Hungarian Immunology

[Gene therapy as a treatment for rheumatoid arthritis]

JAMES M. Woods

JANUARY 10, 2004

Hungarian Immunology - 2004;3(01)

[A clear understanding of the pathogenic events and/or environmental conditions that lead to the development of rheumatoid arthritis has not been accomplished. In recent years, some of the most capable therapies have targeted individual proteins, such as proinflammatory cytokines, which contribute to persistent inflammation. The success of these therapies in some patients underscores the importance of having a solid pathophysiologic knowledge of the mechanisms at play in the diseased joint. Targeting the joint therapeutically with proteins or other agents has presented many challenges in the treatment of rheumatoid arthritis. To circumvent these obstacles, the idea of providing transgenes to cells of the synovial lining was born. This use of gene therapy, as a delivery vehicle rather than replacement of a genetic deficit, has had many successes in preclinical animal studies. Preliminary results of the first Phase I clinical trial in humans suggests that an ex vivo approach can be safe and enable transgene expression. This review provides a consolidated overview of many of the successful gene therapy strategies undertaken for the treatment of animal models of arthritis. The focus is on: 1. joint targeting strategies, including discussion on the local and systemic approaches as well as the contralateral joint; 2. the applicability of viral vectors, including comparison of adenoviral, retroviral, adeno-associated, and herpes simplex viruses; 3. timing and dosage of treatment; and 4. targets and candidate proteins that have been examined, including targeting proinflammatory cytokines or the use of anti-inflammatory cytokines.]



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Hungarian Immunology

[Experience with infliximab treatment of rheumatoid arthritis in Hungary]


[We conducted the first Hungarian open-label study using infliximab (Remicade) in 62 rheumatoid arthritis (RA) patients. The mean disease duration was 8.7 years. Patients receiving methotrexate for at least 3 months with active RA were included in the study. All patients received concomittant methotrexate treatment. Results indicated a 61%, 35% and 18% improvement in ACR20, ACR50 and ACR70, respectively. In most patients, dramatic improvement was seen as soon as after the first or second infusion.]

Hungarian Immunology

[TNF-α blocking therapy in rheumatoid arthritis]


[The research of pathomechanism of rheumatoid arthritis resulted in remarkable pragmatic results beyond the important theoretical knowledge. These observations led to the development of new effective agents, which were named as biological therapy and introduced in clinical praxis. The key factor of pathomechanism of rheumatoid arthritis is the proinflammatoric citokin TNF-α. It can be found on the top of the inflammation cascade where regulates many other inflammatory mediators and also plays an important role in the defence against infections and tumours. The author describes the TNF-α blocking agents used in clinical practice, their chemical and pharmacological feature, as well as their mode of action and the consequence of inhibition of TNF-α. He reviews the main results of the major clinical tests with infliximab, etanercet, and adalimumab. The results of these clinical studies demonstrate that the TNF-α blocking therapy gives clinical improvement in case of therapy resistant patients, decreases the number of swollen and tender joints, the pain, ESR and CRP, decreases the radiological progression, furthermore improves the quality of life. There are also some data about the favourable impacts observed during the early arthritis treatment. The TNF-α blocking therapy can be used effectively and safely in rheumatoid arthritis. In most cases the infusion reaction and the injection site reaction are not reasons for withdrawal from the study. The sideeffects, however, developed in increasing numbers during widespread applications. Among these the most important ones are the opportunist infection and the tuberculosis. In addition the sporadic occurrence of lupus-like symptoms, demyelinating disease, and aplastic anemia were reported. The fundamental requirements of the safety of the biological therapy are the professional indication and the careful monitoring during the treatment, the principle of which has been already prepared by the Professional College of the Rheumatology and Physiotherapy based on the international experience.]

Hungarian Immunology

[Intracytoplasmic cytokines in dermatomyositis]

ALEKSZA Magdolna, SZEGEDI Andrea, ANTAL-SZALMÁS Péter, SIPKA Sándor, DANKÓ Katalin

[OBJECTIVE - To investigate the intracellular and soluble cytokine levels in peripheral blood of patients with active and inactive dermatomyositis (DM). Methods The frequency of the intracellular IFN-g, IL- 4 and IL-10 expression of CD4+ or CD8+ cells were determined by flow cytometry. We measured the concentrations of soluble cytokines with commercial ELISAs. RESULTS - In active DM we observed decreased IFNg expression of CD4+ and CD8+ cells. These prominent changes disappeared in the inactive stage of the disease. In DM we could not detect a significant change in the intracellular IL-4 cytokine expression either in the active or in the inactive form. The IL-10 expression was elevated in the inactive state of the patients. CONCLUSION - We can state that a difference between aDM and iDM seems to exist in the level of peripheral blood lymphocytes and their intracellular cytokine content.]

Hungarian Immunology

[Cyclosporin A therapy of autoimmune urticaria]

IRINYI Beatrix, ZEHER Margit, HUNYADI János, SZEGEDI Andrea

[INTRODUCTION - In chronic idiopathic urticaria the etiology is unknown in spite of extensive investigations. In 27-50% of these cases autoimmune mechanisms are detected in the background. CASE REPORT - The authors demonstrate the case of an autoimmune urticaria patient with positive autologous serum skintest, who responded well to cyclosporin A therapy. CONCLUSION - According to the observation and the relevant literature, the authors also found small dose cyclosporin A therapy useful and safe in treating therapy resistant chronic urticaria.]

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Cyanocobalamin and cholecalciferol synergistically improve functional and histopathological nerve healing in experimental rat model

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Clinical Neuroscience

TLR4 (Toll-like receptor-4) expression and frontal-cingulate volumes in schizophrenia

LI Hua, KÉRI Szabolcs

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Lege Artis Medicinae

[The effect of biological therapy on generalised osteoporosis in patients with rheumatoid arthritis]


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Lege Artis Medicinae

[Combination of leflunomide and biologic agents in the treatment of rheumatoid arthritis]

SZŰCS Gabriella

[Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that leads to progressive joint destruction, functional disability and extra-articular complications. The initial approach to treatment of RA begins with the diagnosis, estimation of patient’s prognosis and the implementation of a therapeutic plan. Most important is early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs). Among the different protocols, combination therapies including methotrexate and/ or biologics seem to be more effective than monotherapies. Biological therapies introduced in recent years opened a new era in the treatment of RA. Randomized, controlled trials have demonstrated that the addition of methotrexate to biologic agents, such as tumor necrosis factor alpha (TNF-α) inhibitors generally increases their ability to retard structural damage, reduce disease activity and improve function. However, not all patients tolerate or respond to methotrexate. One of the most common used alternative DMARDs is leflunomide. Earlier several smaller retrospective studies, later prospective cohort studies, and finally two new populationbased longitudinal observational studies found that the above-mentioned parameters in RA patients treated with anti-TNF agents and leflunomide were similar to those receiving anti-TNF and methotrexate in combination. In addition, there were no significant differences in the frequency of adverse events between the groups. Taken together, leflunomide should be regarded as an effective and safe alternative in the treatment of rheumatoid arthritis.]

Hungarian Radiology

[A paradox of articular protective phenomenon: more serious-damaged rudimentary hand in rheumatoid arthitis]

SZÁNTÓ Dezső, SZŰCS Gabriella, DITRÓI Edit

[INTRODUCTION - The joints have been secured from rheumatoid arthritis by diminution of biomechanical effeciency. This effect was analyzed and named articular protective phenomenon three decades ago. CASE REPORT - A case of bilateral rheumatoid arthritis associated with unilateral developmental abnormality hand and bronchial asthma in a 35 year old female patient is presented. Her left 2nd, 3rd, 4th and 5th metacarpal bones moreover her fingers had not evolved. The patient has been treated by antiasthmatic steroid drugs for five years. Rheumatoid disorders of the affected left hand were more severe, than the abnormality of the normal upper limb. Eight years later the most severe bony lesions (ankylosis and mutilation) appeared on this side, only. CONCLUSION - The patient's hand was not saved by inborn bone defect in rheumatoid arthritis. The absence of articular protective phenomenon can be explained by the undisturbed innervation of limb, the motility of hypotrophic carpus besides to steroid-induced suppression.]