The Role of Intravenous Immunoglobulin Preparations in the Treatment of Systemic Sclerosis

Scleroderma is progressive autoimmune disease associated with severe disability. The major underlying pathological process in scleroderma is progressive development of fibrous tissue and obliteration of the microvasculature. Currently, there are no medical products for the treatment of scleroderma that provide both sufficient immunosuppression and low-risk side safety profile with negligible side effects. There are a large number of experimental data showing that intravenous immunoglobulin (IVIG) has multiple clinical and morphological effects. On the other hand, some authors report good effect of intravenous immune globulins in patients with scleroderma. The less frequent side effects of IVIG in doses below or equal to 2 g/kg/month divided in 5 consecutive days make IVIG a promising treatment of choice in scleroderma

Thromboembolism in Renal Diseases

Patients with renal diseases are prone to both thrombosis and bleeding, as they have profound changes in all three classic components of coagulation, defined approximately 150 years ago by Virchow: blood flow, vessel wall (endothelial injury), and coagulation properties of the blood (e.g., coagulation and fibrinolytic systems and platelets). The prothrombotic state in chronic kidney disease (CKD), glomerular diseases (including systemic lupus and vasculitis), and some less frequent conditions (idiopathic retroperitoneal fibrosis, antiphospholipid syndrome, hemolytic‐uremic syndrome, etc.) is associated with vascular endothelial damage, increase in certain coagulation and antifibrinolytic factors, decrease in anticoagulation proteins, dyslipidemia, hypoalbuminemia, changes in platelet membranes, hemo‐ and peritoneal dialysis and heparin treatment, increased microRNAs and circulating microparticles, antiphospholipid antibodies, nephrotic syndrome, anemia with high platelet count, and so on. Nevertheless, the same patients have substantially increased risk of bleeding due to platelet dysfunction and intake of certain medications (antiaggregants, heparin and low‐molecular weight heparins, and anemia). The aim of this review is to present the main thrombo‐embolic risk factors in a wide variety of patients with renal diseases, including chronic glomerulonephritis (primary and secondary), chronic renal disease, and idiopathic retroperitoneal fibrosis. We have evaluated the risk factors for arterial and venous thromboses in a wide variety of renal patients with both glomerular and non‐glomerular diseases, including the presence of nephrotic syndrome, inborn and acquired coagulation defects (i.e., factor V Leiden, MTHFR gene mutation, 20210 prothrombin gene mutation, and antiphospholipid antibodies), corticosteroid treatment, and dyslipidemia. We are describing the results of these investigations and suggesting prophylactic anticoagulant strategies in such patients. Multiple risk factors influence the coagulation system in renal disease leading to both hypercoagulation and hemorrhagic diathesis. Therefore, renal patients should be thoroughly investigated for coagulation abnormalities, especially if pathogenic (i.e., corticosteroid and immunosuppressive) and anticoagulation treatment is to be initiated. Moreover, the doses of anticoagulant/antiaggregant and hemostatic medications should be considered carefully, having in mind the underlying diseases and risk factors, renal function, and concomitant treatment

Viral load and lymphocyte subpopulations in newly diagnosed patients with chronic Hepatitis B

INTRODUCTION: The immune response against Hepatitis B virus (HBV) represents a key factor for infection outcome. However, the relation between viral replication and host immune reactivity is still a matter of investigation. AIM: To investigate whether the cellular immune response of newly diagnosed treatment naïve chronic hepatitis B (CHB) patients may be influenced by the replicative status of HBV.MATERIALS AND METHODS: A total of 45 (17 female and 28 male) newly diagnosed untreated CHB patients aged 42.48±13.19 years (19÷71 years) were enrolled in this study. The patients were divided in two groups according to the viral load: >0÷≤104 copies/ml (n=25) and >10 4÷<108 copies/ml (n=17). Flowcytometric immunophenotyping was performed for evaluation of the cellular immunity. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction.RESULTS: Similar alterations were observed in both patients` groups in comparison with healthy controls which could be summarized as follows: decreased total T cells (CD3+) due to low helper-inducer (CD3+CD4+) and suppressor-cytotoxic (CD3+CD8+) subpopulations; reduced effector cytotoxic (CD8+CD11b-; CD8+CD28+) and activated (CD3+HLA-DR+, CD8+CD38+) T-cell subsets; increased CD57+CD8- cells; elevated percentage of B lymphocytes. No significant differences in the studied immune parameters were detected between both patients` groups except the significantly elevated CD4/CD8 ratio in individuals with higher in comparison to those with lower HBV DNA levels.CONCLUSION: Alterations in the cellular immune repertoire of CHB patients were observed resulting mainly in significantly decreased T-cell subpopulations, particularly those with effector cell immune phenotype regardless of the viral load

Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients

OBJECTIVES: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. METHODS: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years. RESULTS: 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%. CONCLUSIONS: Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications

Atopic Status in Children with Asthma and Respiratory Allergies&mdash;Comparative Analysis of Total IgE, ImmunoCAP Phadiatop/fx5 and Euroimmun Pediatric Immunoblot

Introduction: An atopic status assessment (skin prick test or specific immunoglobulin (sIgE)) in asthmatic children is considered a milestone in identifying potential risk factors and triggers provoking loss of asthma control and asthma exacerbation. Objective: The study aims to perform a comparative analysis of different laboratory methods for a serological assessment of an atopic status in asthma and respiratory allergies in children. Material and methods: A total of 86 children were included, all of whom were diagnosed with bronchial asthma, aged from 5 to 17 years and screened for total IgE level using enzyme-linked immunosorbent assay (ELISA). In 48 randomly selected children, we performed a semi-quantitative serological in vitro assessment of the specific IgE antibodies against food and aeroallergen, using two different laboratory methods&mdash;Euroimmun Immunoblot and ImmunoCAP (Phadiatop/fx5). Results: In 70% of the children with a history of allergies, and 65.3% without clinically manifested allergies, multiscreen test ImmunoCAP Phadiatop/fx5 showed positivity and confirmed atopy. Our results showed a significant moderate to strong correlation between multiscreen ImmunoCAP Phadiatop/fx5, and Euroimmun specific IgE titers against aero-allergens&mdash;cats, mites, tree mix and food allergens&mdash;soy, wheat (&#1088; = 0.006), rice, &#1088; = 0.090), apple &#1088; = 0.007) and peanut. A sensitivity of 63% and specificity of 73.5% was observed for EUROIMMUN Pediatric (food allergens, IgE titer &gt; 1) compared with the gold standard ImmunoCap/fx5. The mean value of total IgE is significantly higher in children with asthma and concomitant with allergic rhinitis compared to those without allergic rhinitis (mean 202.52 U/mL, IQR 102.50 (24.20&ndash;363.95) vs. 316.68, IQR 261.00 (109.20&ndash;552.50), p = 0.005). Conclusion: Establishing the spectrum of the most common respiratory and food allergens is an essential factor for maintaining asthma control, both through a strategy to avoid allergen exposure and by developing a recommendation plan. The immunoblotting technique is easily applicable in daily clinical and laboratory practice. It is also a cost-effective and reliable alternative to the &ldquo;gold standard&rdquo; ImmunoCAP Phadiatop/fx5 in diagnosing atopy in children

The Coexistence of Systemic Lupus Erythematosus and Thyrotoxicosis: The Diagnostic Value of Antihistone Antibodies

We report four female patients with Graves' disease with positive ANA antibodies and possibility for development of systemic lupus erythematosus. All four patients have been treated with antithyroid drugs. SLE symptoms have appeared from 4 to 12 months after the beginning of therapy with methysol in two of them. The third patient had no symptoms for SLE, but her ANA, anti-DNA, and antihistone antibodies had been positive at the time of the onset of thyrotoxicosis. The fourth patient had alopecia areata with positive ANA and antihistone antibodies

Role of the Promoter Polymorphism IL-6 −174G/C in Dermatomyositis and Systemic Lupus Erythematosus

The promoter polymorphism −174G/C within the interleukin-6 gene (IL-6) has been reported to have a functional importance through the modulation of IL-6 gene expression in vitro and in vivo. IL-6 is thought to play an important role in autoimmune diseases and the effect of its receptor inhibitor—tocilizumab—has been recently studied. The aim of this case-control study was to investigate the association between the interleukin-6 −174G/C single nucleotide polymorphism and the susceptibility to dermatomyositis (DM) and systemic lupus erythematosus (SLE) in Bulgarian patients. Altogether, 87 patients—52 with SLE and 35 with DM—as well as 80 unrelated healthy controls were included in this study. All of them were analyzed by restriction fragment length polymorphism analysis (RFLP). The GG genotype and the G allele appeared to be associated with SLE, especially in women. None of the genotypes showed an association with DM. However, the G allele appeared to be associated with muscle weakness and it is a risk factor for elevated muscle enzymes. Our results indicate that IL-6 −174G/C polymorphism might be associated with the susceptibility to SLE especially in women. Although it is not associated with DM, it seems that IL-6 −174G/C polymorphism could modulate some clinical features in the autoimmune myopathies

On Two Cases with Autosomal Dominant Hyper IgE Syndrome: Importance of Immunological Parameters for Clinical Course and Follow-Up

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare disease described in 1966. It is characterized by severe dermatitis, a peculiar face, frequent infections, extremely high levels of serum IgE and eosinophilia, all resulting from a defect in the STAT3 gene. A variety of mutations in the SH2 and DNA-binding domain have been described, and several studies have searched for associations between the severity of the clinical symptoms, laboratory findings, and the type of genetic alteration. We present two children with AD-HIES–a girl with the most common STAT3 mutation (R382W) and a boy with a rare variant (G617E) in the same gene, previously reported in only one other patient. Herein, we discuss the clinical and immunological findings in our patients, focusing on their importance on disease course and management