Frequent Occurrence of Alzheimer Disease in Patients With IgE-mediated Allergies.

Alzheimer disease and allergic diseases are common health problems. The aim of the study was to check the hypothesis that older patients with IgE-mediated allergies have a higher prevalence of Alzheimer disease. It was a retrospective, multicenter cohort observation. In total, 7129 people were examined, including 3566 women and 2558 men (mean 64.9±6.9 y). The diagnosis of Alzheimer disease is based on the ICD-10 code and appropriate medical documentation. The proportion of patients with confirmed Alzheimer disease in the group of patients with diagnosed allergy compared to the group of those without allergy was as follows: 13.9% (168) versus 8.2% (484) with P=0.001. There was a positive correlation between the presence of Alzheimer disease and high serum total IgE, eosinophilia, and asthma or the presence of atopic polymorphic disease (P<0.05). IgE-dependent allergic diseases, in particular allergic asthma, and the presence of high serum IgE levels may favor the development of Alzheimer disease.

Evaluation of the Levels of Selected Cytokines and Their Possible Influence on the Development of Cardiovascular and Pulmonary Complications in Patients after COVID-19.

Background and Objectives: The aim of this study was to evaluate the levels of selected cytokines and their possible influence on the development of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19. Materials and methods: The study included 76 randomly selected patients from the SILCOVID-19 database. The median time from symptom onset to the study visit was 102 (86-118) days. The median age of the study group was 53 (44-60) years. Assays of a panel of 30 cytokines were carried out in the serum of patients on a Luminex100 platform using the Milliplex MAP kit from Merck KGaA Germany. Results: There were no statistically significant differences in most of the cytokines analyzed between patients with confirmed or excluded lung lesions or cardiac abnormalities. Additionally, no statistically significant differences in cytokine concentrations according to gender, age, comorbidity of diabetes, renal disease, hypertension, increased risk of thrombotic disease, or psychological disorders were demonstrated. There were high concentrations of cytokines such as platelet-derived growth actor-AA (PDGF-AA), monocyte chemoattractant protein-1 (MCP-1), monokine-induced gamma interferon (MIG), and vascular endothelial growth factor-A (VEGF-A). Conclusions: No direct impact of the dependencies between a panel of cytokines and the incidence of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19 was demonstrated. The demonstration of high levels of certain cytokines (PDGF-AA, VEGF, MIG, and IP10) that are of significance in the development of many lung diseases, as well as cytokines (MCP-1) that influence the aetiopathogenesis of cardiovascular diseases seems to be highly concerning in COVID-19 survivors. This group of patients should receive further monitoring of these cytokine levels and diagnostic imaging in order to detect more severe abnormalities as early as possible and administer appropriate therapy.

Acquired Angioedema in Selected Neoplastic Diseases.

Background and Objectives. Acquired angioedema is a relatively common revelation accompanying some diseases such as autoimmune or cancer. The study aimed to assess the incidence of one subtype of angioedema-C1-INH-AAE (acquired angioedema with C1 inhibitor deficiency). Material and methods. The study was retrospective and based on 1 312 patients with a final diagnosis of breast cancer, colorectal cancer, or lung cancer: 723 women and 589 men with a mean age of 58.2 ± 13.5 years. The cancer diagnosis according to the ICD (International Classification of Diseases)-10 code, medical history including TNM (Tumour, Node, Metastasis) staging, histopathology, and assessment of the occurrence of C1-INH-AAE angioedema were analysed. Results. C1-INH-AAE occurred more often in patients with cancer than in the control group, as follows: 327 (29%) vs. 53 (6%) for p < 0.05. C1-INH-AAEs were observed most often in the group of patients diagnosed with breast cancer compared to colorectal and lung groups: 197 (37%) vs. 108 (26%) vs. 22 (16%) (p < 0.05). A higher incidence of C1-INH-AAE was observed in the early stages of breast cancer. However, there was no relationship between the occurrence of C1-INH-AAE and the BRCA1 (Breast Cancer gene 1)/BRCA2 (Breast Cancer gene 2) mutation or histopathological types of breast cancer. Conclusion. Angioedema type C1-INH-AAE occurs more often in patients with selected neoplastic diseases, especially in the early stages of breast cancer.

Allergen immunotherapy against house dust mites in patients with local allergic rhinitis and asthma.

METHODS: The study was a prospective, double-blind, placebo-controlled trial with patients diagnosed with LAR to HDMs and with concomitant asthma who underwent a 12-month treatment course of SLIT for HDM allergies. Seventeen patients were randomized to SLIT with the use of allergen extracts of D. pteronyssinus and D. farinae (50/50%) in SQ-HDM SLIT tablets and 15 patients were randomized to the placebo group. The total rhinitis score (TRSS), total asthma symptom score (TASS), combined total symptom score (TSS), total medication score (TMS), and FEV1 were analyzed.Results: In the final analysis, 16 patients who received SLIT and 14 who received placebo who completed the study protocol were included. Significant reductions in TRSS, TASS, TSS, and TMS after 12 months of treatment were observed in patients after SLIT (p < 0.05). A significant increase in the mean FEV1 between baseline and after 12 months of therapy was observed in the study, with p = 0.03 in the study group. Conclusion: SLIT can improve nasal and bronchial symptoms and reduce symptomatic treatment in patients with LAR and asthma and with hyperresponsiveness to HDMs.

Differential expression of tumor necrosis factor α, interleukin 1ß, nuclear factor κB in nasal mucosa among chronic rhinosinusitis patients with and without polyps.

INTRODUCTION: The pathogenesis of nasal polyps is still not fully understood. AIM: To analyze the topography and intensity of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2), nitric oxide synthase 2 (NOS-2), and nuclear factor-κB (NF-κB) expressions in eosinophilic and neutrophilic polyps and in normal nasal mucosa. MATERIAL AND METHODS: The study included specimens from 20 patients with eosinophilic polyps (more than 10% of eosinophils in inflammatory infiltrate), 20 individuals with neutrophilic polyps (predominance of neutrophils and less than 10% of eosinophils), and samples of normal nasal mucosa from 10 controls. The expressions of studied proteins in vascular endothelial cells, epithelial, stromal and glandular cells were determined immunohistochemically with specific monoclonal antibodies. RESULTS: Irrespective of the cellular type, the intensity of expressions in eosinophilic and neutrophilic polyps was significantly higher than in the normal mucosa. Eosinophilic polyps were characterized by stronger expressions of TNF-α (in all cellular types), IL-1ß (in endothelial, glandular and epithelial cells), NF-κB (in stromal and epithelial cells), COX-2 (in glandular and stromal cells), and NOS-2 (in endothelial and stromal cells). In contrast, neutrophilic polyps showed significantly stronger expressions of COX-2 (in epithelial and endothelial cells) and NOS-2 (in glandular and epithelial cells). In both phenotypes, the strongest expressions of all studied markers were documented in vascular endothelial cells. CONCLUSIONS: Inflammatory markers are involved in pathogenesis of both eosinophilic and neutrophilic polyps. Endothelial defects can play an important role in the development of nasal polyps.

Refractory chronic spontaneous urticaria and permanent atrial fibrillation associated with dental infection: Mere coincidence or something more to it?

Controversy surrounds the role of dental infection/inflammation in the oral cavity in chronic spontaneous urticaria (CSU) and atrial fibrillation (AF), which is mainly due to scarce literature in this area. Therefore, this case report and review of literature illustrate a possible association between the acute-phase response (APR) and clinical conditions, such as CSU and dental infection/inflammation of oral cavity and AF.We describe a 36-year-old man with an 8-year history of difficult-to-treat, uncontrolled CSU, co-existent with dental infection/inflammatory processes of oral cavity and permanent atrial fibrillation (AF). In the presented case, the most likely triggering or aggravating/maintaining factor of the symptoms was the inflammation/dental infection of the oral cavity because of rapid reduction of the urticarial symptoms, drug doses, and serum CRP levels after the dental therapy. Dental treatment may have a beneficial effect on the systemic inflammatory response, reducing/normalizing the circulating levels of APR markers. APR activation appears to worsen CSU course, early identification and treatment of infectious/inflammatory foci in the oral cavity would form the mainstay of supportive therapy for CU probably through reduction of the systemic inflammatory burden. APR associated with infectious/inflammatory foci in the oral cavity could be taken into account as a predisposing agents to AF.

Specific immunotherapy with mugwort pollen allergoid reduce bradykinin release into the nasal fluid.

INTRODUCTION: A pathomechanism of allergic rhinitis is complex. A neurogenic mechanism seems to play a significant role in this phenomenon. AIM: The evaluation of influence of specific immunotherapy of mugwort pollen allergic patients on the bradykinin concentration in the nasal lavage fluid. MATERIAL AND METHODS: The study included 22 seasonal allergic rhinitis patients. Thirty persons with monovalent allergy to mugwort pollen, confirmed with skin prick tests and allergen-specific immunoglobulin E, underwent a 3-year-long allergen immunotherapy with the mugwort extract (Allergovit, Allergopharma, Germany). The control group was composed of 9 persons with polyvalent sensitivity to pollen, who were treated with pharmacotherapy. Before the allergen-specific immunotherapy (AIT) and in subsequent years before the pollen seasons, a provocation allergen test with the mugwort extract was performed, together with collection of nasal fluids, where bradykinin concentration was determined according to Proud method. RESULTS: There were similar levels of bradykinin in both groups at baseline prior to therapy (AIT group: 584.0 ±87.2 vs. controls 606.3 ±106.5 pg/ml) and changes after allergen challenge 1112.4 ±334.8 vs. 1013.3 ±305.9 pg/ml as well. The bradykinin concentration in nasal lavage fluid after mugwort challenge in 1 year was lower in the AIT group (824.1 ±184.2 pg/ml vs. 1000.4 ±411.5 pg/l; p < 005) with a further significant decrease after the 2(nd) and 3(rd) year of specific immunotherapy. Significant reduction of symptoms and medications use was observed in hyposensitized patients. CONCLUSIONS: A decreased level of bradykinin as a result of AIT suggests that some of the symptomatic benefits of AIT may be related to the reduced release of bradykinin into nasal secretions. These values correlate with clinical improvement within the course of treatment.

Analysis of selected allergic reactions among psoriatic patients.

INTRODUCTION: Psoriasis is a chronic and recurrent inflammatory skin disease. The aetiology is still unknown in spite of numerous scientific researches. There is very little evidence which does not provide enough knowledge about allergic reactions in psoriatic patients. Based on the fact that the epidermal barrier damage allows different allergen types to penetrate into deep layers of epidermis and skin, we can assume that it may lead to immunological reactions. AIM: To investigate the allergic reaction indicators and hypersensitivity assessment about contact, inhalant and food allergens. The results were analysed with regard to clinical disease indicators and progression stage of dermal lesions. MATERIAL AND METHODS: Eighty patients with psoriasis were examined. The concentration of total IgE antibodies and allergen specific IgE antibodies (asIgE) were analysed. Standard epidermal tests and atopy patch tests were performed. All the patients were estimated for their dermatological condition based on the PASI scale. The control group consisted of 50 patients without psoriasis and allergic history. RESULTS: Significantly higher concentration of total E immunoglobulin has been stated in the patients with psoriasis. Higher concentrations of specific allergic IgE antibodies were more often observed in the examined group but the most frequently observed values were present in 1-3 class. The most common airborne allergens were birch, artemisia, timothy and rye pollens. There have not been any significant statistical differences in the case of positive epidermal test results. CONCLUSIONS: There is slightly expressed hypersensitivity in psoriatic patients. This hypersensitivity degree correlates with the intensification of symptoms.

Local allergic rhinitis in elderly patients.

BACKGROUND: Local allergic rhinitis (LAR) is characterized by the production of specific IgE in the nasal mucosa and a positive response to a nasal provocation test in the absence of atopy by conventional measurements. There is no information about LAR in elderly people, just as there is little information about allergic rhinitis (AR) in this age group. OBJECTIVE: To investigate the prevalence of LAR, AR, and non-AR in elderly patients with rhinitis. METHODS: In 219 patients with a mean (SD) age of 65.81 (5.88), skin prick tests, serum total specific IgE, and nasal provocation tests against common aeroallergens were performed. In addition, nasal specific IgE was measured in the nasal lavage at baseline and after provocation. For monitoring nasal symptoms, a visual analog scale was used. RESULTS: Of the 219 patients, 46 (21.0%) had LAR, 88 (40.2%) had AR, and 85 (38.8%) were diagnosed as having non-AR. Dermatophagoides pteronyssinus was the main sensitizing aeroallergen in patients with LAR (29 patients [63.0%]) and with AR (48 patients [56.4%]). No significant differences were found between the visual analog scale score and the type of AR (local or nonlocal) and the types of allergens. Clinical responses during the nasal provocation test were associated with significant increases in nasal IgE (Spearman correlation test, R = 0.89, P < .05). Polysensitization was more predominant in patients with AR than in those with LAR (P < .05). CONCLUSION: The results indicate that LAR and AR are common in elderly patients. However, in this age group, these conditions are often underdiagnosed.

Circulating concentration of markers of angiogenic activity in patients with sarcoidosis and idiopathic pulmonary fibrosis.

BACKGROUND: Angiogenesis is an important process involved in the pathogenesis of diffuse parenchymal lung diseases. The aim of the study was to compare the angiogenic profile of patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF) based on analysis of circulating factors. METHODS: Serum concentrations of angiopoietin-2 (Ang-2), follistatin, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-8 (IL-8), platelet derived growth factor-BB (PDGF-BB), platelet endothelial cellular adhesion molecule-1 (PECAM-1) and vascular endothelial growth factors (VEGF) were measured in the patients and the healthy subjects. RESULTS: Serum concentrations of G-CSF, follistatin, PECAM-1 and IL-8 were significantly higher in the IPF patients in comparison with the control group and the sarcoid patients. PDGF-BB concentrations were also significantly higher in serum of IPF patients than in sarcoid patients, but not than in the controls. In contrast, Ang-2 and VEGF concentrations did not differ significantly between the three groups. In the sarcoid patients, irrespective of the disease activity or the radiological stage, serum concentrations of these cytokines were similar to the control group. CONCLUSIONS: These results indicate that differences may exist in angiogenic activity between patients with parenchymal lung diseases. In contrast to sarcoidosis, IPF is characterized by a higher serum concentration of different molecules involved in the angiogenic processes .

Frequency of IgE-dependent hypersensitivity to moulds in patients with chronic rhinosinusitis with polyps.

INTRODUCTION: The complicated etiology of chronic sinusitis with polyps and frequent allergy to mould is established. AIM: We aimed to investigate the frequency of the IgE-dependent hypersensitivity in this group of patients and prove the need of surgery in allergic chronic rhinosinusitis patients. MATERIAL AND METHODS: Forty-two patients (19 females, 23 males) aged 34-73 years (55 ±12.6 years), with chronic sinusitis with polyps were included into the study. Functional endoscopic sinus surgery, laryngological examination, sinus computed tomography scans, and smear from maxillary sinus for microbiological examination were done in all patients. Skin prick tests with common perennial and seasonal inhalant allergens, tIgE and sIgE against moulds were required. RESULTS: Thirty-two of 42 patients (71.4%) were allergic to at least one inhalant allergen. A mean concentration of total IgE was 241.2 ±186.3 kU/l (35.0-708.0 kU/l) and was lower in patients with fungal culture found in sinus mucin than in patients without fungal presence 75.1 ±54.6 kU/l vs. 284.3 ±204.1 kU/l. We found no difference in the number of positive skin prick tests in a group with and without fungal culture. None of patients with fungal culture found in sinuses presented a detectable level of mold sIgE. All patients with fungal vegetation in sinuses required at least two polypectomy procedures. CONCLUSIONS: The total IgE concentration was significantly lower in patients with fungal presence in sinuses. Nasal polyps occurred more frequently in patients with fungal presence in sinuses.

The Occurrence of Atopy in Patients with Isolated Spontaneous Mast Cell (or Nonallergic) Angioedema.

BACKGROUND: Isolated mast cell angioedema (MC-AE) can be divided into allergic and nonallergic (spontaneous) forms. The former is often associated with food, Hymenoptera venoms or drug allergies. This study aimed to evaluate the relationship between the occurrence of atopic diseases and the risk of angioedema. METHODS: A retrospective study analyzed 304 patients with confirmed MC-AE and 1066 controls. All were analyzed for allergic asthma (AA), atopic dermatitis (AD) and allergic rhinitis (AR) based on ICD-10 codes. In addition, total IgE and peripheral eosinophilia were calculated. RESULTS: The analyzed atopic diseases were more frequent in the group of patients diagnosed with MC-AE than in the controls: 78 (25.7%) vs. 173 (16.2%) for p < 0.01. Patients diagnosed with AD had a higher risk of MC-AE (hazard ratio (HR) = 1.48,) similar to those diagnosed with AR (HR = 1.51). However, in patients with two or three atopic comorbidities, the risk increased significantly to HR = 2.45 or HR = 4.1, respectively. There was a positive correlation between the serum total IgE concentration or eosinophilia and the risk of angioedema (p < 0.01). CONCLUSION: Patients with MC-AE had a more frequent occurrence of atopic diseases associated with inhalant allergies. This risk increased in patients with IgE-mediated polymorphic disease.

The effect of pimecrolimus on expression of genes associated with skin barrier dysfunction in atopic dermatitis skin lesions.

The mechanism of action of pimecrolimus (PIM) on atopic lesions is still under consideration. Thus far, we have evidence of its anti-inflammatory and immunomodulatory activity, and recent papers focus on its effect on epidermal barrier function. This study analysed changes in the expression of genes associated with skin barrier dysfunction in atopic dermatitis (AD) skin lesions after 2 weeks of exposure to PIM 1% cream. A real-time quantitative PCR analysis of selected epidermal differentiation complex genes and three alternative pathway keratins was performed in skin biopsies from 11 individuals with AD before and after PIM exposure. The real-time quantitative PCR analysis was compared to non-lesional skin in the same patients. Involucrin, a small proline-rich region (SPRR) 2C gene, and alternative pathway keratin 16 showed significant over-expression in lesional skin followed by significant decrease after PIM therapy. The SPRR1A gene, S100A9, and keratin 6A were also increased; however, the decrease after PIM treatment was not significant. The changes in S100 A2, A7 and A8 followed a similar course with borderline significance. SPRR4 had a significant decrease in expression in lesional versus non-lesional skin, which persisted after PIM treatment. No significant changes were detected in mRNA expression levels of filaggrin and loricrin. Our results suggest that PIM can be effective in restoring the epidermal barrier in patients with AD at least in part by its impact on expression of genes, which are important for the normal barrier function of skin.

[The quality of voice in coal-miners after burn/inhalation injury due to methane explosion]. / Jakosc glosu u górników po urazie inhalacyjnym górnych dróg oddechowych w wyniku wybuchu metanu.

The job as a coal-miner exposes to the greatest risk. One of the most dangerous health hazard is a burn/inhalation injury during the methane explosion. The victims undergo physical trauma, effect of high temperature and inhalation of toxic gases and products of incomplete combustion, As a result of inhalation injury both, upper and lower airways are affected. The aim of the study was to analyse the relationship between burn/inhalation injury and quality of voice in affected coal-miners. A group of 23 patients (men) in age from 28 to 59 (mean 38.5) 3 years after burn/inhalation injury participated in this study. The voice evaluation based on ENT examination, videlaryngostroboscopy, acoustic analysis, MPT parameter and GRBAS analysis was performed. The special control group of coal-miners served as a control. On the basis of the subjective evaluation and the objective acoustic analysis, aerodynamic parameter and videlaryngostroboscopy the worse quality of voice in the group of injured coalminers was shown in comparison to the control group. No substantial correlation between the acoustic parameters, MPT parameter and ventilating rates was found.

Post-COVID­19 complications in hospitalized and nonhospitalized patients: the Silesian database of COVID­19 complications (SILCOV­19).

INTRODUCTION: Due to the extent of the pandemic, high prevalence and severity of complications in the early post­recovery period are expected. OBJECTIVES: This study aimed to compare the scope of early post-COVID­19 complications in patients who had the disease and were or were not hospitalized. PATIENTS AND METHODS: This was a prospective, observational, registry­based cohort study conducted at a tertiary cardiovascular hospital in Silesia, Poland. Interdisciplinary diagnostics, including cardiovascular, pneumatological, respiratory, neurological, and psychiatric tests, was performed during the study visit. All patients completed the study. Two­hundred unselected, adult, white men and women with the symptoms of acute COVID­19 were included, of which 86 patients had the disease but did not require hospitalization. RESULTS: The median (interquartile range) time from symptom onset to the study visit was 107 (87-117) and 105 (79-127) days in nonhospitalized and hospitalized patients, respectively. Lung lesions on high­resolution computed tomography were found in 10 (8.8%) and 33 (39.3%) of nonhospitalized and hospitalized patients, respectively (P <0.01); no lesions were visualized on chest X­ray images. Elevated platelet distribution width was found in more than 70% of the patients in both groups. More than half of the patients had insomnia, regardless of the hospitalization status. CONCLUSIONS: The abnormal platelet parameters, functional and radiological findings in the lungs, and insomnia were the most frequent short­term COVID­19 complications in hospitalized and nonhospitalized patients. Considering the number of patients who have had COVID­19 worldwide, a high burden of the post-COVID­19 complications might be expected.

Successful correction of hyperglycemia is critical for weight loss and a decrease in cardiovascular risk in obese patients.

Weight loss is recommended for obese patients with cardiovascular risk; however, it remains questionable how hyperglycemia affects this process. To address this problem, we aimed to determine the association between weight loss, lipid profile, and body mass parameters in obese normoglycemic and hyperglycemic patients. Obese (body mass index30 kg/m2) normoglycemic and hyperglycemic volunteers were placed on a weight reduction program that included a balanced, low-calorie diet and moderate exercise for 6 months. Participants were assessed for serum glucose, ß-cell functions, insulin resistance, lipid metabolism, lipoprotein profile, and body mass parameters. This weight reduction program fully normalized serum glucose levels only in a subpopulation of patients. These individuals also exhibited a significant reduction in body weight, and significant improvement in serum lipid profile and insulin resistance. In contrast, the patients that remained hyperglycemic were characterized by persistent insulin resistance, increased levels of atherogenic fractions of LDL and HDL lipoproteins, and elevated values of a modified Atherogenic Index of Plasma. Correlation analysis indicated a strong positive association between the modified Atherogenic Index of Plasma with atherogenic lipid profile, insulin resistance, and body mass parameters, indicating its usefulness in clinical studies in obese patients. Overall, our data indicate that successful treatment of hyperglycemia facilitates weight loss and improves the composition of blood lipids, while persisting hyperglycemia negatively affects the weight loss process and maintains an atherogenic lipid profile. Because hyperglycemia predisposes to cardiovascular disorders, its correction should be the primary goal during weight reduction therapy.

Molecular mechanisms of glucocorticoids action: implications for treatment of rhinosinusitis and nasal polyposis.

Intra-nasal glucocorticoids are the most effective drugs available for rhinosinusitis and nasal polyposis treatment. Their effectiveness depends on many factors and not all of them have been well recognized so far. The authors present the basic information on molecular mechanisms of glucocorticoid action, direct and indirect effects of glucocorticoids on transcription of genes encoding inflammatory mediators. They focus on recently proved nongenomic mechanisms which appear quickly, from several seconds to minutes after glucocorticoid administration and discuss clinical implications resulting from this knowledge. Discovery of nongenomic glucocorticoid actions allows for better use of these drugs in clinical practice.

Impact of influenza vaccination on the risk of SARS-CoV-2 infection in a middle-aged group of people.

Aims: An observational study of a retrospective cohort was performed to assess the impact of influenza vaccination (IV) on the risk of SARS-CoV-2 infection in a population of middle-aged people for 8 weeks after IV and compared with an unvaccinated group.Patients and methods: Data from 1098 middle-aged patients (53.7 ± 4.7 years) after IV and 1205 unvaccinated patients (50.1 ± 6.8 years) were analyzed based on medical documentation. The inclusion criteria were age between 40 - 60 years and IV in the period from 1-30 September 2020. The incidence of infection with SARS-CoV-2 was confirmed by PCR and the classification of ICD-10 (U07.1).Results and conclusions: After IV, patients had significantly fewer SARS-CoV-2 infections than the unvaccinated patients (P = .017). The hazard ratio was 0.74 (95% CI: 0.54-0.89). IV may partially reduce the risk of SARS-CoV-2 infection.

HLA status in patients with chronic spontaneous urticaria.

UNLABELLED: Chronic spontaneous urticaria (CSU) is the most common form of chronic urticaria. A considerable amount of data supports an immunological basis for CSU. Some research has focused on the association between chronic urticaria and specific human leukocyte antigen (HLA) alleles. The aim of this study was to investigate the HLA status of Polish patients diagnosed with CSU. METHODS: The standard complement-dependent microlymphocytotoxicity assay and PCR amplification with sequence-specific primers were used to analyze HLA alleles in 115 patients diagnosed with CSU, and the results were compared to those from 162 healthy, genetically unrelated individuals. RESULTS: Among the HLA-A alleles, A-33 occurred significantly more often in the control group (p < 0.01). Analysis of the HLA-B allele frequencies revealed the prevalence of the B44 antigen in the study group (p < 0.0001). Frequencies of HLA-C alleles and HLA-DQ did not differ significantly between the groups. Among the HLA class II alleles, DRB1*04 was observed significantly more often in the study population (p < 0.001), mainly in the autoimmunological subtype of urticaria. CONCLUSION: HLA alleles may be involved in CSU development or play a protective role in CSU.

Locus 1q21 Gene expression changes in atopic dermatitis skin lesions: deregulation of small proline-rich region 1A.

BACKGROUND: Discovery of the significant impact of filaggrin (FLG) mutations on the genetic predisposition to atopic dermatitis (AD) focused attention on the 1q21 locus, where not only FLG but also other epidermal genes are located. In the present study, we compared 1q21 gene expression in lesional versus nonlesional AD skin. METHODS: A real-time quantitative PCR analysis of 10 1q21 genes, selected on the basis of a previous microarray study, was performed in skin biopsies from 33 individuals with AD. Three alternative pathway keratins were also evaluated. RESULTS: In chronic AD skin lesions, we observed an increase in RNA encoding involucrin, S100 calcium-binding proteins A2 and A7-A9 and small proline-rich region (SPRR) proteins 1A and 2C, with fold changes ranging from 2.0 for S100A2 to 15.4 for S100A8 (p < 0.001, Bonferroni corrected), in parallel to the overexpression of the alternative pathway keratins 6A, 6B and 16. The loricrin (LOR) expression level was significantly decreased in lesional AD skin (fold change 0.5; p < 0.01). The expression of the majority of 1q21 genes and alternative keratins was closely correlated; however, for SPRR1A (and SPRR2C) in lesional skin, the correlation with other genes was lost. CONCLUSIONS: We hypothesize that the deregulated increase in SPRR1A expression in chronic atopic skin lesions reflects an insufficient rise in SPRR transcripts, unable to compensate for the lack of LOR and thus contributing to the persistence of chronic AD skin lesions. Turning off the stress response in the skin may be regarded as a goal in the treatment of AD skin lesions, and SPRR genes might be targets for such an approach.