Hungarian Immunology

[Familial autoinflammatory syndromes]

ORBÁN Ilonka, BALOGH Zsolt

MARCH 20, 2006

Hungarian Immunology - 2006;5(02)

[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.]

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[Paraneoplastic diseases of the locomotor system]

ANDRÁS Csilla, SZÁNTÓ János, SZEKANECZ Zoltán, CSIKI Zoltán, ILLÉS Árpád, SZEKANECZ Éva, DANKÓ Katalin

[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.]

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[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.]

Hungarian Immunology

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

MOLNÁR Ildikó

[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.]

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[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.]

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