South East European Journal of Immunology

Number 1, 2015

1-4
Late Diagnosis of Takayasu Arteritis with Cardiac Involvement: Case Report

Authors: Maja Stojanović, Aleksandra Perić-Popadić, Sanvila Rašković, Jasna Bolpačić, Maja Vučković, Vesna Tomić Spirić, Mirjana Bogić

Abstract

View in PDF

Number of views: 546

Takayasu arteritis (TA) is an idiopathic chronic granulomatous vasculitis that affects aorta, its main branches and occasionally pulmonary arteries. It is more common in Asian persons, affecting predominantly young women. Clinical presentation is nonspecific at the beginning of the disease, while in the ischemic disease’s stage it depends on the territories affected. We present the case of a 26-year-old woman who was diagnosed as having TA. Multiple vascular abnormalities of aorta and its branches and severely reduced left ventricular function were present at the time of diagnosis. Immunosuppressive treatment consisting of prednisone and azathyoprine along with conventional heart failure therapy significantly improved her cardiac function.

5
KIR Gene Frequencies in Women with Infertility Problems

Authors: Eli Djulejic, Aleksandar Petlichkovski, Dejan Trajkov, Gligor Dimitrov, Sonja Alabakovska

Abstract

View in PDF

Number of views: 673

BACKGROUND: Natural killer (NK) cells are the predominant lymphocyte population in the decidua. Being the most abundant leucocytes, the activity of NK cells is important in different immuno-pathological conditions, such as recurrent spontaneous abortions, infertility and problems in implantation. The NK cells recognize HLA class I molecules on trophoblasts trough killer immunoglobulin-like receptors (KIRs) found on their surface. The KIRs are classified as either activating or inhibitory, regarding the effect they produce on NK cells upon interaction with corresponding ligand. Since KIR genes exhibit extensive polymorphism and individuals differ in both the number and kind (activating vs. inhibitory) of KIR genes, it is hypothesized that the KIR gene content might influence the pregnancy outcome. AIM: The aim of this pilot study is to analyze the frequency of different KIR genes in women with infertility problems, and compare them to healthy women. MATERIAL AND METHODS: Total of 122 healthy women (Control) and 25 women with reproductive problems (MISSC) participated in this study. After signing of written consent DNA was isolated from peripheral blood using phenol/chloroform method. The genotyping of 16 KIR genes was performed using commercially available kit from Dynal Biotech, (Pel-Freez Clinical Systems, Brown Deer, WI, USA), based on SSP method. RESULTS: We found that inhibitory KIR are present in similar observed frequency in both control and patients with MISSC, except KIR2DL5 which was found in lower frequency in patients with MISSC. There are no significant differences of all noninhibitory KIR between control and patients with MISSC. The number of inhibitory KIR genes in patients with MISSC was lover, except for seven inhibitory KIR genes which was almost doubled. The number of noninhibiotry (stimulatory) KIR genes was lower in patients with MISSC, except for those with three KIR genes which were almost four times more frequent. We found significantly bigger percentage of 0.34 – 0.60 activating/inhibitory KIR gene number ratio in the patients with MISSC. CONCLUSION: In conclusion, there are differences in the KIR gene distribution, gene number, and activating/inhibitory KIR gene number ratio between control and Macedonian patients with MISSC. Further analysis of frequencies of corresponding KIR genotypes or in the ratio of activating/inhibiting genes content in two groups are needed.

6
Immunonephelometry and Reverse Hybrydization Genotyping in Diagnosis of Alpha-1-Antitrypsin Deficiency in Macedonians

Authors: Olivija Efinska-Mladenovska, Dejan Trajkov, Aleksandar Petlichkovski, Olgica Sibinovska, Slavica Hristomanova Mitkovska, Mirko Spiroski

Abstract

View in PDF

Number of views: 621

BACKGROUND: With a frequency of 1:1600, the alpha-1-antitrypsin deficiency is one of the most frequent hereditary diseases and can be recessively inherited. AAT deficiency is most often caused by inheritance of the so-called PiZ allele. Inheritance of this allele increases the risk of developing chronic obstructive pulmonary diseases (COPD) and liver disease. AIM: The aim of this study was to present immunonephelometry and reverse hybridization genotyping in diagnosis of alpha-1-antitrypsin deficiency in Republic of Macedonia. MATERIAL AND METHODS: At the Institute of Immunobiology and Human Genetics, part of the Faculty of Medicine in Skopje, in the previous 7 years, total of 361 patients with suspected alpha-1-antitrypsin (AAT) deficiency were referred for analysis of AAT concentration using nephelometry (Dade Behring) and subsequent AAT genotyping of individuals with alpha-1-antytripsin deficiency at protein level, based on reverse hybridization technique. RESULTS: Measurement of AAT concentration (g/l) by nephelometry have shown normal level in the range of 1.37-1.41 g/l (88%), lower than normal AAT levels in the range of 0.70-0.83 g/l (8.03%), and concentration above the normal levels in the range of 2.28-2.4 g/l (3.88%). CONCLUSION: Diagnosis in the case of a suspicion of AAT deficiency is carried out by measuring the alpha-1-antitrypsin level in blood and by genotyping of alpha-1-antytripsin allele.

8
Gene Polymorphisms of 22 Cytokines in Macedonian Children with Hyperimmunoglobulinemia E

Authors: Slavica Hristomanova Mitkovska, Dejan Trajkov, Jelena Mihajlovikj, Mirko Spiroski

Abstract

View in PDF

Number of views: 681

INTRODUCTION: For some time it is known that cytokines and their receptors are encoded by highly polymorphic genes. These polymorphisms can be responsible for differences in the production of cytokines between individuals. Large number of the polymorphisms within the regulatory regions of the cytokine genes is in correlation with the production and there are variations among populations. AIM: The aim of this study was to analyze association between polymorphisms in the IFN-gamma, IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-4Ralpha, IL-6, IL-10, IL-12B, TGF-beta1 and TNF-alpha and hyperimmunoglobulinemia E. MATERIAL AND METHODS: The study included 28 unrelated patients with high IgE levels in serum and the control group consisted of 301 unrelated healthy individuals. Cytokine genotyping was performed with PCR-SSP method. We analyzed the allele frequencies, genotypes, haplotypes and diplotypes of the cytokine genes. The differences were analyzed using 2 test, odds ratio and Confidence Interval. RESULTS: Susceptible association with hyperimmunoglobulinemia E was found for four different cytokine alleles (IL-4 -33/T, TGF-beta1 cdn25/C, IL-1 alpha -889/T and TNF-alpha -238/A), ten different genotypes (IL4 -1098/G:G, IL4 -33/T:T, IL-1 alpha -889/C :T, IFN gamma utr5644/A:T, TGF-beta1 cdn25/C:G, IL-6 -174/G:G, IL-1 beta -511/C:T, IL-10 -1082/A:G, TNF alpha -238/A:G andIL-1 beta +3962/C:T) and five different combinations of haplotypes (IL-4/GTT, IL-4/TCT, IL-6/TCC, TNF-alpha/GA and TGF-beta1/CC). Protective association with hyperimmunoglobulinemia E was found in four cytokine alleles (IL-4 -33/C, TGF-beta1 cdn25/G, IL-1 alpha -889/C and TNF-alpha -238/G), three genotypes (IL-10 -1082/A:A, IL-1 alpha -889/C:C and IL4 -33/C:C) and for only one haplotype (IL-4/GCC). CONCLUSION: Several susceptible and protective associations between cytokine gene polymorphisms and hyperimmunoglobulinemia E were found. However, it is still speculative weather these polymorphisms contribute to susceptibility/protection from hyperimmunoglobulinemia E or they might be in significant linkage disequilibrium with some unknown gene responsible for the disease. It is also possible that different ethnical groups show different association with cytokine polymorphisms.

8
Immunological and Immunogenetic Changes in Children with Autistic Disorder in Republic of Macedonia

Authors: Mirko Spiroski

Abstract

View in PDF

Number of views: 649

AIM: The aim of the study was to present our results about immunological and immunogenetic investigations in children with autistic disorder in Republic of Macedonia. METHODS: Infantile autism was diagnosed by DSM-IV and ICD-10 criteria. Plasma samples were collected from 35 autistic subjects, and their 21 siblings (biological brothers and sisters) who served as healthy controls. Plasma samples were separated by centrifugation and stored at –20C until the determination. Plasma immunoglobulin classes (IgM, IgA, IgG) and subclasses (IgG1, IgG2, IgG3, IgG4) were determined using a nephelometer Analyzer. Specific IgA and IgG antibodies against some food allergens, as well as total IgE have been determined with automated immunofluorescent device with solid phase - UniCAP 100 (AmershamBiosciences). HLA DNA typing of class I genes was performed using a Reverse Line Strip method (RLS), and the Sequencing Based Typing method (SBT) was used for typing of class II genes. RESULTS: Children with autism had significantly higher plasma concentrations of IgG4 (p<0.001) compared to their siblings (healthy brothers or sisters). IgE specific antibodies, as well as plasma concentration of total IgE were statistically significant higher in plasma of participants with autism. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0.001), and healthy brothers and sisters from the fathers and mothers (p < 0.001). Our results showed significantly increased frequencies of HLA-C*03 (OR = 2.74*; 2= 4.68; p = 0.03), and HLA-DRB1*01 (OR = 3.10*; 2= 6.26; p = 0.012) alleles in autistic patients when compared to the controls. CONCLUSION: Children with autism have increased plasma concentration of immunoglobulines. Our results demonstrate an association of HLA-C*03 and HLA-DRB1*01 alleles with Macedonian autistic patients. Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.