to a questionnaire to gather information about the dates and frequency of tick bites, incidents of EM, symptoms that occurred following the tick bite and antibiotics taken.
The antinuclear antibodies were determined by the IIFT test among all of the examined patients (Biomedical Diagnostics). In the patients where a titre of 1:200 or more was obtained, the Western blot test (Euroimmun) was carried out on the quality indication in vitro with human IgG antibodies against 15 antigens: nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, PM-Scl, Jo-1, CENP B, PCNA, dsDNA, nucleosomes, histones, ribosome protein P and AMA-M2.
The patients examined in 2007-2009 due to Lyme disease with dominant joint symptoms reported in the completed survey about the time (year) of being bitten by ticks, the multiple of a bite and the application of antibiotic therapy in the past due to clinical symptoms appearing after tick bites (fig. 1).
Fig. 1. Year of the tick bites reported by patients with clinical symptoms of Lyme disease and patients with positive result of ANA test.
*positive result of ANA test (IIFT)
**positive result of ANA test (Wb)
The early stage of located Lyme disease (EM) appeared among 65 from 110 examined patients (59%) in the past and for that reason 43 patients from this group (66%) underwent antibiotic treatment. Twenty-two patients (34%) in spite of the presence of EM did not undergo treatment. Among all of these patients, regardless of the treatment?s application or the lack of it, the clinical symptoms of the second stage of Lyme disease were developed.
EM did not appear in 45 patients (41%), while the symptoms of early disseminated Lyme disease appeared among all of the patients from this group. Lyme disease was diagnosed among subsequent 22 patients (49%) in 2007-2009 (i.e. during the present research).
All of the examined patients reported simultaneous appearance of various clinical ailments with Lyme disease. Ailments concerning bone-joint structure were noted frequently by 105 patients (95%), among which 12 cases concerned arthritis (13%).
Sixty patients (54%) reported muscle pains, 29 (26%) reported headaches, and 24 (22%) reported concentration disorder. Among 110 patients, 21 (19%) reported the presence of other symptoms such as meningitis, sensory loss, stiffening and oedema of the lower limbs, skin changes different from EM, fever, tinnitus and impaired sharpness of vision.
The determination of the ANA was implemented by the IIFT method in 110 patients with Lyme disease (fig. 2). Positive results of the test were obtained in 16 patients. The titre of 1:200 or more was accepted as a positive result. Cytoplasmic fluorescence was observed among
12 cases, with 4 different types of fluorescence: mitochondrial, granular nucleus, homogeneous nucleus.
Fig. 2. Medical history findings in 16 patients with Lyme arthritis and positive result of ANA tests.
*single tick bite, **double tick bite, EM ? presence of EM, O treatment, ? no treatment
In the patients with a positive result of the IIFT test, the Western blot test was carried out on the quality indication in vitro with human IgG antibodies against 15 antigens: nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, PM-Scl, Jo-1, CENP B, PCNA, dsDNA, nucleosomes, histones, ribosome protein P and AMA-M2.
The following results were obtained:
? 1 patient (mitochondrial type of fluorescence) ? IgG anti-AMA-M2, Ro 52, SSB,
? 1 patient (type of fluorescence granular nucleus)
? IgG anti-CENP B
? 1 patient (type of fluorescence granular nucleus)
? IgG anti-SSA
? 1 patient (type of fluorescence homogeneous nucleus) ? IgG anti-nucleosomes.
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