The interferon-induced helicase C domain-containing protein 1 gene variant (rs1990760) as an autoimmune-based pathology susceptibility factor.

PURPOSE: Autoimmune diseases are a group of complex diseases localized in multiple organ systems, with a wide spectrum of symptoms and still unclear causes. The aim of the present study was to analyse a possible association of three autoimmune disabilities - Multiple sclerosis (MS), LADA diabetes and Graves' disease (GD) with single nucleotide polymorphism (SNP; rs1990760) in the IF IH1 gene (also known as a melanoma differentiation-associated protein 5 - MDA5) within the Polish population. An additional goal was also to look for a correlation between this polymorphism and different clinical patient-related factors. MATERIALS AND METHODS: The study population consisted of four groups of 944 unrelated Polish origin Caucasian patients - 324 with GD, 171 with MS, 49 with LADA diabetes and 400 healthy subjects as a control group. The SNP analysis was performed using the allelic discrimination technique. RESULTS & CONCLUSIONS: There were significant associations of risk T allel of the analyzed polymorphism with all studied autoimmune diseases (GDOR = 1.34, p = 7.02e-03; MSOR = 1.36, p = 2.17e-02; LADA - OR = 3.36, p = 8.73e-07). We also found that the frequency of CT and TT genotypes of the rs1990760 IFIH1 gene only in females (with LADA, GD, MS) was significantly higher than those in the female control group (47%, 41% vs 44%, 34%; p = 1.32e-03, p = 4.39e-04; OR = 2.08, 95%CI: (1.33-3.28), OR = 2.29, 95% CI: (1.44-3.65) respectively). Our research has shown significant differences regarding some clinical features (BMI, TRAb, TSH, HbA1C, anti-GAD antibodies) and age at the beginning of the studied autoimmune disabilities. This study showed an association of rs1990760 polymorphism in the IFIH1 gene in the development of GD, LADA diabetes and MS within the Polish population. To our knowledge, this is the first study to investigate the relationship between IFIH1 polymorphisms and the risk of the development of MS and LADA in Poland.

Analysis of chosen SNVs in GPC5, CD58 and IRF8 genes in multiple sclerosis patients.

PURPOSE: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system with a neurodegenerative compound. Heterogenetic background of autoimmunity pathway components has been suggested in the MS pathogenesis. The main aim of our study was to evaluate the association between selected polymorphisms of theCD58, IRF8 and GPC5 genes and treatment effectiveness in a group of relapsing-remitting MS patients. This is the first study of MS patients from Podlaskie Region in the Polish population. MATERIALS AND METHODS: The study group comprised 174 relapsing-remitting MS patients diagnosed under 40 years of age. Genotyping was performed using ready to use TaqMan assays. RESULTS: We demonstrate a strong association of the polymorphisms with sex, age of onset and response to the treatment applied. A significant correlation was observed in the presence of allele T of rs10492503 polymorphism inGPC5 gene with sex and age of MS onset. Logistic regression analysis revealed an increased risk of the interaction of rs17445836 in IRF8 gene with male sex and the type of treatment (OR = 3.80, p < 0.05), and a decreased risk in the interaction of female sex with disease progress according to the EDSS scale (OR=-2.33, p < 0.05). CONCLUSIONS: The analysis of the correlation between different alleles, genotypes and clinical status confirmed the interaction between the genetic factors of age of onset and response to therapy. The study suggests that genetic variants inGPC5, CD58 and IRF8 genes may be of clinical interest in MS as predictors of age of onset and response to therapy.

Post-mortem detection of six human herpesviruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6) in trigeminal and facial nerve ganglia by PCR.

BACKGROUND: Among over 100 types of Herpesviridae viruses, eight can infect humans: herpes simplex viruses (HSV-1, HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesviruses 6, 7, and 8 (HHV-6, HHV-7, HHV-8). After initial infection, the viruses remain latent for the lifetime of the host. The aim of this study was to determine the distribution of six different herpesviruses: HSV-1, HSV-2, VZV, EBV, CMV, and HHV-6 in trigeminal and facial nerve ganglia among a random group of Polish population. METHODS: The studied group consisted of 47 individuals (40 male, seven female); mean age of 47.4 ± 16.5 years) who died of independent causes (suicide, traffic accident, and poisoning, among others). Bilateral trigeminal and facial nerve ganglia of each cadaver were collected during the autopsy. Herpesviruses were detected using multiplex polymerase chain reaction technique. RESULTS: Herpesviruses were found in trigeminal and/or facial ganglia in 30/47 (63.8%) of cadavers. HHV-6 was the most prevalent of the herpesviruses and was found in nearly half of cadavers (n = 22; 46.8%), followed by HSV-1 (n = 7; 14.9%), VZV (n = 4; 8.5%), EBV (n = 4; 8.5%), HSV-2 (n = 2; 4.3%), and CMV (n = 1; 2.1%). Facial nerve ganglia (n = 23; 48.9%) were more often infected than trigeminal ganglia (n = 13; 27.7%). DISCUSSION: The results of this study have revealed a common presence of the herpesviruses in trigeminal and facial nerve ganglia among a random group of Polish population. Furthermore, the data also demonstrate simultaneous infection of the ganglia with different herpesviruses. This study has contributed to the knowledge of prevalence and localization of herpesviruses in different structures of the nervous system.

The FOXP3 rs3761547 Gene Polymorphism in Multiple Sclerosis as a Male-Specific Risk Factor.

The FOXP3 gene encodes a transcription factor and is predominantly expressed in the CD4+CD25+ regulatory T cells which plays a pivotal role in the maintenance of immune homeostasis. The defect of FOXP3 gene may provide a critical link between autoimmunity and immune deficiency. The purpose of our study was to evaluate the association of chosen polymorphisms of FOXP3 gene (rs3761549, rs3761548, rs3761547) with different clinical multiple sclerosis (MS) data of our relapsing-remitting groups of patients and in control group. The study was performed on a group consisting of 174 relapsing-remitting MS patients, diagnosed under 40 years of life, and 174 healthy volunteers. Genotyping was performed using a real-time PCR-based method by TaqMan Assays. Significant differences in distribution of allele C rs3761547 were found in male MS patients in comparison to the male healthy group (p = 0.046, OR 1.95, CI 95%). No association between MS and the other two polymorphisms was observed in males and females of both studied groups. Our data may suggest that FOXP3 rs3761547 gene polymorphism are related notably with the increased risk of MS development in males patients. To our knowledge this is the first study which indicates gender-specific relation between rs3761547 FOXP3 gene polymorphism and multiple sclerosis.

Cerebrovascular Manifestations of Lyme Neuroborreliosis-A Systematic Review of Published Cases.

BACKGROUND: Lyme neuroborreliosis (LNB) is a disease caused by spirochete Borrelia burgdorferi, involving the nervous system. It usually manifests as lymphocytic meningoradiculitis, but in rare cases, it can also lead to cerebrovascular complications. We aimed to perform a systematic review of all reported cases of LNB complicated by central nervous system vasculitis and stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: We conducted a systematic review of literature between May 1987 and December 2016 with patients who presented with cerebrovascular course of LNB. RESULTS: This study included 88 patients with a median age of 46 years. The median interval from onset of symptoms suggesting Lyme disease to first symptoms of cerebrovascular manifestations of LNB was 3.5 months. The most common cerebrovascular manifestation of LNB was ischemic stroke (76.1%), followed by TIA (11.4%). The posterior circulation was affected alone in 37.8% of patients, the anterior circulation in 24.4% of patients, and in 37.8% of cases, posterior and anterior circulations were affected simultaneously. The most common affected vessels were middle cerebral artery-in 19 cases, basilar artery-in 17 cases, and anterior cerebral artery-in 16 cases. A good response to antibiotic treatment was achieved in the vast number of patients (75.3%). The overall mortality rate was 4.7%. CONCLUSION: Cerebral vasculitis and stroke due to LNB should be considered, especially in patients who live in or have come from areas with high prevalence of tick-borne diseases, as well as in those without cardiovascular risk factors, but with stroke-like symptoms of unknown cause.

Evaluation of Chosen Cytokine Levels among Patients with Herpes Zoster as Ability to Provide Immune Response.

AIM AND BACKGROUND: Herpes zoster is a viral disease caused by the reactivation of varicella-zoster virus (VZV) which remained latent in the cranial nerve or dorsal root ganglia. Cell-mediated immunity is known to decline with age as part of immunosenescence and can lead to the reactivation of VZV. Whereas herpes zoster is usually mild in healthy young persons, older patients are at increased risk for complications. In the present study we investigated the serum cytokine profile (IL-17, IL-23, IL-21, IL-4, IL-12), representing cellular and humoral immunity and assessed the level of VZV IgG antibodies in patients with herpes zoster. METHODS: We investigated the serum concentrations of IL-17, IL-23, IL-21, IL-4, IL-12 and the level of VZV IgG antibodies in 23 patients with herpes zoster who did not develop superinfection. The control group was represented by 21 individuals in similar age with no inflammatory and infectious diseases. Cytokine and antibodies levels were measured by ELISA method. Statistical analysis was performed using the ROC curve (receiver operating characteristic), t-test, Welch's t-test, and nonparametric tests with STATISTICA 10 software. RESULTS: In patients with herpes zoster, the serum level of IL-17, IL-23, IL-21, IL-4 and IL-12 as well as VZV IgG antibodies titer were statistically significantly increased compared to control group. CONCLUSION: Our results confirm the broad activation of the immune system involving humoral and cell-mediated immunity.

Seroprevalence of parvovirus B19 antibodies among young pregnant women or planning pregnancy, tested for toxoplasmosis.

INTRODUCTION AND OBJECTIVE: Acute parvovirus B19 (B19V) infection is a proven risk for pregnant women and fetus. The aim of this study was to determine the prevalence of B19V antibodies among pregnant women or planning pregnancy, who were referred for preventive toxoplasmosis screening. MATERIAL AND METHODS: Between 2007-2010, 55 women in the age between 21 and 40 years were tested for both B19V IgG and IgM antibodies and sociodemographic information was collected. RESULTS: Among the study group, the mean age was 30 years, 43.6% of women were positive only for B19V IgG antibodies, 9% were positive for both B19V IgG and IgM antibodies and 11% were positive only for B19V IgM antibodies. Women negative for B19 IgG antibodies (47.3%) were considered as a high-risk group of B19V viremia. The serological profile indicating infection with Toxoplasma gondii was considered as a risk factor for fetal distress. The T. gondii IgG antibodies were detected in 51% cases, in 32.7% antibodies were positive for both IgG and IgM, while in 16.3% cases both IgG and IgM were negative. CONCLUSIONS: B19V infection and overlapping of other independent risk factors during pregnancy pose a significant hazard to fetus during development. Therefore, we recommend further broadening the epidemiological database of B19V infection prevalence among women. B19V infection should be taken into account during differential diagnosis as a cause of miscarriage.

Meningitis, clinical presentation of tetanus.

Background. Tetanus is an acute disease caused by a neurotoxin produced by Clostridium tetani. Tetanus immunization has been available since the late 1930s but sporadic cases still occur, usually in incompletely vaccinated or unvaccinated individuals. Case Report. An elderly previously vaccinated female contracted tetanus following foot injury. Clinically she presented with meningitis causing diagnostic and therapeutic delays. Why Should Physician Be Aware of This? Even in developed countries the differential diagnosis of meningitis, especially in the elderly, should include tetanus. Treatment in intensive care unit is required. General population might benefit from vaccine boosters and education on this potentially fatal disease.

Blindness resulting from orbital complications of ophthalmic zoster.

Herpes zoster ophthalmicus occurs when the latent varicella zoster virus (VZV) reactivates in the trigeminal ganglion and ophthalmic branch of the trigeminal nerve. In the elderly, there is a sharp increase in the tendency of secondary skin bacterial infections occurrence due to the deterioration of capabilities of self-care and changed sanitation. We present a case of patient who developed phlegmon of the orbit, which resulted with complete unilateral blindness. Varicella zoster virus infection in the elderly may have a severe course due to the progressive weakening of the immune system related to the age. Moreover, skin lesions around the eye socket require special care in prevention of bacterial superinfections due to the extremely high risk of life-threatening complications or disability. Neuralgia resistant to pharmacological treatment present in the course of ophthalmic zoster and difficulty in caring about skin lesions predispose to the occurrence of complications.

Evaluation of visinin-like protein 1 concentrations in the cerebrospinal fluid of patients with mild cognitive impairment as a dynamic biomarker of Alzheimer's disease.

BACKGROUND: The correlations between pathology of neurodegenerative diseases, especially Alzheimer's disease (AD), and concentrations of neuronal calcium sensor proteins, such as visinin-like protein 1 (VILIP-1), in cerebrospinal fluid (CSF) have been discussed in the literature but its utility as biomarker of AD in comparison with mild cognitive impairment (MCI) has not been studied yet. OBJECTIVE: Therefore, the aim of our study was to assess the clinical utility of the measurement of CSF concentrations of VILIP-1 in patients with AD, MCI subjects, and non-demented controls. The clinical and neuropsychological diagnoses were supported by CSF biomarkers of neurochemical dementia diagnostics: decreased concentrations of Aß1-42 and/or Aß42/40 ratio and increased concentrations of Tau and pTau181 proteins. METHODS: The study included 33 AD patients, 15 subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF concentrations of biomarkers tested were determined by using the ELISA method. RESULTS: Concentrations of VILIP-1 in CSF were significantly higher in AD patients compared to the MCI subjects and elderly individuals without cognitive impairment. Increased concentrations of VILIP-1 correlated significantly with reduced Aß42/40 ratio and higher pTau181 in AD group. CONCLUSION: Our findings suggest that VILIP-1 may play a role in the AD pathophysiology and is a good candidate for dynamic biomarker of AD, although this issue requires further investigation.

Listerial rhombencephalitis in an immunocompetent woman.

Listeriosis usually affects immunocompromised patients including elderly people and pregnant women, but it may also affect otherwise healthy individuals. In our report, we present a case of a rare and very severe form of listeriosis-rhombencephalitis in a 61-year-old female with no history of immunosuppression, who, because of history, clinical picture, and laboratory results as well as negative cultures, was at first diagnosed with viral encephalitis. This paper underlines that Listeria monocytogenes infection should be taken into consideration in case of lymphocytic encephalitis even in immunocompetent patients. Typical MRI picture may be crucial in establishing a proper diagnosis as the lab results may be misleading.

Infectious spondylodiscitis - a case series analysis.

PURPOSE: We aimed to describe the clinical and laboratory features as well as diagnostic difficulties in the case series of spondylodiscitis. MATERIALS/METHODS: We retrospectively reviewed 11 cases of spondylodiscitis. The diagnosis of spondylodiscitis was based on clinical, radiological and microbiological evidence and by the response to antimicrobial therapy. RESULTS: There were 7 men and 4 women, and the age ranged from 21 to 74 years. Risk factors of spondylodiscitis were observed in 7 patients. The approximate time from onset of symptoms to diagnosis was from 2 to 7 months (median 45 days). Back pain was the most common symptom. The most frequent location of spondylodiscitis was lumbar spine. Pathogens were isolated in 6 cases and were as follows: Staphylococcus aureus (4 cases), Staphylococcus warneri (1 case) and Escherichia coli (1 case). After therapy, all patients had rapid regression of symptoms and no permanent neurological impairments and recurrence of infection were observed. CONCLUSIONS: Diagnosis of spondylodiscitis is frequently delayed. This disease should be taken into consideration in differential diagnosis in patients with root syndromes accompanied by back pain and usually fever as well as increased values of CRP and ESR.

Vipera berus bites in Eastern Poland--a retrospective analysis of 15 case studies.

INTRODUCTION AND OBJECTIVE: The common European adder (Vipera berus) is the only venomous snake that is found naturally in Poland. This study presents the epidemiological and clinical characteristics of V.berus bites in Eastern Poland and describes the methods of poisoning treatment. MATERIALS AND METHODS: Medical documentation of 15 patients hospitalized at the Department of Infectious Diseases and Neuroinfections of the Medical University of Bialystok between 1998-2010 because of V.berus bite was analyzed retrospectively. RESULTS: Most of the snakebites were accidental (86.7% of the cases). The bites usually took place in forests (66.7% of the cases). The majority of patients were bitten in the lower extremity (8 cases, 53.3%), most often in the area of ankle joint. The severity of poisoning was usually minor to moderate. The most common local symptom was oedema (93.3% of the cases) and associated extravasations (73.3% of the cases). One patient experienced shock. Transient hypertension was observed in 3 cases. Mild coagulation disorders were present in 4 cases. In 4 cases, leukocytosis was observed. 86.7% of patients received the specific antivenom. No fatal outcome and no adverse reactions after antivenom administration were reported. CONCLUSIONS: In the majority cases of poisoning with V.berus venom, the poisoning takes a mild course, limited to local oedema, but sometimes it may lead to severe complications. The only specific method of the treatment is antivenom administration.