Browsing by Author "Grāvelsiņa, Sabīne"

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    Association of Baseline Lipopolysaccharide-Binding Protein with Expanded Disability Status Score Dynamics in Patients with Relapsing–Remitting Multiple Sclerosis : A Pilot Study
    (2025-01) Vilmane, Anda; Koļesova, Oksana; Nora-Krūkle, Zaiga; Koļesovs, Aleksandrs; Pastare, Daina; Jaunozoliņa, Līga; Kande, Linda; Egle, Jeļena; Kromane, Daniela; Mičule, Madara; Liepiņa, Sintija; Zeltiņa, Estere; Grāvelsiņa, Sabīne; Rasa-Dzelzkalēja, Santa; Vīksna, Ludmila; Karelis, Guntis; Institute of Microbiology and Virology; Department of Infectology; Department of Neurology and Neurosurgery; Department of Radiology
    Forecasting the progression of the disease in the early inflammatory stage of the most prevalent type of multiple sclerosis (MS), referred to as relapsing–remitting multiple sclerosis (RRMS), is essential for making prompt treatment modifications, aimed to reduce clinical relapses and disability. In total, 58 patients with RRMS, having an Expanded Disability Status Scale (EDSS) score less than 4, were included in this study. Baseline magnetic resonance imaging (MRI) was performed, and brain and spinal cord lesions were evaluated. The disability of the patients was evaluated using EDSS at baseline and follow-up; enzyme-linked immunosorbent assays (ELISAs) were also used to determine the level of blood-based inflammation markers in plasma at baseline. The main results demonstrated that the baseline level of LBP was correlated with an increase in EDSS in a short (8–10 months) follow-up period. Furthermore, the prognostic significance of LBP was only observed in patients who received disease-modifying treatment (DMT) before the study. Our results suggest that the baseline level of LBP may be among the predictors of disability progression in RRMS over short follow-up periods, particularly in those receiving treatment. It highlights the effect of endotoxins in the pathogenesis of RRMS.
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    Biomarkers in the diagnostic algorithm of myalgic encephalomyelitis/chronic fatigue syndrome
    (2022-10-10) Grāvelsiņa, Sabīne; Vilmane, Anda; Svirskis, Simons; Rasa-Dzelzkaleja, Santa; Nora-Krūkle, Zaiga; Vecvagare, Katrine; Krumina, Angelika; Leineman, Iana; Shoenfeld, Yehuda; Murovska, Modra; Institute of Microbiology and Virology; Department of Infectology
    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that is mainly diagnosed based on its clinical symptoms. Biomarkers that could facilitate the diagnosis of ME/CFS are not yet available; therefore, reliable and clinically useful disease indicators are of high importance. The aim of this work was to analyze the association between ME/CFS clinical course severity, presence of HHV-6A/B infection markers, and plasma levels of autoantibodies against adrenergic and muscarinic acetylcholine receptors. A total of 134 patients with ME/CFS and 33 healthy controls were analyzed for the presence of HHV-6A/B using PCRs, and antibodies against beta2-adrenergic receptors (β2AdR) and muscarinic acetylcholine receptors (M3 AChR and M4 AChR) using ELISAs. HHV-6A/B U3 genomic sequence in whole-blood DNA was detected in 19/31 patients with severe ME/CFS, in 18/73 moderate ME/CFS cases, and in 7/30 mild ME/CFS cases. Severity-related differences were found among those with a virus load of more than 1,000 copies/106 PBMCs. Although no disease severity-related differences in anti-β2AdR levels were observed in ME/CFS patients, the median concentration of these antibodies in plasma samples of ME/CFS patients was 1.4 ng/ml, while in healthy controls, it was 0.81 ng/ml, with a statistically significant increased level in those with ME/CFS (p = 0.0103). A significant difference of antibodies against M4 AChR median concentration was found between ME/CFS patients (8.15 ng/ml) and healthy controls (6.45 ng/ml) (p = 0.0250). The levels of anti-M4 plotted against disease severity did not show any difference; however, increased viral load correlates with the increase in anti-M4 level. ME/CFS patients with high HHV-6 load have a more severe course of the disease, thus confirming that the severity of the disease depends on the viral load—the course of the disease is more severe with a higher viral load. An increase in anti-M4 AchR and anti-β2AdR levels is detected in all ME/CFS patient groups in comparison to the control group not depending on ME/CFS clinical course severity. However, the increase in HHV-6 load correlates with the increase in anti-M4 level, and the increase in anti-M4 level, in turn, is associated with the increase in anti-β2AdR level. Elevated levels of antibodies against β2AdR and M4 receptors in ME/CFS patients support their usage as clinical biomarkers in the diagnostic algorithm of ME/CFS.
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    Does the course of disease influence the development of fatigue in rheumatoid arthritis patients?
    (2021-04-01) Kadiša, Anda; Nora-Krūkle, Zaiga; Sokolovska, Lība; Grāvelsiņa, Sabīne; Vecvagare, Katrīne; Svirskis, Šimons; Lejnieks, Aivars; Murovska, Modra; Department of Internal Diseases; Institute of Microbiology and Virology
    Patients with rheumatoid arthritis (RA) typically have many permanently inflamed joints. The inflammation inside the body can lead to general physical weakness, exhaustion, and drowsiness. This feeling of extreme tiredness is also called “fatigue”. Some people find this to be the worst symptom of the disease. However, the clinical significance of fatigue and its pathogenesis have not been recognised. This study aimed to determine the development of fatigue depending on activity and aggressiveness of RA. To achieve the goal, patients were interviewed and indicators of disease activity and aggressiveness were determined: rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulins IgA RF, IgM RF, IgG RF and anti-carbamylated protein antibodies (anti-CarP). Based on the results of the survey, RA patients were divided into two groups - with and without fatigue. In the group of RA patients with fatigue, statistically more often an increase in IgA RF, IgM RF, and IgG RF levels was observed in those with elevated RF level, higher IgM RF and IgG RF levels were associated with increase in IgA RF level, and increase in the IgG RF and anti-CarP levels with elevation in the IgM RF level. A higher IgG RF level contributed to a higher anti-CarP level increase. Significant differences in the levels of clinical and laboratory inflammatory markers were not observed between the RA patients with and without fatigue. The obtained data suggest that the aggressive course of RA, more than inflammation, may contribute to the development of fatigue in RA patients.
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    Exploring the Joint Potential of Inflammation, Immunity, and Receptor-Based Biomarkers for Evaluating ME/CFS Progression
    (2023-12-20) Berķis, Uldis; Svirskis, Šimons; Krūmiņa, Angelika; Grāvelsiņa, Sabīne; Vilmane, Anda; Arāja, Diāna; Nora-Krūkle, Zaiga; Murovska, Modra; Development and Project Department; Institute of Microbiology and Virology; Department of Infectology
    Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition with no identified diagnostic biomarkers to date. Its prevalence is as high as 0.89% according to metastudies, with a quarter of patients bed- or home-bound, which presents a serious public health challenge. Investigations into the inflammation-immunity axis is encouraged by links to outbreaks and disease waves. Recently, research of our group revealed that antibodies to beta2-adrenergic (anti-β2AdR) and muscarinic acetylcholine (anti-M4) receptors demonstrate sensitivity to the progression of ME/CFS. The purpose of this study is to investigate the joint potential of inflammatome - characterized by interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-21, Il-23, IL-6, IL-17A, Activin-B, immunome (IgG1, IgG2, IgG3, IgG4, IgM, IgA) and receptor-based biomarkers (anti-M3, anti-M4, anti-β2AdR) determined -, for evaluating ME/CFS progression, and to identify an optimal selection for future validation in prospective clinical studies. Methods: A dataset was used originating from 188 persons, including 54 healthy controls, 30 patients classified as "mild" by severity, 73 as "moderate," and 31 as "severe," clinically assessed by Fukuda/CDC 1994 and International consensus criteria. Markers characterizing inflammatome, immunome, and receptor-based biomarkers were determined in blood plasma via ELISA and multiplex methods. Statistical analysis was done via correlation analysis, principal component, and linear discriminant analysis, and random forest classification; inter-group differences tested via nonparametric Kruskal–Wallis H test followed by the two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli, and via Mann-Whitney U test. Results: The association between inflammatome and immunome markers is broader and stronger (coupling) in severe group. Principal component factoring separate components affiliated with inflammatome, immunome, and receptor biomarkers. Random forest modeling demonstrates an out-of-box accuracy for splitting healthy/with condition groups of over 90%, and of 45% for healthy/severity groups. Classifiers with the highest potential are anti-β2AdR, anti-M4, IgG4, IL-2, and IL-6. Discussion: Association between inflammatome and immunome markers is a candidate for controlled clinical study of ME/CFS progression markers that could be used for treatment individualization. Thus, coupling effects between inflammation and immunity have a potential for the identification of prognostic factors in the context of ME/CFS progression mechanism studies.
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    Presence of Human Bocavirus 1 in Hospitalised Children with Acute Respiratory Tract Infections in Latvia and Lithuania
    (2016-08-01) Nora-Krūkle, Zaiga; Rasa, Santa; Vilmane, Anda; Grāvelsiņa, Sabīne; Kālis, Mārtiņš; Ziemele, Inga; Naciute, Milda; Petraitiene, Sigita; Mieliauskaite, Diana; Klimantaviciene, Migle; Girkontaite, Irute; Liu, Hsin Fu; Lin, Jih Hui; Lin, Yung Cheng; Chan, Hsiu Chuan; Gardovska, Dace; Murovska, Modra; Institute of Microbiology and Virology; Rīga Stradiņš University
    Human bocavirus 1 (HBoV1) is a parvovirus recently found to be a possible aetiologic agent of acute respiratory disease in children. We conducted the first clinical and molecular study on this virus in Latvia (LV) and Lithuania (LT). The aim of the study was to determine the occurrence of HBoV1 in respiratory tract samples taken from hospitalised children with acute respiratory tract infections in LV and LT. In total 186 children with age one to 50 months, and who fulfilled criteria of acute respiratory tract infection, including lower respiratory tract infections, with or without fever, were included in this study. A nasopharyngeal aspirate was obtained from each patient on admission. DNA was isolated and polimerase chain reaction (PCR) performed targeting the HBoV1 NS1sequence. HBoV1 positive samples were sequenced and phylogenetic analysis was performed. HBoV1 sequence was detected in 42 (32%) of 130 LV and in 8 (14%) of 56 LT samples. In LV the majority of patients with HBoV1 infection were observed in February while in LT in October. The phylogenetic tree for HBoV1 indicated that isolates of HBoV1 cluster closely and include almost all of the isolates in this study. HBoV1 is common in Latvia and Lithuania and might be a significant pathogen that contributes to acute respiratory tract infections in children.
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    Prevalence of KIR2DL2/DS2 and KIR2DL3 and presence of B19V in patients with thyroid disorders
    (2021-02-01) Grāvelsiņa, Sabīne; Caselli, Elisabetta; Nora-Krūkle, Zaiga; Svirskis, Simons; Vilmane, Anda; Di Luca, Dario; Murovska, Modra; Institute of Microbiology and Virology
    The functions of human natural killer cells are controlled by diverse families of antigen receptors. Prominent among these are the killer cell immunoglobulin-like receptors (KIR), controlled by a family of genes clustered in one of the most variable regions of the human genome — on chromosome 19q13.4. This study aimed to investigate the possible interplay between KIR allotype, B19 infection, and thyroid disorders. Thyroid gland tissue of 30 patients with autoimmune thyroid gland diseases (AITD), 30 patients with non-autoimmune thyroid gland diseases (non-AITD) and 30 deceased subjects whose histories did not show any of autoimmune or thyroid diseases (control group) were enrolled in the study. The presence of B19V, KIR2DL2/DS2, and KIR2DL3 was detected using PCRs (nPCR, PCR). The results showed that 28% of samples of thyroid tissue from patients with AITD and 67% with non-AITD were positive for the presence of B19V, in contrast only 5% control tissue samples harbored B19V DNA. B19V-positive AITD patients had higher frequency of KIR2DL2/DS2 homozygosity and lower frequency of homozygous KIR2DL3 genotype compared to B19V negative cases (33% vs 21% and 17% vs 46%, respectively). Although our data showed that B19V positive patients with AITD had a higher frequency of homozygosity for KIR2DL2/DS2, further studies with larger groups of patients are necessary to confirm the relationship between KIR, B19V and susceptibility to thyroid disease.