Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686-7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype-phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.

Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity.

Hereditary angioedema (HAE) is a rare genetic disorder with variable expressivity even in carriers of the same underlying genetic defect, suggesting other genetic and epigenetic factors participate in modifying HAE severity. Recent knowledge indicates the role of immune cells in several aspects of HAE pathogenesis, which makes monocytes and macrophages candidates to mediate these effects. Here we combined a search for HAE phenotype modifying gene variants with the characterization of selected genes' mRNA levels in monocyte and macrophages in a symptom-free period. While no such gene variant was found to be associated with a more severe or milder disease, patients revealed a higher number of dysregulated genes and their expression profile was significantly altered, which was typically manifested by changes in individual gene expression or by strengthened or weakened relations in mutually co-expressed gene groups, depending on HAE severity. SERPING1 showed decreased expression in HAE-C1INH patients, but this effect was significant only in patients carrying mutations supposedly activating nonsense-mediated decay. Pro-inflammatory CXC chemokine superfamily members CXCL8, 10 and 11 were downregulated, while other genes such as FCGR1A, or long non-coding RNA NEAT1 were upregulated in patients. Co-expression within some gene groups (such as an NF-kappaB function related group) was strengthened in patients with a severe and/or mild course compared to controls. All these findings show that transcript levels in myeloid cells achieve different activation or depression levels in HAE-C1INH patients than in healthy controls and/or based on disease severity and could participate in determining the HAE phenotype.

Subsets of Eosinophils in Asthma, a Challenge for Precise Treatment.

The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term "eosinophils" was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of "LIAR" (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, "sine qua non", for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma.

Allergen immunotherapy in treating allergic eosinophilic asthma.

Currently, the approach to a patient with asthma is in accordance with personalized medicine wherein the decision on the treatment pathway is based on the type of asthmatic inflammation and other comorbidities that accompany asthma. For an allergic asthma patient, allergen immunotherapy (AIT), which has a disease-modifying effect and the potential to prevent further progression of allergic symptoms, is one of the treatment modalities. It is an effective treatment that, unlike pharmacotherapy, modifies the course of allergic respiratory diseases and induces allergen specific immune tolerance that persists for up to several years after treatment cessation. Therapeutic allergens of high quality, efficacy, and safety according to European regulatory authorities are an integral part of the treatment of respiratory allergies. It is a safe treatment option which still remains the only causal immuno¬modulatory therapy for allergic eosinophilic asthma.

Risk Factors for Severe COVID-19 and Hospital Admission in Patients With Inborn Errors of Immunity - Results From a Multicenter Nationwide Study.

Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44-3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.

The use of complementary and alternative medicine by adults with allergies: a Czech national representative survey.

BACKGROUND: The prevalence rates of the use of Complementary and Alternative Medicine (CAM) in allergy patients range from 42% in the United States up to 50% in Europe. In the Czech Republic, no such data exists. Our aim was to examine patterns in CAM use in populations with self-reported allergies in the Czech Republic. METHODS: A cross-sectional survey was conducted. A sample of citizens aged 15 years and older, sex, age, and region-stratified, was randomly selected from the 2014 voter registration lists (n = 8,395,132). Respondents with self-reported allergies were further analyzed. RESULTS: Overall, 93% of the respondents with self-reported allergies reported the use of 1 or more CAM modalities during the past 30 days. Herbal teas, relaxation techniques, a detoxifying diet, dietary supplements (excluding vitamins and minerals), and reflexology were used in respondents with allergies. Females, under age 30, with higher education, higher income, and self-reported poor health, were significantly associated with the use of CAM among respondents with allergies. CONCLUSIONS: The prevalence of CAM use among people with self-reported allergies in the Czech Republic is higher compared to other countries, with determinants of CAM varying across specific CAM categories. More attention to existing use is needed to promote the healthy adoption of CAM by raising awareness of its safe and effective use, both for CAM users as well as for health care providers.

Acquired Angioedema with C1 Inhibitor Deficiency: Occurrence, Clinical Features, and Management: A Nationwide Retrospective Study in the Czech Republic Patients.

INTRODUCTION: Acquired angioedema with C1 inhibitor deficiency (AAE-C1-INH) is rare but a potentially life-threatening disease. There are no official prevalence data, nor approved therapies for this condition. OBJECTIVE: In this study, we aimed to collect and analyze clinical data on patients with AAE-C1-INH in the Czech Republic. METHODS: We have conducted a retrospective analysis of AAE-C1-INH patients from Czech referral centers for the treatment of hereditary angioedema with C1 inhibitor deficiency. The inclusion criteria involved recurrent episodes of angioedema with the first manifestation at or after the age of 40, negative family history of angioedema, and C1 inhibitor function 50% or less. RESULTS: A total of 14 patients (7 males and 7 females) met the inclusion criteria for AAE-C1-INH. The median age of the symptom onset was 59.5 years, and the median diagnosis delay was 1 year. The most common clinical manifestation was facial edema (100%) and upper airway swelling (85.7%). All patients responded to the acute attack treatment with icatibant and plasma-derived or recombinant C1 inhibitor concentrate. Lymphoid malignancy was identified in 9 patients (64%), monoclonal gammopathy of uncertain significance in 3 (21%), and in 1 patient autoimmune disease (ulcerative colitis) was considered causative (7%). We were not able to identify any underlying disease only in 1 patient (7%). In 6 of 7 patients (86%) treated for lymphoma, either a reduction in the frequency of angioedema attacks or both angioedema symptoms' disappearance and complement parameter normalization was observed. CONCLUSIONS: The prevalence of AAE-C1-INH in the Czech Republic is about 1:760,000. This rare condition occurs in approximately 8% of the patients with angioedema with C1 inhibitor deficiency. AAE-C1-INH is strongly associated with lymphoproliferative disorders, and treating these conditions may improve the control of angioedema symptoms.

Sensitization to Molecular Components in 104 Atopic Dermatitis Patients in Relation to Subgroups of Patients Suffering from Bronchial Asthma and Allergic Rhinitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. The progression from AD to bronchial asthma (AB) and allergic rhinitis (AR) is called atopic march. The aim of this study was to evaluate the difference in the sensitization to molecular components in patients suffering from AD in relation to subgroups of patients with AR and AB. MATERIAL AND METHODS: The complete dermatological and allergological examinations were performed. Specific IgE antibodies against 112 molecular components were measured with the multiplex ImmnoCAP ISAC test. RESULTS: Altogether 104 atopic dermatitis patients (50 men, 54 women) at the average age 40.1 years were examined. The sensitization to molecular components was confirmed in 93.3% of patients. The sensitization to components of mites, grasses, trees, animals, moulds, and shrimps was significantly more frequent in patients with severe form of AD and the sensitization to components of grasses, trees, and moulds was significantly higher in subgroup of patients with AB. In subgroup of patients suffering from AR the higher occurrence of pollen-derived and pollen-food derived PR-10 proteins, grasses, mites, and animals was observed also. CONCLUSIONS: We have confirmed the significant differences in the sensitization to molecular components in patients suffering from severe form of AD, and in subgroups of patients suffering from AB and AR. These molecular components may play the important role in the consecutive development of different allergy pathologies called atopic march.

Effect of individual allergen sensitization on omalizumab treatment outcomes in patients with severe allergic asthma determined using data from the Czech Anti-IgE Registry.

BACKGROUND: Omalizumab is an efficient drug for patients with uncontrolled severe allergic asthma (SAA). However, little is known about the differences in omalizumab treatment outcomes among patients with different types of atopic sensitization. Here, we assessed the effect of sensitization to individual allergens or their combinations on the outcomes of anti-IgE therapy in patients with SAA. METHODS: We performed a post hoc analysis of data of subgroups of patients enrolled in the Czech Anti-IgE Registry (CAR). The patients were evaluated at baseline and 16 weeks and 12 months after omalizumab treatment initiation. We analyzed the dependence of primary treatment outcomes [global evaluation of treatment effectiveness (GETE) after 16 weeks of treatment, a reduction in severe exacerbation rate (ER), and an improvement in the asthma control test (ACT) result during 12 months of treatment] and secondary outcomes [a reduction in systemic corticosteroid (SCS) use, an improvement in lung functions, and a fraction of exhaled nitric oxide] of patients with SAA treated with omalizumab for 12 months on sensitization to different perennial aeroallergens. We assessed sensitization to house dust mites, molds, and pets at baseline using skin prick tests and/or specific IgE measurement (semiquantitative evaluation). We compared polysensitized patients (sensitized to all tested allergens) with monosensitized (single positivity) or partially polysensitized patients (combined positivity but not to all allergens). RESULTS: We enrolled 279 patients (58.3% women, mean age 52.9 years). Omalizumab treatment presented an 82.8% response rate (according to GETE). It significantly reduced severe asthma exacerbations and SCS use, and improved the ACT result in 161 responders. We identified a subgroup of responders with distinct sensitization patterns (polysensitization to all tested perennial allergens) with higher odds of being responders (OR = 2.217, p = 0.02) and lower tendency to improve ACT result (OR 0.398, p = 0.023) and reduce ER (OR 0.431, p = 0.034) than non-polysensitized patients. CONCLUSIONS: The clinical benefit of sensitization for patients with SAA receiving omalizumab may be particularly dependent on sensitization pattern. Polysensitized patients showed a higher tendency to be responders (GETE), but a lower tendency to improve the ACT result and reduce ER than non-polysensitized patients.

Evolution of our view on the IgE molecule role in bronchial asthma and the clinical effect of its modulation by omalizumab: Where do we stand today?

Bronchial asthma is a heterogeneous disease whose definition and treatment are based on evidence of variable airway obstruction and airway inflammation. Despite the enormous increase in the amount of information on the pathogenesis of this disease, diagnosis is still an unresolved problem, as we still lack sensitive and specific biomarkers. On the other hand, at the turn of the 20th and 21st century, there was a rapid development of therapeutic modalities based on the principle of biological therapy. The first authorized drug matching these characteristics was omalizumab - a monoclonal antibody directed against immunoglobulin E (IgE). It has been used for the treatment of severe forms of bronchial asthma for more than 15 years, which is a sufficient time to acquire ways of its effective use and to assess whether the treatment with omalizumab has met our expectations. However, we continue to discover new and surprising facts about the effects of omalizumab treatment which leads to widening of therapeutic indications. In this work, a basic overview of the very complex role of the IgE molecule in the organism (with a special emphasis on allergic asthma) is discussed, and the most important practical and clinical consequences resulting from its modulation by targeted therapy with omalizumab are summarized.

Serum periostin levels in asthma patients in relation to omalizumab therapy and presence of chronic rhinosinusitis with nasal polyps.

INTRODUCTION: The serum periostin level is a promising biomarker of type 2- high inflammation pattern of bronchial asthma. It has been proven that serum periostin levels decrease in response to systemic and inhaled corticosteroid (ICS) therapy. However, we have only limited knowledge about changes in serum periostin levels reflecting omalizumab (OMA) treatment and other variables, such as chronic rhinosinusitis with nasal polyps (CRSwNP). AIM: To critically appraise clinically relevant parameters influencing periostin levels in asthma patients. MATERIAL AND METHODS: A pilot, cross-sectional, observational study to assess serum periostin levels of 48 asthma patients (38 treated by conventional therapy comprising ICS and 10 treated by ICS and OMA as an add-on therapy) with respect to asthma clinical traits, comorbidities and to other biomarkers of type 2-high asthma phenotype (total IgE, absolute and relative eosinophil count, eosinophilic cationic protein (ECP) and a fraction of exhaled NO (FeNO)). RESULTS: Serum periostin correlates with total IgE levels (Spearman rho = 0.364, p = 0.025) in a subgroup of conventionally treated patients, and with eosinophil count (Spearman rho = 0.401, p = 0.021) in a subgroup of patients with concurrent CRSwNP. Serum periostin levels were decreased in omalizumab-treated patients in comparison to conventionally treated patients (p = 0.025). This effect was remarkably apparent only if CRSwNP was not present (p = 0.005). Conversely, we measured elevated periostin levels in OMA-treated patients with concurrent CRSwNP (p = 0.017). CONCLUSIONS: Serum periostin production is significantly associated with treatment modality (omalizumab vs. conventional) and presence of CRSwNP. These variables need to be taken into account to interpret periostin levels accurately.

Food Hypersensitivity Reactions to Seafish in Atopic Dermatitis Patients Older than 14 Year of Age - The Evaluation of Association with Other Allergic Diseases and Parameters.

BACKGROUND: Seafood allergy is among one of the common food allergies. Decrease in consumption of omega-3 polyunsaturated fatty acids (PUFAs), prevalent especially in oily fish, has been proposed to contribute to the increased prevalence of allergic diseases. AIM: The aim of this study was to evaluate, in atopic dermatitis (AD) patients, the relation between the occurrence of food hypersensitivity reaction (FHR) to seafish and the occurrence of other atopic diseases and parameters. METHODS: Complete dermatological and allergological examination was performed in patients included in the study; 332 patients were examined, with the average age 26.8 years (SD 9.2 years). RESULTS: The FHR to seafish was confirmed in 11% of patients. Patients suffering from FHR to seafish suffered significantly more from sensitization to fungi (in 46%), from reactions to celery (in 34%), and from persistent eczematic lesions (in 82%). CONCLUSION: FHRs to seafish in AD patients are associated with persistent eczematic lesions and with the higher occurrence of sensitization to fungi and reactions to celery. The occurrence of bronchial asthma, rhinitis, positive family history, and onset of AD under 5 years of age is higher in patients with reactions to seafish, but the difference is not statistically significant.

The Occurrence of Food Hypersensitivity Reactions and the Relation to the Sensitization to Grass and Trees in Atopic Dermatitis Patients 14 Years of Age and Older.

BACKGROUND: Although epidemiologic data are scarce, there is no doubt that the increase in pollen allergies is going to be followed by an increase in the so-called pollen-related food allergies. The aim of this study was the evaluation of the food hypersensitivity reactions in atopic dermatitis patients and the relation to the sensitization to grass and trees. METHODS: The complete dermatological and allergological examinations were performed in all included patients; the occurrence of food hypersensitivity reactions was recorded and the sensitization to inhalant allergens (grass and trees) was examined (skin prick test, and specific IgE). The statistical evaluation of the relation between the sensitization to these inhalant allergens and the occurrence of food hypersensitivity reactions was performed. RESULTS: A total of 321 patients were included, with an average age of 26.7 years (±9.2 years) and with an average SCORAD of 33.2 (±13.3) points. The significant relation was recorded between the patients suffering from sensitization to grass and the reactions to peanuts, celery and walnuts; another significant relation was demonstrated between the patients suffering from sensitization to trees and reactions to apple, peanuts, and walnuts. In patients suffering from sensitization to grass and trees, the occurrence of food hypersensitivity reactions to tomatoes, kiwi, spices, oranges, capsicum, tangerines, and carrot was higher also, but the relation was not significant. CONCLUSION: The significant relation was found between the reactions to peanuts and walnuts and sensitization to grass and trees, another significant relation was found between the sensitization to grass and celery and between the sensitization to trees and apple.

Anaphylactic symptoms and anaphylactic shock.

Anaphylactic symptoms and anaphylactic shock are serious, rapidly developing and potentially fatal systemic reactions occurring after contact with the trigger, followed by release of a number of substances that affect vascular permeability, smooth muscle tone of blood vessels and bronchi with activation of the systemic inflammatory cascade. From a pathophysiological point of view, it can be an IgE-mediated immune response followed by massive release of biologically active mediators from mast cells and basophils (IgE dependent). If the mastocyt/basophil is degranulated via a direct IgE-free pathway, it is non-allergic (non-IgE dependent, anaphylactoid anaphylaxis). The diagnosis of anaphylaxis is determined on the basis of clinical criteria, taking into account the need to initiate therapy in a life-threatening condition without delay. Adrenaline is the first-line drug in the treatment of anaphylaxis and there is no contraindication to its use. Early provision of venous intake is essential for the patient to develop hypotension.

Evaluation of Peripheral Blood Eosinophilia in Adolescent and Adult Patients Suffering from Atopic Dermatitis and the Relation to the Occurrence of Allergy to Aeroallergens.

BACKGROUND: Eosinophils play an important pathogenic role in atopic dermatitis (AD), but its exact function remains to be determined. AIMS AND OBJECTIVES: The aim of this study was to correlate the eosinophil count with the manifestations such as asthma bronchiale, rhinitis, level of total IgE, sensitization to mites, animal dander, bird feather, dust, mixture of grass, mixture of trees, mixture of fungi, duration of lesions (persistent or occasional during last year), family history about atopy, and onset of AD (under or above 5 year of age). MATERIALS AND METHODS: Two hundred and seventy-two patients suffering from AD at the age of 14 year or older were examined - 100 men and 172 women with the average age of 26.7±9.5 years and with the average SCORAD index of 32.9±14.1. Complete dermatological and allergological examinations were performed in all patients with the evaluation of monitored manifestations. Mann-Whitney test for difference in medians was used for statistical evaluation. RESULTS: The count of eosinophils in peripheral blood was significantly higher in patients with total IgE ≥200 IU/ml, with sensitization to dust, with persistent eczematous lesions and in patients with the onset of AD under 5 year of age. The count of eosinophils above 5% was recorded as well in patients suffering from asthma bronchiale, rhinitis, sensitization to mites, and in patients with positive family history about atopy, but the difference was not significant. On the other hand, the count of eosinophils was under 5% in patients with sensitization to animal dander, bird feather, mixture of grass and trees. CONCLUSION: Our results demonstrated the difference in the count of eosinophils in peripheral blood according to different manifestations in patients suffering from AD.

Small, Prospective, Observational, Pilot Study in Patients with Severe Asthma after Discontinuation of Omalizumab Treatment.

PURPOSE: Omalizumab has demonstrated clinical efficacy in severe allergic asthma by reducing exacerbation rates and increasing quality of life. However, data concerning its sustained effect after treatment discontinuation are still needed. METHODS: This analysis was an observational pilot study (simple within-subjects design) of 12 patients experiencing severe asthma, treated with omalizumab, for 1 year after treatment discontinuation. We prospectively analyzed clinical measurements (pulmonary functions, inhaled corticosteroid [ICS] doses, Asthma Control Test [ACT] scores, skin prick test [SPT] positivity, fraction of exhaled nitric oxide, and exacerbation rates) and laboratory test results (eosinophils and total immunoglobulin E levels) at the time of discontinuation and 6 and 12 months thereafter. Baseline data (before the treatment period; range, 11-61 months) were collected retrospectively. The treatment effect until discontinuation was calculated. To determine its persistence, repeated measures were compared with baseline levels and analyzed by using a general linear model for repeated measures or the Friedman ANOVA, and χ2 tests in case of normality assumption violation or frequencies. Post hoc analysis was applied by using a simple or repeated contrasts analysis or Wilcoxon signed rank test with Bonferroni correction. FINDINGS: We proved a significant reduction in ICS doses and SPT reactivity and an increase in ACT score during the retrospective treatment phase. Moreover, persistence of these statistically significant effects was recorded 6 months after treatment discontinuation. ACT score and ICS doses (but not SPT reactivity) remained improved for 12 months after discontinuation of omalizumab treatment. IMPLICATIONS: Omalizumab treatment exhibited sustained treatment benefit after its discontinuation for patients experiencing severe allergic asthma.

Treatment of Hereditary Angioedema Attacks with Icatibant and Recombinant C1 Inhibitor During Pregnancy.

PURPOSE: Hereditary angioedema (HAE) is a rare disease caused by a C1 inhibitor (C1-INH) deficit. Clinically, HAE is manifested by repeated episodes of localized subcutaneous or submucosal oedema attacks. Managing HAE patients in pregnancy is challenging, since there are only limited data on the safety and efficacy of various therapeutic approaches. METHODS: We present our clinical experience treating acute HAE attacks during pregnancy in six consecutive patients. RESULTS: During the pregnancies, 79 HAE attacks occurred. The most frequent were abdominal 53 (67.1%) followed by peripheral 21 (26.6%), facial 10 (12.7%), and laryngeal 10 (12.7%) oedemas; 13 (16.5%) attacks were combined. Fifty (63.3%) attacks were treated with recombinant human C1-INH (rhC1-INH); 17 (21.5%) with plasma-derived, pasteurized, nanofiltered C1-INH (pnfC1-INH); 13 (16.5%) with icatibant; and 1 (1.3%) with plasma-derived, nanofiltered C1-INH (nfC1-INH). Treatment had to be repeated in 5 attacks (6.3%). All six deliveries (one caesarean section and five spontaneous vaginal deliveries) were complication free. All pregnancies went to the full term and the patients delivered healthy babies with a birth weight ranging from 2850 to 3690 g. No congenital abnormalities were detected in the neonates. No abortions occurred. CONCLUSIONS: Our results show good C1-INH or icatibant treatment efficacy for HAE attacks in pregnancy. The treatment by the first drug used was effective in 93.7% of all attacks. In 6.3% of attacks, a second treatment had to be used. No adverse effects were observed.

[Secondary humoral immunodeficiency in patiens with systemic lupus erythematosus]. / Sekundární humorální imunodeficience u nemocných se systémovým lupus erythematodes.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystem disease. The aim of our study was to clarify the frequency of decreased serum immunoglobulin levels in SLE patients. There were evaluated 799 results of serum immunoglobulin levels gained from 157 patients fulfilling revised ACR criteria in the retrospective study. RESULTS: The immunoglobulin levels under the normal range were found in 29/157 (18.5 %) patients. The most frequent was isolated reduction of IgG 12/157 (7.6 %), two persons fulfilled criteria for selective IgA deficiency, and one case possible diagnosis of common variable immunodeficiency (CVID). Additionally we report two cases of SLE patients complicated by severe hypogammaglobulinaemia and infectious complications with necessity of long-term immunoglobulin substitution therapy. The diagnosis of CVID is highly probable in the first case. The second case presents sever drug-induced hypogammaglobulinaemia. This female with lymphoma history and multiorgan impairment due to acute SLE was treated with rituximab after convention therapy failure. CONCLUSION: Humoral immunodeficiency may occur in SLE patients. The monitoring of serum immunoglobulin levels could be a routine in these patients. The CVID diagnosis is possible in patients suffering from recurrent sinopulmonary infections, especially in combination with absence of lupus activity. Rituximab therapy could cause long-term suppression of B lymphocytes with secondary humoral deficiency requiring immunoglobulin substitution therapy.

Pregnancy Outcome in Patients with Common Variable Immunodeficiency.

PURPOSE: The aim of our retrospective study was to clarify fertility, pregnancy complications and outcomes in common variable immunodeficiency (CVID) females. METHODS: Retrospective data were obtained from three Czech referral centres. The data were compared with data obtained from the Czech National Registry of Reproduction Health. RESULTS: Our cohort of patients comprised 54 women with 115 pregnancies; 88 pregnancies in 50 females were finished with live births (77 %). In only 8 women (15%) was the diagnosis of CVID established before the first pregnancy. Replacement immunoglobulin therapy was performed in 10 patients without any moderate or severe adverse effects. Compared with the Czech population, the CVID patients suffered significantly more frequently from the threat of preterm labour (p < 0.0001), vaginal bleeding (p = 0.0001), eclampsia/preeclampsia (p = 0.009) and a higher number of stillbirths (p < 0.0001). Furthermore, the frequency of babies with low birth weight (less than 2500 g) born to the CVID patients was increased compared with the normal population (p < 0.0001). Serum IgG, IgA and IgM determination was done in 57 children of 50 mothers showing 13 cases of IgA deficiency (23%). There was no significant difference among the non-symptomatic, symptomatic untreated and symptomatic treated females in any of the determined gynaecological complications. The number of unsuccessful pregnancies was higher in the symptomatic untreated women. CONCLUSIONS: Fertility in CVID patients is not decreased, and their pregnancies could be considered more risky compared with those of the general population.