Hungarian Immunology

[Alpha calcidol treatment in patients with psoriatic arthropathy: clinical and immunological effects]

GAÁL János, LAKOS Gabriella, ALEKSZA Magdolna, KISS Judit, HORVÁTH Irén, HORKAY Edit, NAGY Georgina, SZEGEDI Andrea

OCTOBER 20, 2007

Hungarian Immunology - 2007;6(05)

[OBJECTIVE - Our objective was to describe the functional changes of the immune system also to evaluate the clinical parameters during systemic alphacalcidol (1αOH vitamin D3) treatment in patients with psoriatic arthropathy. PATIENTS AND METHOD - Nineteen patients with peripheral polyarticular form of psoriatic arthropathy were investigated. Ten patients were treated with daily 2×25 mcg alphacalcidol per os for 6 months and the other 9 patients served as controls. Three visits (at start, 3 and 6 months later) were carried out during the study, changes in the laboratory and clinical parameters were examined and analysed statistically in the treated and control groups. RESULTS - In the peripheral blood of the treated group a statistically significant decrease in the percentage of CD3/CD69 positive activated and CD8 positive IFNγ producing T cells was observed and the serum level of IFNγ also showed a significant decrease during the first 3 months. Another three months later no change in the above mentioned variables could be detected. Additionally, there was a significant decrease in the clinical activity of the disease using DAS28 score during the whole 6 months follow up period. In the control group no significant changes were observed. CONCLUSION - Our results show that systemic alphacalcidol treatment has a notable immune modulatory effect on patients with psoriatic arthropathy. This effect is manifested in short-term temporary decrease of type 1 immune responses and continuous decrease in the disease activity.]



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[The role of endothelial cells]


[The role of endothelial cells is much beyond the well known barrier function between blood and tissues. Several different stimuli converge in the endothelial cells, which in turn regulate a number of vital processes in the organisms. Among these processes one of the most important is the immune response. Endothelial cells modulate the homing of leukocytes by the production of adhesion molecules and cytokines depending on activation state, anatomic location and vessel type. Endothelial cells express MHC and costimulatory molecules, which enables them to present antigens to T cells. Antigen presentation may lead to activation or tolerance of T cells depending on the phenotype of endothelial cells. They also express complement regulatory molecules and produce several complement cascade proteins. Endothelial cells take part in the catabolism of immunoglobulins as well as in the removal of circulating immune complexes. Finally, endothelial cells regulate inflammation at different levels by several mechanisms, which may substantially determinate the progression of the immune response.]

Hungarian Immunology

[Examination of leukocyte-endothel interactions in inflammatory animal models]

GONDA Andrea, MIKECZ Katalin, HUNYADI János

[Leukocyte influx into tissues is one of the hallmarks of physiological reactions to inflammatory stimuli, which is followed by a multistep process, resulting in leukocyte extravasation from the postcapillary venules. The different kinds of adhesion molecules, that play role in the rolling and firm adhesion of the leukocytes, have been investigated very intensively. By the help of animal models of inflammation, numerous individuals, being in the same stage of the disease, can be examined. The requirement for the adhesion molecules for inflammatory responses could be investigated with antibodies or, nowadays more often, gene knock out (KO) or transgenic mice. Beside evaluating the morphological and cytokine profile differences, using intravital microscopy is of great importance in the inflammatory experiments, while it allows observing interactions of virtually any blood cell types with the endothelial wall in vivo. The results are sometimes conflicting, indicating that the process of leukocyte-endothel interactions depends on different kind of other factors than the adhesion molecules, and still not fully understood.]

Hungarian Immunology

[Altered rate and absolute count of Th1/Th2 and Tc1/Tc2 lymphocytes in whole blood of patients with psoriasis]


[BACKGROUND - Psoriasis is a chronic inflammatory skin disorder characterised by an altered rate of interferon (IFN)-γ and interleukin (IL)-4 producing lesional and peripheral blood CD4+ and CD8+ T cells. To further characterise the imbalance of these cells and cytokines the rate and as a novel approach the absolute cell count (ACC) of IFN-γ+, IL-4+ and IL-10+ Thelper and Tcytotoxic cells was determined in the peripheral blood of psoriatic individuals. MATERIALS AND METHODS - Cell-associated cytokine expression was determined using intracellular cytokine staining and flow cytometry, serum cytokine levels were measured by enzyme linked immunosorbent assays (ELISAs) in the samples of 35 psoriatic patients and 15 controls. RESULTS - Significantly elevated rate (p<0.008) and ACC (p<0.009) of CD4+/IFN-γ+ cells was observed in the patients (28.3±8.8% and 237,216±134,154 cells/ml) compared to the healthy controls (21.0+ 6.8% and 135,772±50,212 cells/ml). In contrast the rate and the ACC of CD4+/IL-4+ cells decreased significantly in psoriasis (0.45±0.67% vs. 1.01± 0.48%, p<0.0001; 3,229±3,724 vs. 5,117±4,171 cells/ml, p<0.05). In the case of CD8+ T cells only the rate and the ACC of CD8+/IL-10+ cells increased significantly in patients compared to controls (5.49±5.42% vs. 1.59±0.78%, p<0.003 and 19,799±17,412 vs. 5,564±2,794 cells/ml, p<0.03). Though higher IFN-γ and lower IL-4 and IL-10 serum concentrations were detected in psoriasis these differences between patients and controls were not significant. Comparing the different cytokine parameters the serum cytokine levels showed some correlation only with the ACC and not with the rate of cytokine positive cells. CONCLUSIONS - These results further prove the presence of an altered balance in cytokine regulation towards the Thelper 1 cytokines in psoriasis, besides indicate that application of the ACC of cytokine positive helper and cytotoxic T cells as a novel parameter can help in the characterisation of these changes in different disorders.]

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[Overcome of bisphosphonate resistance with alphacalcidol: results of a one year, open follow-up study]

GAÁL János, BENDER Tamás, VARGA József, HORVÁTH Irén, KISS Judit, SOMOGYI Péter, SURÁNYI Péter

[INTRODUCTION - A considerable part of osteoporotic patients do not respond satisfactorily to adequate treatment with a bisphosphonate plus supplementation with calcium and conventional vitamin D3. This study intended to determine whether the replacement of vitamin D3 with alphacalcidol results in any BMD increase, i.e. is it possible to overcome resistance to bisphosphonates. PATIENTS AND METHOD - In 76 patients unresponsive to the combination of alendronate and conventional vitamin D3, the latter had been replaced with alphacalcidol (0.5 μg/day), and then the patients were followed up for a year. Clinical and laboratory parameters were recorded at baseline and after one year of treatment; and their changes were analysed by statistical methods. RESULTS - After treatment for one year, Wilcoxon test revealed a small but statistically significant (p<0.001) increase in the BMD values of the forearm (+2.2%) and lumbar vertebrae (+1.4%). At the end of the treatment period, the following, significant changes were observed compared to baseline (median values): serum calcium level increased by 0,06 mmol/l; serum phosphorus level decreased by 0.05 mmol/l, serum alkaline phosphatase activity decreased by 13 U/l, and urinary calcium/creatinine ratio in first-voided morning urine increased by 0.1. Additionally, serum PTH level decreased by 10.7 pg/ml (median). Serum levels of osteocalcin decreased by 0.4 ng/ml, along with the urinary D-Pyr /kreatinine ratio by 0.2 nmol/mmol (median). No significant increase of adverse events occurred. DISCUSSION - As suggested by our results, combination therapy with alendronate and alfacalcidol increases bone density and improves the biochemical markers of bone turnover - without any substantial increase in the incidence of adverse effects.]

Clinical Neuroscience

Cases of inborn errors of metabolism diagnosed in children with autism

CAKAR Emel Nafiye, YILMAZBAS Pınar

Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.

Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Clinical Neuroscience

Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

EVRAN Sevket, KATAR Salim

Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.