Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk

Funding Information: This study was supported by Rīga Stradiņš University Internal Research Grant Nr. 6-ZD-22/3/2022 “Identification of specific osteoarthritis phenotypes and disease endotypes tackled using the molecular and cellular assessment of the synovium-cartilage-bone interplay by correlation-based network analysis”. The article processing charge was covered by Rīga Stradiņš University Research Department. Publisher Copyright: © 2023 by the authors.Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These "foreign bodies" serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments-the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints.publishersversionPeer reviewe

Detecting knee cartilage structural changes using magnetic resonance computed vision analysis in patients with osteoarthritis : Preliminary results

Publisher Copyright: © 2021 Sciendo. All rights reserved.Based on epidemiological data, osteoarthritis (OA) is the most common joint disease of populations of industrialised countries. The increasing prevalence of OA is closely related to an ageing population and a sedentary lifestyle. Load-bearing joints, such as hip, knee, and intervertebral joints, are the primary ones that are being subjected to the degenerative changes. The pathophysiology of the disease is based on progressive damage and gradual deterioration of the micro and macrostructure of hyaline cartilage. In today's radiological practice, the first-line method for assessing the condition of articular cartilage is magnetic resonance imaging (MRI). However, the sensitivity of standard clinical MRI in articular cartilage assessment is limited. For this reason, for the last five years there has been a rapidly growing interest in developing advanced MRI techniques for cartilage structure evaluation. The purpose of this pilot study was to highlight the possibilities of Artificial Intelligence Computed Vision Analysis (MEDH 3.0 algorithm) in the evaluation of cartilage changes of the knee joint. The study was carried out at Rîga East Clinical University Hospital (RAKUS) and included 25 patients. After assessment by a rheumatologist, the participants were divided into two groups: 15 (60%) participants with OA and 10 (40%) healthy individuals. All patients underwent MRI examinations according to a unified RAKUS Gaiïezers Radiology clinic protocol. MRI data were analysed using the Computed Vision Analysis MEDH 3.0 algorithm. The results showed substantial differences in intensity variance (p < 0.01) parameters, as well as in pixel entropy and homogeneity values (p < 0.01). The results of the pilot study confirmed the potential use of Artificial Intelligence Computed Vision Analysis in further development and integration in the assessment of cartilage changes in the knee joint.publishersversionPeer reviewe

Concomitant multiple sclerosis and ankylosing spondylitis: : a clinical case report

Background: The therapy of patients with concomitant multiple sclerosis (MS) and ankylosing spondylitis (AS) is a challenge for clinicians. Secukinumab is effective in the treatment of MS. In the clinical case, we present, substantial clinical and radiological remission in the case of both autoimmune diseases was observed. Case Presentation: A male adult was diagnosed with relapsing-remitting MS. The patient complained of severe thoraco-lumbar pain. Magnetic resonance imaging (MRI) led to a diagnosis of AS. Considering that nonsteroidal anti-inflammatory drugs were ineffective and tumor necrosis factor-α blockers are contraindicated in patients with MS, secukinumab was prescribed. MRI 8 months after initiation of therapy provided clinical stability in consideration of the two autoimmune comorbidities. Conclusion: Secukinumab is an effective therapy for concomitant MS and AS.publishersversio

Cytokines and MMP-9 Levels in rheumatoid arthritis and osteoarthritis patients with persistent parvovirus B19, HHV-6 and HHV-7 Infection

Funding Information: This work was supported in part by the grant Nr. 09.0112 from Latvian Council of Science and by the National Research Programme in Biomedicine 2014–2017. Publisher Copyright: © 2019 Anda Kadiša et al., published by Sciendo 2019. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.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.Peer reviewe

Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis

Publisher Copyright: © 2016 by Anda Kadiša. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and-7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.Peer reviewe

Does the course of disease influence the development of fatigue in rheumatoid arthritis patients?

Publisher Copyright: © 2021 Sciendo. All rights reserved.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.publishersversionPeer reviewe

Latentas/persistentas parvovīrusa B19, HHV-6 un HHV-7 infekcijas iesaiste reimatoīdā artrīta etiopatoģenēzē un saistība ar klīnisko un radioloģisko atradi. Promocijas darba kopsavilkums

The Doctoral Thesis was carried out at the Linezers Clinic and the Gaiļezers Clinic of the Riga East Clinical University Hospital, the Hospital of Traumatology and Orthopaedics, RSU A. Kirhenšteins Institute of Microbiology and Virology and RSU Institute of Anatomy and Anthropology. Defence: at the public session of the Doctoral Council of Medicine on 18 January 2018 at 15.00 in Hippocrates Lecture Theatre, 16 Dzirciema Street, Rīga Stradiņš University.Rheumatoid arthritis (RA) is a chronic, progressive joint inflammation that causes destructive joint changes. RA reduces the quality of life and survival and creates a socio-economic burden. Despite long-term studies, the exact cause of the disease is unclear. As a contributing external factors include smoking, high caffeine consumption, frostbite and psycho-emotional or physical stress, as well as a variety of infectious agents - both bacteria and viruses. The most commonly studied viral agents are parvovirus B19 (B19V), rubella virus, human herpesviruses and others. The aim of the study was to compare RA patients with OA patients and healthy control subjects, and confirm or deny B19V, HHV-6 and -7 infections role in etiopathogenesis of RA, as well as to evaluate B19V, HHV-6 and -7 infectious activity of the different stages of the impact on RA clinical and laboratory activity, aggression and radiological stage. Persistent B19V, HHV-6 and -7 infection and the activity phases estimated using the nested PCR, and B19-specific antibodies were detected using recomWell and recomLine tests. Plasma cytokine expression estimated by ELISA. The results showed that RA patients have often B19V infection, the disease may begin not only temporarily after B19V infection but also as a consequence of prolonged B19V expression in the host tissues and chronic immune activation. Both active and acute B19V infection, by several clinical and laboratory parameters, affects both the disease activity and its aggression. RA patients’ T-cell proliferative response to B19V antigens is more common and more rapid compared to normal healthy subjects, indicating a persistent B19V infection in the presence of RA patients. Treatment with methotrexate (MTX) suppresses the T lymphocyte proliferative response to B19V antigens. The combination of sSMARM therapy also reduces the T lymphocyte proliferative response to B19V antigens. The persistence of different stages of B19V infection, as well as the duration of the infection before the patient is included in the study, have a slight effect on the clinical and laboratory progression of OA. The active HHV-6 and HHV-7 infection has a greater effect on RA activity, less aggression. Concomitant reactivation of HHV-6 and HHV-7 may result in a more aggressive RA course. The disease is also affected by HHV-6 and HHV-7 infection in the latent stage. The results of the study can be helpful in understanding RA’s development and in choosing a therapeutic strategy.The doctoral thesis was prepared with support of the State Research Programmes “Development of new prevention, treatment, diagnostic tools and methods, biomedical technologies for the improvement of public health (PUBLIC HEALTH)” 2010–2013 and “Biomedicine for public health (BIOMEDICINE)” 2014–2017

Involvement of Latent/Persistent Parvovirus B19, HHV-6 and HHV-7 Infections in Ethiopathogenesis of Rheumatoid Arthritis and Relationship with Clinical and Radiological Findings. Summary of the Doctoral Thesis

Promocijas darbs izstrādāts Rīgas Austrumu klīniskās universitātes slimnīcas klīnikā “Linezers” un klīnikā “Gaiļezers”, Traumatoloģijas un ortopēdijas slimnīcā, RSU A. Kirhenšteina Mikrobioloģijas un virusoloģijas institūtā un RSU Anatomijas un antropoloģijas institūtā. Aizstāvēšana: 2018. gada 18. janvārī plkst. 15.00 Rīgas Stradiņa universitātes Medicīnas promocijas padomes atklātā sēdē Rīgā, Dzirciema ielā 16, Hipokrāta auditorijā.Rheumatoid arthritis (RA) is a chronic, progressive joint inflammation that causes destructive joint changes. RA reduces the quality of life and survival and creates a socio-economic burden. Despite long-term studies, the exact cause of the disease is unclear. As a contributing external factors include smoking, high caffeine consumption, frostbite and psycho-emotional or physical stress, as well as a variety of infectious agents - both bacteria and viruses. The most commonly studied viral agents are parvovirus B19 (B19V), rubella virus, human herpesviruses and others. The aim of the study was to compare RA patients with OA patients and healthy control subjects, and confirm or deny B19V, HHV-6 and -7 infections role in etiopathogenesis of RA, as well as to evaluate B19V, HHV-6 and -7 infectious activity of the different stages of the impact on RA clinical and laboratory activity, aggression and radiological stage. Persistent B19V, HHV-6 and -7 infection and the activity phases estimated using the nested PCR, and B19-specific antibodies were detected using recomWell and recomLine tests. Plasma cytokine expression estimated by ELISA. The results showed that RA patients have often B19V infection, the disease may begin not only temporarily after B19V infection but also as a consequence of prolonged B19V expression in the host tissues and chronic immune activation. Both active and acute B19V infection, by several clinical and laboratory parameters, affects both the disease activity and its aggression. RA patients’ T-cell proliferative response to B19V antigens is more common and more rapid compared to normal healthy subjects, indicating a persistent B19V infection in the presence of RA patients. Treatment with methotrexate (MTX) suppresses the T lymphocyte proliferative response to B19V antigens. The combination of sSMARM therapy also reduces the T lymphocyte proliferative response to B19V antigens. The persistence of different stages of B19V infection, as well as the duration of the infection before the patient is included in the study, have a slight effect on the clinical and laboratory progression of OA. The active HHV-6 and HHV-7 infection has a greater effect on RA activity, less aggression. Concomitant reactivation of HHV-6 and HHV-7 may result in a more aggressive RA course. The disease is also affected by HHV-6 and HHV-7 infection in the latent stage. The results of the study can be helpful in understanding RA’s development and in choosing a therapeutic strategy.Promocijas darbs veikts ar Valsts pētījumu programmu “Jaunu profilakses, ārstniecības, diagnostikas līdzekļu un metožu, biomedicīnas tehnoloģiju izstrāde sabiedrības veselības uzlabošanai (PUBLIC HEALTH)”, 2010.–2013. gads, un “Biomedicīna sabiedrības veselībai (BIOMEDICINE)”, 2014.–2017. gads, atbalstu

Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis / Cilvēka Herpesvīrusa 6 Un 7 Infekcijas Ietekme Uz Reimatoīdā Artrīta Klīnisko Gaitu

Publisher Copyright: © 2016 by Anda Kadiša. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and-7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.Peer reviewe