Hungarian Immunology

[Molecular mechanisms and clinical importance of the RANK - RANK ligand - osteoprotegerin system]


MARCH 20, 2006

Hungarian Immunology - 2006;5(02)

[The receptor activator of nuclear factor κB ligand (RANKL) is an essential cytokine for the formation and activation of osteoclasts. RANK, expressed on osteoclasts, interacts with RANKL, produced by osteoblasts and stromal cells. RANK-RANKL interaction is involved in osteoclastogenesis and bone resorption underlying metabolic bone diseases, arthritis, malignant bone disorders and some vascular diseases. Osteoprotegerin (OPG) physiologically counterbalance the action of RANKL. Several factors including estrogens, citokines and others regulate the RANKL-OPG ratio and thus bone resorption. RANKL blockade using recombinant OPG or anti-RANKL antibody may prevent bone loss in osteoporosis, chronic inflammatory and vascular disorders, as well as tumors. Active vaccination and gene therapy are further future perspectives in therapy. All these treatment modalities may be included in the future management of bone and vascular diseases.]



Further articles in this publication

Hungarian Immunology

[Paraneoplastic diseases of the locomotor system]


[Paraneoplasias in rheumatology can be present in different forms of arthropathies, myopathies. In addition, we often see atypical forms of systemic autoimmune diseases. Vasculitis is mainly associated with lymphoproliferative diseases. The direct invasion of bones and joints is not present in paraneoplasia, as this entity is a collection of symptoms generated by the tumour itself by producing biologic mediators, hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplasia is of outmost importance because it attires attention to the presence of tumour in the organism and thus enables us for early treatment of the malignancy. Monitoring of the severity of paraneoplastic symptoms serves as a marker for determination of efficacy of the targeted oncological therapy. On the other side, because these severe symptoms affect the patient's quality of life and can lead even to death their in time recognition and treatment is extremely important.]

Hungarian Immunology

[Familial autoinflammatory syndromes]

ORBÁN Ilonka, BALOGH Zsolt

[A group of rare inherited disorders, the familial autoinflammatory syndromes are characterised by attacks of seemingly unprovoked inflammation without significantly elevated autoantibody and autoreactive T cell levels. The rare diseases are present from infancy to lifelong, with periodic fever attacks and usually are accompanied by recurrent systemic inflammatory symptoms such as abdominal pain, diarrhoea, rash, arthralgia, polyarthritis, polyserositis, ocular disorders are separated by symptom-free intervals. Referred to as hereditary periodic fever syndromes appear by spontaneous crisis attacks and reveal a severe acute-phase response during the fever. In their pathogenesis there are no evidence neither of infection nor the common characteristics for autoimmune diseases: the production of high-titer auto-antibodies and antigenspecific T cell activation. The basic disease mechanism consists of the recently identified mutations in genes enconding important proteins: pyrin, cryopyrin, tumour necrosis factor (TNF) receptor and other mediators of apoptosis, inflammation and morbid citokine processing. The differential diagnosis of the diseases is not easy, their treatment is not resolved, although in same cases the biological treatment may be efficacious.]

Hungarian Immunology

[The role of nerve growth (NGF) factor in the immune and inflammatory events and in autoimmune thyroid diseases]


[Nerve growth factor (NGF) is a neurotroph cytokine, and beside its effect on the central and peripheral nervous systems NGF plays an important role in the inflammatory and autoimmune processes. There are two types of NGF receptors, the high-affinity (TrkA) and the low-affinity (p75), which activations via signal transduction could lead to the inhibition or induction of apoptosis. Suppression of apoptosis could be induced by cytokines, hormones, antioxidans and increased intracellular Ca2+-levels. In the pathogenesis of many autoimmune diseases (systemic lupus erythematosus, 1-type diabetes mellitus, multiple sclerosis) could detect elevated serum levels of NGF associated with the disease activity. Our study demonstrated increased levels of NGF in autoimmune thyroid diseases (Graves’ disease, Hashimoto’s thyroiditis) in comparison with the controls. Decreased serum levels of NGF were found in Graves’ ophthalmopathy suggesting the role of apoptosis in the development of the eye symptoms. Orbital tissues are characterized with the high expression of TrkA receptors. NGF plays an important role in the pathomechanisms of neuro-immuno-hormonal diseases and its knowledge may be helpful in the diagnosis and therapy.]

Hungarian Immunology

[Clinical and immunoserological characteristics of mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH)]

VÉGH Judit, CSÍPŐ István, UDVARDY Miklós, KAPPELMAYER János, LAKOS Gabriella, ALEKSZA Magdolna, ZEHER Margit, SZEGEDI Gyula, BODOLAY Edit

[INTRODUCTION - The authors investigated the clinical characteristics, survival, accumulated damage index and immunoserological abnormalities in patients with mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS - Anti-U1RNP autoantibodies, anti-endothelial cell antibodies, anti-cardiolipin antibodies and serum trombomodulin as well as von Willebrand factor antigen concentrations were measured in 25 patients with MCTD associated with PAH (11 right heart catheterization and 14 Doppler echocardiography) and in 154 MCTD patients without PAH. Changes in arterial pulmonary pressure were followed up by echocardiography. RESULTS - In the 25 patients PAH followed MCTD diagnosis in the average 11.6±4.5 years of the diseases. The probability of survival was lower in MCTD patients with PAH than in the 154 non-PAH MCTD patients (five years survival rate in MCTD with PAH: 73.39%, vs. 96.43% in non PAH MCTD; p<0.01; 10 years survival rate 86.74% vs. 93.25%; p<0.01). Anti-endothelial cell antibodies were more frequently present in MCTD patients sera with PAH than in non PAH MCTD (p<0.001). Serum trombomodulin and vWFAg levels were higher in MCTDPAH patients than in non PAH MCTD patients (trombomodulin:34.2±15.3 ng/ml vs. 11.8±6.5 ng/ml; p<0.001; vWFAg: 311.1±147% vs. 172.5± 141%. Significant correlations were noticed between the quantity of anti-endothelial cell antibodies and serum trombomodulin level (r=0.466) as well as the quantity of anti-endothelial cell antibodies and vWFAg serum level (r=0.550). CONCLUSION - Survival probability was worse for MCTD patients with PAH than for non PAH MCTD patients. Our results suggest that in MCTD the presence of anti-endothelial cell antibodies and endothelial cell activation may play a role in the development of pulmonary arterial hypertension and in the maintenance of obliterative vascular processes.]

All articles in the issue

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[Estimating the risk of new fracture - Which factors confer an increased fracture risk?]


[This risk of osteoporosis-related fractures is influenced by a number of well-known risk factors. Among the approaches to quantify bone fracture risk, the FRAX questionnaire is the most widespread in everyday practice. However, this method only provides a probability percentage for the physician, and it is unable to specify or weigh the factors that may have a particular importance in evaluating individual fracture risk, or choosing the appropriate therapy in patients with previous osteoporotic fracture. This summary aims to provide practical help for the evaluation of individual fracture risk in patients who have had bone fractures.]

LAM Extra for General Practicioners

[Recognition of the characteristics of rare types of arthritis]

ROJKOVICH Bernadette, MÉSZÁROS Györgyi

[Recognition of the characteristics of arthritis is crucial for making a correct diagnosis. Several aspects of the history and physical examination could help the diagnosis, such as the mode of onset (acute, insidious), duration of symptoms (self-limiting, chronic), number of affected joints (mono-, oligo-, polyarthritis), distribution of joint involvement (symmetrical, asymmetrical), localisation of affected joints (axial, peripherial) and sequence of involvement (additive, migratory, intermittent). Other important aspects for the correct diagnosis are the characteristics of the patient (gender, age, family history) and the presence or absence of extra-articular features of disease. The articular pattern may change with time in the course of a disease, and the single clinical pattern of joint disease may correspond to more than one diagnosis. Evidence of some distinct articular patterns may limit the spectrum of diagnostic options and reduces unnecessary diagnostic testing. The diagnostic process may require the addition of laboratory examination, imaging techniques, and other tests to refine the analysis. In this article, we report a case where joint punction and histological elucidation was necessary to make the correct diagnosis, because a syndrome of acute, destructive sterile arthritis mimicking articular infection might be present in a variety of joint disorders. In this paper, we highlight those characteristics that are distinctive for particular rheumatological disorders, in order to help starting treatment early.. In a substantial number of patients the cause of the diseases remains undetermined. However, a detailed anamnesis and physical examination remain the cornerstone of a diagnostic evaluation. ]


[Effect of cigarette smoking on bone density]


[INTRODUCTION - Smoking is associated with a decreased bone mass and increased risk of osteoporotic fractures.The aim of this study was to investigate the impact of current tobacco smoking to bone mineral density (BMD) in Hungarian females. PATIENTS AND METHODS - We measured BMD in 43 (25-72 yrs) smoker and 43 age- and BMI-matched non-smoker women by dual X-ray absorptiometry (Prodigy, GE Lunar) at the lumbar spine and proximal femur and by single photon absorptiometry at the radius midshaft of the non-dominant side (NK 364, Gamma). RESULTS - Osteoporosis (T-score at any measured site below - 2.5) was found to be more common among smokers compared to non smokers (63.6% vs 36.4%, χ2-test p=0.009). Among premenopausal women no difference was found in BMD between the two groups, whereas postmenopausal smoker women tended to have a lower BMD value compared to those who didn’t smoke. In postmenopausal women a decrease of borderline significance was found in lumbar BMD (0.977 vs 1.04; p=0.06). CONCLUSION - Our observation suggests that there is only a slight decrease in bone mass due to smoking, however, added to menopausal bone loss this effect can be a significant contributor to the increased fracture risk of involutional age.]


[Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures]


[Percutaneous vertebroplasty is a minimally invasive procedure that is increasingly applied for the treatment of osteoporotic compression fractures. The authors discuss its indications, patient selection criteria, the issue of diagnostic imaging, the technique of the procedure, its potential complications, review the literature on post-procedure pain relief, and briefly present their own experience in the treatment of osteoporotic fractures. Vertebroplasty is indicated for patients with severe, persistent, often incapacitating focal back pain not responding to standard medical therapy, which is related to the collapse of one or more vertebral bodies. Patients selected carefully by the clinical symptoms and the imaging studies usually respond promptly to the treatment, experience significant pain relief, improvement of the quality of life, and an increase in mobility.Vertebroplasty is a safe procedure with relatively low complication rates.The potential neurological complications, however, necessitate an instantly available neurosurgical background.]


[Does the vitamin K2 play a role in the prevention or treatment of osteoporosis? - a systematic review]

SZILI Balázs, TAKÁCS István

[The physiological role of vitamin K in blood clotting and bone metabolism is well known. A number of articles have been published recently about the effects of vitamin K2 on bone. Non-professional media promotes vitamin K2 as a potent tool for the prevention and treatment of osteoporosis. Nevertheless vitamin K2 is not included in either Hungarian, or European, or Ameri­can guidelines as an anti-osteoporotic me­dication. Our aim was to review the literature and provide a systematic review on the role of vitamin K2 in the prevention and treatment of osteoporosis. We have searched articles on available on 14. February 2014. Our search terms were: („vitamin K2” OR „menaquinon” OR „MK-7” OR „menantrenon”) AND „osteoporosis”. We have only reviewed original articles that discussed the relationship of vitamin K2 and osteoporosis, and had at least the abstract available in English. Of the 155 articles found, 135 had a relevant topic, 126 had at least the abstract in English. Of these, 73 were original articles, including 44 human studies (8 double-blind, controlled, 26 open-label, controlled, 5 observational and 5 cross-sectional studies) and 29 animal or in vitro models. In the non-Asian population there is no evidence for fracture-preventing or BMD-increasing effect of vitamin K2 treatment. The currently recommended anti-osteoporotic medications are significantly more efficient compared with the BMD increase observed in some Asian studies. ]