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Prediction of discontinuation of structured exercise programme in chronic fatigue syndrome patients.
(2020-10-26) Kujawski, Sławomir; Cossington, Jo; Słomko, Joanna; Dawes, Helen; Strong, James W. L.; Estevez-Lopez, Fernando; Murovska, Modra; Newton, Julia L.; Hodges, Lynette; Zalewski, Paweł
Purpose: The purpose of this study was to assess differences in the physiological profiles of completers vs. non-completers following a structured exercise programme (SEP) and the ability to predict non-completers, which is currently unknown in this group. Methods: Sixty-nine patients met the Fukuda criteria. Patients completed baseline measures assessing fatigue, autonomic nervous system (ANS), cognitive, and cardiovascular function. Thirty-four patients completed a home-based SEP consisting of 10–40 min per day at between 30 and 80% actual HR max. Exercise intensity and time was increased gradually across the 16 weeks and baseline measures were repeated following the SEP. Results: Thirty-five patients discontinued, while 34 completed SEP. For every increase in sympathetic drive for blood pressure control as measured by the taskforce, completion of SEP decreased by a multiple of 0.1. For a 1 millisecond increase in reaction time for the simple reaction time (SRT), the probability for completion of SEP also decreases by a multiple of 0.01. For a one beat HRmax increase, there is a 4% increase in the odds of completing SEP. Conclusion: The more sympathetic drive in the control of blood vessels, the longer the reaction time on simple visual stimuli and the lower the HRmax during physical exercise, then the lower the chance of SEP completion in ME/CFS.
Autonomic phenotypes in chronic fatigue syndrome (CFS) are associated with illness severity: A cluster analysis
(2020-08-05) Slomko, Joanna; Estevez-Lopez, Fernando; Kujawski, Sławomir; Zawadka-Kunikowska, Monika; Tafil-Klawe, Małgorzata; Klawe, Jacek J.; Morten, Karl J.; Szrajda, Justyna; Murovska, Modra; Newton, Julia L.; Zalewski, Paweł
In this study we set out to define the characteristics of autonomic subgroups of patients with Chronic Fatigue Syndrome (CFS). The study included 131 patients with CFS (Fukuda criteria). Participants completed the following screening symptom assessment tools: Chalder Fatigue Scale, Fatigue Impact Scale, Fatigue Severity Scale, Epworth Sleepiness Scales, the self-reported Composite Autonomic Symptom Scale. Autonomic parameters were measured at rest with a Task Force Monitor (CNS Systems) and arterial stiffness using an Arteriograph (TensioMed Kft.). Principal axis factor analysis yielded four factors: fatigue, subjective and objective autonomic dysfunction and arterial stiffness. Using cluster analyses, these factors were grouped in four autonomic profiles: 34% of patients had sympathetic symptoms with dysautonomia, 5% sympathetic alone, 21% parasympathetic and 40% had issues with sympathovagal balance. Those with a sympathetic-dysautonomia phenotype were associated with more severe disease, reported greater subjective autonomic symptoms with sympathetic over-modulation and had the lowest quality of life. The highest quality of life was observed in the balance subtype where subjects were the youngest, had lower levels of fatigue and the lowest values for arterial stiffness. Future studies will aim to design autonomic profile-specific treatment interventions to determine links between autonomic phenotypes CFS and a specific treatment.
Management of a primary malignant melanoma of uterine cervix stage IVA patient with radical surgery and adjuvant oncolytic virus Rigvir(R) therapy: A case report.
(2020-05-22) Pumpure, Elizabete; Dručka, Eva; Kigitoviča, Dana; Meškauskas, Raimundas; Isajevs, Sergejs; Nemiro, Ineta; Rasa, Agnija; Olmane, Evija; Zablocka, Tatjana; Alberts, Pēteris; Doniņa, Simona
Primary malignant melanoma of the uterine cervix is a rare disease with poor prognosis and high recurrence rate. We used Rigvir® as adjuvant therapy for a stage IVA patient. Tolerability, overall and progression-free survival are good.
Chemokine Receptors CCR1 and CCR2 on Peripheral Blood Mononuclear Cells of Newly Diagnosed Patients with the CD38-Positive Chronic Lymphocytic Leukemia
(2020-07-21) Kholodnyuk, Irina; Rivkina, Alla; Hippe, Laura; Svirskis, Simons; Kozireva, Svetlana; Ventina, Ildze; Spaka, Irina; Soloveichika, Marina; Pavlova, Jelena; Murovska, Modra; Lejniece, Sandra
Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical outcomes in patients with chronic lymphocytic leukemia (CLL) and is considered as the negative predictor of progression. In our study of newly diagnosed CLL patients, which included 39 CD38-positive and 22 CD38-negative patients, CCR1 and/or CCR2 were always detected, using flow cytometry, on the peripheral blood (PB) CD19+CD5+ lymphocytes in patients with >30% of the CD38+ CD19+CD5+ lymphocytes (n = 16). Spearman’s rank correlation analysis determined correlations between the frequency of the CCR1- and CCR2-expressing PB CD19+CD5+ lymphocytes and the frequency of the CD38-positive CD19+CD5+ lymphocytes (rs = 0.50 and rs = 0.38, respectively). No significant correlations were observed between ZAP70 mRNA expression levels in PB mononuclear cells and the frequency of the circulating CCR1+ or CCR2+ CD19+CD5+ lymphocytes. Further association studies are needed to verify prognostic relevance of the CCR1/CCR2 expression on leukemic cells in CLL patients at diagnosis. We suggest that CCR1/CCR2 signaling pathways could represent attractive targets for development of CLL anti-progression therapeutics.
Ultrastructural Characterization of the Frontal Lobe in the Case of Human Herpes Virus-6 Infection
(2020-06-24) Skuja, Sandra; Groma, Valerija; Murovska, Modra
The vast majority of the world’s population is exposed to beta-herpesviruses during early childhood. After the primary infection, human herpesvirus-6 (HHV-6) can establish a lifelong persistence. The role of HHV-6 in the development of neurodegenerative disorders is not completely clarified. Postmortem samples of brain tissue obtained from 24 elderly subjects with unspecified encephalopathy were used in the study. Nested (nPCR) and real-time polymerase chain reaction (RT PCR) were used for the qualitative and quantitative detection of viral genomic sequences in isolated DNA from frontal lobe samples. For ultrastructural examination, transmission electron microscopy (TEM), nPCR, and immunohistochemically confirmed HHV-6-positive tissue samples were used. Immunogold (IG) labeling using anti-HHV-6 (20) mouse monoclonal antibodies, raised against viral lysate (Santa Cruz Biotechnology, dilution 1:30), was performed. HHV-6 DNA was detected in 38% (9/24) of the frontal lobe tissue samples. The HHV-6 load in the nPCR-positive samples ranged from 10 to 3878.5 (copies/106 cells). A TEM examination of the frontal cortex revealed lipofuscin containing neurons, glial cells, unmyelinated and small myelinated axons, and symmetric synapses. Subcortical brain regions revealed glial cells interspersed by myelinated axons. The expression of viral proteins was found in the nuclei of neurons, demonstrating disarranged chromatin. HHV-6 positivity was detected between the adjacent cisternae of the rough endoplasmic reticulum of neurons displaying IG labeling. Furthermore, products of IG labeling were found in nuclei and cytoplasm of oligodendrocytes. The cytoplasm of astrocytes was IG labeled as well. IG labeling was used to determine the presence and intracellular localization of HHV-6 proteins in the human brain. HHV-6 possibly contributes to the demyelination process via entry into and affection of oligodendrocytes. Finally, neural susceptibility to HHV-6 may be linked to an invalid cellular immune response, followed by the development of a persistent viral infection.
Human parvoviruses may affect the development and clinical course of meningitis and meningoencephaliti
(2020-06-01) Vilmane, Anda; Terentjeva, Anna; Tamosiunas, Paulius L.; Suna, Normunds; Suna, Inga; Petraityte‐Burneikiene, Rasa; Murovska, Modra; Rasa-Dzelzkaleja, Santa; Nora- Krukle, Zaiga
Meningitis and meningoencephalitis are neurological inflammatory diseases, and although routine diagnostics include testing of a wide range of pathogens, still in many cases, no causative agent is detected. Human parvovirus B19 (B19V), human bocaviruses 1–4 (HBoV1–4), and human parvovirus 4 (hPARV4) are members of the Parvoviridae family and are associated with a wide range of clinical manifestations including neurological disorders. The main aim of this study was to determine whether human parvoviruses infection markers are present among patients with meningitis/meningoencephalitis in Latvia as well as to clarify the role of these viruses on the clinical course of the mentioned diseases. Our study revealed HBoV1–4 and B19V genomic sequences in 52.38% and 16.67% of patients, respectively. Furthermore, symptoms such as the presence of a headache and its severity, fatigue, disorientation, and difficulties to concentrate were significantly frequently present in patients with active parvovirus infection in comparison with parvoviruses negative patients, therefore we suggest that HBoV1–4 and B19V infection should be included in the diagnostics to reduce the number of meningitis/meningoencephalitis with unknown/unexplained etiology.
Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology
(2020-05-21) Estévez-López, Fernando; Mudie, Kathleen; Wang-Steverding, Xia; Bakken, Inger Johanne; Ivanovs, Andrejs; Castro-Marrero, Jesús; Nacul, Luis; Alegre, Jose; Zalewski, Paweł; Słomko, Joanna; Strand, Elin Bolle; Pheby, Derek; Shikova, Evelina; Lorusso, Lorenzo; Capelli, Enrica; Sekulic, Slobodan; Scheibenbogen, Carmen; Sepulveda, Nuno; Murovska, Modra; Lacerda, Eliana; on behalf of The European Network on ME/CFS (EUROMENE)
This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a backward-(reference lists) and forward-(citations) search of the works included in this review. Grey literature was addressed by contacting all members of the European Network on ME/CFS (EUROMENE). Independent reviewers searched, screened and selected studies, extracted data and evaluated the methodological and reporting quality. For prevalence, two studies in adults and one study in adolescents were included. Prevalence ranged from 0.1% to 2.2%. Two studies also included incidence estimates. In conclusion, studies on the prevalence and incidence of ME/CFS in Europe were scarce. Our findings point to the pressing need for well-designed and statistically powered epidemiological studies. To overcome the shortcomings of the current state-of-the-art, EUROMENE recommends that future research is better conducted in the community, reviewing the clinical history of potential cases, obtaining additional objective information (when needed) and using adequate ME/CFS case definitions; namely, the Centers for Disease Control & Prevention−1994, Canadian Consensus Criteria, or Institute of Medicine criteria.
Persistent Roseoloviruses Infection in Adult Patients with Epilepsy
(2020-05-11) Rasa-Dzelzkaleja, Santa; Gravelsina, Sabine; Chapenko, Svetlana; Nora-Krukle, Zaiga; Svirskis, Simons; Suna, Normunds; Kashuba, Elena; Karelis, Guntis; Murovska, Modra
Background: Human herpesviruses (HHV)-6A, HHV-6B and HHV-7 are considered to be involved in the pathogenesis of epilepsy, a common neurological disorder. The objective of this study was to determine the association of roseoloviruses infection with epilepsy. Methods: 53 epilepsy patients and 104 ordinary blood donors were analyzed to determine presence of virus-specific antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA), genomic sequences, viral load and gene expression by polymerase chain reactions (PCRs) and restriction analysis, HHV-6 protein expression by IFA and level of cytokines by ELISA. Results: Roseoloviruses genomic sequences in DNA samples from whole blood were found in 86.8% of patients versus 54.8% of controls and active infection was revealed only in patients with epilepsy (19.6% of roseolovirus-positive patients). Significantly higher viral load and more frequent gene expression was detected in patients compared to the controls. HHV-6-encoded protein expression was demonstrated in 53.3% of patients with previously detected HHV-6 DNA. Changes in level of cytokines were determined in patients with elevated viral load compared to the patients without elevated viral loads and to the controls. Conclusions: Results on frequent active HHV-6 and HHV-7 infection in epilepsy patient’ peripheral blood indicate on possible involvement of these viruses in the disease development.
The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE)
(2020-04-07) Pheby, Derek F.H.; Araja, Diana; Berkis, Uldis; Brenna, Elenka; Cullinan, John; de Korwin, Jean-Dominique; Gitto, Lara; Hughes, Dyfrig A; Hunter, Rachael M; Trepel, Dominic; Wang-Steverding, Xia
We have developed a Europe-wide approach to investigating the economic impact of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries. The economic burden of ME/CFS in Europe appears large, with productivity losses most significant, giving scope for substantial savings through effective prevention and treatment. However, economic studies of ME/CFS, including cost-of-illness analyses and economic evaluations of interventions, are problematic due to different, arbitrary case definitions, and unwillingness of doctors to diagnose it. We therefore lack accurate incidence and prevalence data, with no obvious way to estimate costs incurred by undiagnosed patients. Other problems include, as for other conditions, difficulties estimating direct and indirect costs incurred by healthcare systems, patients and families, and heterogeneous healthcare systems and patterns of economic development across countries. We have made recommendations, including use of the Fukuda (CDC-1994) case definition and Canadian Consensus Criteria (CCC), a pan-European common symptom checklist, and implementation of prevalence-based cost-of-illness studies in different countries using an agreed data list. We recommend using purchasing power parities (PPP) to facilitate international comparisons, and EuroQol-5D as a generic measure of health status and multi-attribute utility instrument to inform future economic evaluations in ME/CFS
Cells and Cytokines in Milk of Subclinically Infected Bovine Mammary Glands after the Use of Immunomodulatory Composition GLP 810
(2020-03-10) Gulbe, Gundega; Pilmane, Māra; Saulīte, Vaira; Doniņa, Simona; Jermolajevs, Jevgenijs; Peškova, Lilija; Valdovska, Anda
The aim of this study was to investigate the effect of intramammary infusions of natural composition GLP 810 with immunomodulating properties on the local nonspecific cellular and humoral immune response in cows with subclinical mastitis. The composition GLP 810 consists of lactic acid, lysozyme, glycopeptides, and 0.9% solution of NaCl. The following parameters were studied: (1) leukocyte differential distribution in milk, (2) expression of cytokines in milk leukocytes, (3) antibacterial activity, and (4) milk quality. Nineteen mammary glands in five lactating cows were infused with 10 mL of GLP 810, and nineteen other glands from five control cows were treated with 10 mL 0.9% NaCl. The results showed that after intramammary administration of the composition GLP 810 three times with 48 h intervals, the following effects on leukocyte populations in milk were observed: (1) an increase in the number of polymorphonuclear leukocytes and lymphocytes and (2) a decrease in the number of macrophages. A reduction in the number of pathogenic bacteria was also detected. The analyses of tumour necrosis factor-alpha, interleukin-10, and beta-defensin-2 revealed that the production of the aforementioned cytokines significantly increased, whereas no significant effects on interleukin-1 and caspase-6 expression in milk leukocytes were recorded. However, there were significant differences between mammary glands with high and low milk somatic cell count. The results suggest that the composition GLP 810 has an immunomodulatory effect on mammary glands and it could be used for improving the immune response in cows with subclinical mastitis during lactation.
The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients
(2019-12-19) Zalewski, Paweł; Kujawski, Sławomir; Tudorowska, Malwina; Morten, Karl; Tafil-Klawe, Małgorzata; Klawe, Jacek J.; Strong, James; Estévez-López, Fernando; Murovska, Modra; Newton, Julia L.; The European Network on ME/CFS (EUROMENE)
Background: Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined. Methods: Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment. Results: Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p = 0.045, r = 0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p = 0.02, omega = 0.03, p = 0.007, r = 0.34 and p = 0.004, r = 0.35, respectively. Non-significant changes were noted in other cognitive tests. Conclusions: A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli
COVID-19: the third wave of coronavirus infection outbreak.
(2020-05-08) Sokolovska, Lība; Sultanova, Alīna; Cistjakovs, Maksims; Murovska, Modra
The novel coronavirus SARS-CoV-2 poses a great public health crisis. As of December 2019, it has spread all over the world with cases reported in more than 100 countries and the number of infected individuals surpassing 1,000,000. On March 11 World Health Organization officially characterized the COVID-19 as a pandemic. Although genetic analysis revealed some similarities between the novel coronavirus and the causative agent of the 2002 SARS epidemic, both viruses have significant differences. Research done on SARS-CoV has greatly aided the understanding of SARS-CoV-2, as it served as a knowledge base and helped to identify the cell entry receptor and some other features of the disease, but not all of them. Several critical questions remain unanswered and specific therapeutics and vaccine candidates are lacking.
Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
(2018) Rasa, Santa; Nora-Krukle, Zaiga; Henning, Nina; Eliassen, Eva; Shikova, Evelina; Harrer, Thomas; Scheibenbogen, Carmen; Murovska, Modra; Prusty, Bhupesh K.; The European Network on ME/CFS (EUROMENE)
Background and main text Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. Conclusions This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.
Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review
(2018) Estévez-López, Fernando; Castro-Marrero, Jesus; Wang, Xia; Bakken, Inger Johanne; Ivanovs, Andrejs; Nacul, Luis; Sepúlveda, Nuno; Strand, Elin B; Pheby, Derek; Alegre, Jose; Scheibenbogen, Carmen; Shikova, Evelina; Lorusso, Lorenzo; Capelli, Enrica; Sekulic, Slobodan; Lacerda, Eliana; Murovska, Modra; on behalf of the European Network on ME/ CFS (EUROMENE)
Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease involving central nervous system and immune system disorders, as well as cardiovascular abnormalities. ME/CFS is characterised by severe chronic fatigue lasting for at least 6 months, including clinical symptoms such as tender cervical or axillary lymph nodes, muscle pain, joint pain without swelling or redness, post-exertional malaise for more than 24 hours and unrefreshing sleep. Studies on the epidemiology of ME/CFS in Europe only include single countries and, therefore, the prevalence and incidence of ME/CFS in Europe (as a whole) is unknown. One of the purposes of the European Network on ME/CFS (EUROMENE; European Union-funded COST Action; Reference number: 15111) is to address this gap in knowledge. We will systematically review the literature reporting figures from European countries to provide a robust summary and identify new challenges. Methods and analysis We will systematically search the literature databases Scopus, PubMed and Web of Science for studies published in the last 10 years (ie, after 2007). No language restriction will be applied. Two independent reviewers will search, screen and select studies as well as extract data about their main characteristics and evaluate their methodological and reporting quality. When disagreements emerge, the reviewers will discuss to reach a consensus. We plan to produce a narrative summary of our findings as we anticipate that studies are scarce and heterogeneous. The possibility of performing meta-analyses will be discussed in a EUROMENE meeting. Ethics and dissemination Ethical approval is not required as only publicly available data will be included. Findings will be described in EUROMENE reports, published in peer-reviewed journal(s) and presented at conferences. The findings will be also communicated to policy-makers, healthcare providers, people with ME/CFS and other sections of society through regular channels including the mass-media.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
(2018) Sotzny, Franziska; Blanco, Julià; Capelli, Enrica; Castro-Marrero, Jesús; Steiner, Sophie; Murovska, Modra; Scheibenbogen, Carmen; on behalf of the European Network on ME/CFS (EUROMENE)
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanismis incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects forME/CFS. Immune dysregulation inME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity.Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severemetabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.
Proportion of the CD19-Positive and CD19-Negative Lymphocytes and Monocytes within the Peripheral Blood Mononuclear Cell Set Is Characteristic for Rheumatoid Arthritis
(2019) Kholodnyuk, Irina; Kadisa, Anda; Svirskis, Simons; Gravelsina, Sabine; Studers, Peteris; Spaka, Irina; Sultanova, Alina; Lejniece, Sandra; Lejnieks, Aivars; Murovska, Modra
Background and objectives: Composition of the peripheral blood (PB) cell populations and their activation state reflect the immune status of a patient. Rheumatoid arthritis (RA) is characterized by abnormal B- and T-cell functions. The objective of this study was to assess the profiles of the PB mononuclear cell (PBMC) populations in patients with rheumatoid and osteoarthritis (OA) in comparison with healthy control (HC) subjects in order to evaluate the PBMC profiles as a potential diagnostic characteristic in RA. The second aim was to assess the CCR1 and CCR2 expression on PB lymphocytes and correlate it with the plasma levels of matrix metallopeptidase 9 (MMP-9), IL-17F, TNF-α, IL-6, and IL-10. Materials and Methods: The frequency and phenotype, including CCR1 and CCR2, of the PBMC populations (monocytes, CD19+B cells, and T/NK lymphocytes) in RA (n = 15) and OA (n = 10) patients and HC (n = 12) were analyzed by five-color flow cytometry. DNA of the viruses, HHV-6, HHV-7, and B19, in the whole blood and cell-free plasma, were assessed by nested-polymerase chain reaction (PCR). Results: Active persistent or acute infections, caused by HHV-6, HHV-7, or B19, were not detected in patients of this study. Both CCR1 and CCR2 were determined on the PB B and T/NK lymphocytes in several RA and OA patients and HCs. However, in patients, the frequency of the CCR1-positive T/NK lymphocytes showed a weak negative correlation with the IL-10 level, while the frequency of the CCR2-positive B cells correlated positively with the level of IL-6. Statistically significant differences in the proportions of the CD19-positive and CD19-negative lymphocyte and monocyte subsets within the PBMC set were determined between RA and OA patients and HC adults. Conclusions: We have shown in our pilot study with rather small cohorts of patients that the PBMC-population profiles were very consistent, and statistically significantly differed between RA and OA patients and HC subjects.
Association of Human Parvovirus B19 Infection with Development and Clinical Course of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
(2019) Rasa-Dzelzkalēja, Santa; Čapenko, Svetlana; Krūmiņa, Angelika; Yung-Cheng, Lin; Murovska, Modra
Our aim was to estimate the presence of B19V infection markers, the level of cytokines and time period since the appearance of infection in association with ME/CFS clinical symptoms. In 200 ME/CFS patients and 104 control group individuals the presence of B19V-specific IgG/IgM class antibodies, B19V NS1 gene sequence, mRNA expression, viral load and level of cytokines were determined. B19V-specific IgG-antibodies were found in 70% of ME/CFS patients and 67.4% of controls, IgM-antibodies in 8% of patients and in none of controls, B19V genomic sequences in 29% of patients and 3.8% of controls. 58.6% of positive patients had active and 41.4% had latent/persistent B19V infection. B19V NS1 gene expression was detected in 43% of patients. B19V load varied from < 0.2 copies to median 38.2 copies/µg of DNA. According to the antibody pattern, 36% of patients had a recent, and 43% had sustained B19V infection. Patients with the B19V genomic sequence and NS1 specific antibodies significantly more often had lymphadenopathy and multi-joint pain. Onset of the symptoms corresponded to time of appearance of B19V infection. IL-10 and TNF-levels were higher in patients with elevated B19V load. B19V genome 1 was identified in Latvian ME/CFS patients. The results indicated that at least in some cases B19V infection plays an important role in ME/CFS development
Synovitis in Osteoarthritic Patients: Morphological and Virological Evidence of its Contribution to Development of the Disease
(2019) Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Murovska, Modra; Groma, Valērija
The role of inflammation in the development of osteoarthritic joint degeneration is not completely understood. Recent data suggest that processes that cause and orchestrate inflamed synovial lesions may be implicated in the development of the disease. The morphological changes of the synovium in patients with osteoarthritis (OA), as well as the level of synovial inflammation cautiously graded, in association to the presence of human parvovirus B19 (B19V) infection markers, were evaluated. Qualitative and quantitative detection of B19V genomic sequence was performed in OA and rheumatoid arthritis (RA) groups. The expression of CD68, S100 (Ca2+ binding proteins soluble in 100% ammonium sulfate) and B19 VP1/VP2 capsid proteins found in the synovium were investigated by single and double immunolabeling, whereas fine features of synoviocytes — by electron microscopy. One-third of OA and RA patients demonstrated synovial expression of B19V antigen, which was confirmed in both types of synoviocytes. The overall expression of B19V in OA patients was weaker than that found in RA subjects. Positive correlation between B19V-positive vascular endothelial cells, sublining infiltrating lymphocytes, macrophages, and B19V-positive synoviocytes was established. No correlation between synovitis score indices as well as the expression of S100 and expression of B19V was found. The results suggest that the synovial membrane maintains local joint homeostasis, and that virus mediated synovitis is implicated in the development of OA.
Cytokines and MMP-9 Levels in Rheumatoid Arthritis and Osteoarthritis Patients with Persistent Parvovirus B19, HHV-6 and HHV-7 Infection
(2019) Kadiša, Anda; Nora-Krūkle, Zaiga; Švirskis, Simons; Studers, Pēteris; Girkontaite, Irute; Lejnieks, Aivars; Murovska, Modra
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosive changes and ankylosis of joints and may cause internal injuries. Osteoarthritis (OA) is a degenerative process of the articular cartilage. However, inflammatory mediators may play a pivotal role in the initiation and perpetuation of the OA process. It is necessary to continue to study possible factors that may promote the development of the disease. The goal of this study was to evaluate the frequency and activity stage of parvovirus B19 (B19V) and persistent human herpes virus (HHV)-6 and HHV-7 infection in RA and OA patients, and healthy persons, in relation to cytokine levels and presence or absence of viral infections. RA patients with active B19V infection had the highest levels of tumour necrosis factor alpha (TNF-α), which may contribute to the development of RA. In the case of OA, the TNF-α level was higher in patients with active persistent B19V infection, suggesting that B19V reactivation affects also OA. Interleukin (IL)-6, IL-10 and metalloproteinase (MMP)-9 levels were higher in RA patients with latent HHV-6/-7 infection in comparison with active HHV-6/-7 infection, whereas in OA patients levels of all studied cytokines were very variable, ranging from low to high but without significant differences. This suggests that also latent HHV-6 and -7 viral infections can promote development of RA.
Monocytes/Macrophages Act as Mediators for Human Herpesvirus-6 Infection of Thyroid Gland in Patients with Autoimmune Thyroiditis
(2019) Sokolovska, Lība; Sultanova, Alina; Čistjakovs, Maksims; Cunskis, Egils; Murovska, Modra
The aim of this study was to investigate the possibility of using monocytes/macrophages as mediators in human herpesvirus-6 (HHV-6) infection of thyroid gland tissues in autoimmune thyroiditis (AIT). Seventy-three AIT patients were enrolled in this study. The control group consisted of 80 blood donors. Monocyte/macrophage isolation for AIT patient samples was performed by adherence. HHV-6 was detected in peripheral blood mononuclear cell (PBMC) DNA samples using nested polymerase chain reaction (nPCR). Gene expression of HHV-6 active infection marker (U79/80) and chemokine receptors (U12, U51) in patient monocyte/macrophage samples and blood donor PBMC samples was detected using reverse-transcription PCR. HHV-6 viral load was detected by using quantitative-PCR technique. The HHV-6 genomic sequence was found significantly more frequently among AIT patient than control group samples. Markers of active infection were found in 8 AIT patient monocyte/macrophage samples (11%) and in none of control group PBMC samples. HHV-6 U51 mRNA expression was detected only in AIT patient samples (2/24 previously positive for HHV-6). Since HHV-6 genomic sequences were found significantly more frequently in AIT patient samples and active infection markers were found in patient monocytes/macrophages, our results suggest that monocytes/macrophages may be used by HHV-6 as mediators for thyroid gland infection.

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