SARS-CoV-2 Infection as a Possible Trigger for IgA-Associated Vasculitis: A Case Report.

BACKGROUND: IgA-associated vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP) disease, is the most common type of systemic vasculitis observed during developmental age. Available published studies associate the outbreak of the disease with streptococci, adenovirus, parvovirus, mycoplasma, respiratory syncytial virus (RSV), and influenza infection in approximately 50% of patients with HSP, while some emerging reports have described a few cases of COVID-19 infection being associated with HSP in both adults and children. CASE PRESENTATION: a 7-year-old girl was diagnosed with HSP, fulfilling the four required clinical criteria (palpable purpura and abdominal pain, arthralgia and edema, and periodic renal involvement). Infection with SARS-CoV-2 was confirmed via the presence of IgM and IgG antibodies. The disclosure of the Henoch-Schönlein purpura (HSP) disease was preceded by a mild, symptomatically treated infection of the upper respiratory tract. High levels of inflammatory markers were observed during hospitalization, including leukocytosis, an increased neutrophil count and a high neutrophil-to-lymphocyte ratio (NLR). All of these markers are associated with IgAV gastrointestinal bleeding, which was also associated with rotavirus diarrhea observed in the patient. CONCLUSIONS: This case presented by us and similar cases presented by other authors indicate the possible role of SARS-CoV-2 in the development of HSP, but this assumption requires further research and evidence-based verification.

Assessment of selected interleukins (IL-6, IL-17A, IL-18, IL-23) and chemokines (RANTES, IP-10) in children with acute and chronic urticaria.

BACKGROUND: Urticarial lesions develop as a result of the activation of mast cells which, through the release of mediators, influence the formation of local inflammatory infiltrates. Changes in the expression of many cytokines and chemokines are observed in the course of urticaria. The aim of the study was to evaluate serum levels of interleukin (IL)-6, IL-17A, IL-18, IL-23, regulated on activation, normal T cell expressed and secreted (RANTES) and interferon (IFN)-γ-inducible protein-10 (IP-10) in children with acute urticaria and exacerbation of chronic urticaria in comparison to healthy volunteers. Moreover, we made an attempt to identify factors associated with the acute phase of urticaria and factors predicting the course of the disease among the studied parameters. METHODS: We retrospectively analyzed 32 children with acute urticaria and 32 children with chronic urticaria. The control group consisted of 40 healthy children. Each patient was clinically evaluated. Serum concentrations of selected cytokines and chemokines were determined by using enzyme-linked immunosorbent assay. RESULTS: Patients with acute and chronic urticaria had higher concentrations of IL-6 and IL-17A (p < 0.001) and lower concentrations of IL-18, IL-23, RANTES and IP-10 (p < 0.001) as compared to the control group. A significant association between IL-6 and IP-10 with the acute phase of urticaria has been demonstrated. There was no correlation of the studied cytokines and chemokines with disease activity. CONCLUSIONS: In children with acute phase of urticaria, the cytokine serum concentration differs compared to healthy subjects. IL-6 and IP-10 seem to be useful in differentiating children with acute phase of urticaria and healthy ones. The search for factors predicting the course of the disease requires further studies.

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. MATERIAL AND METHODS: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. CONCLUSIONS: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

Analysis of the association between kidney injury biomarkers concentration and nephritis in immunoglobulin A vasculitis: A pediatric cohort study.

OBJECTIVE: The aim of this study was to investigate the clinical course, selected biochemical parameters and concentrations of renal injury biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and liver-fatty acid binding protein (L-FABP) in patients with immunoglobulin A vasculitis (IgAV) to identify the markers associated with nephritis in the course of the disease (IgAVN). METHODS: The study involved 29 children with IgAV and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). Initial laboratory tests, determining the concentrations of NGAL, KIM-1 and L-FABP in serum and urine, were conducted on children from the study group in an acute phase of IgAV as well as after an average of 6 months, during a follow-up visit. The interconnection between renal involvement, anthropometric measurements, epidemiological data, laboratory parameters and levels of examined biomarkers have been thoroughly evaluated. RESULTS: The serum and urine levels of NGAL, KIM-1 and L-FABP were significantly higher in children with an acute phase of IgAV as compared to the control group (P < .001) and markedly lower during follow-up retesting in comparison with the values obtained at inclusion (P < .001). However, the concentration of none of the evaluated biomarkers correlated with nephrological indices. Among all examined parameters, only male subjects were associated with nephritis (P = .017). CONCLUSIONS: We have established no evident association between the concentrations of NGAL, KIM-1 and L-FABP and nephritis in the course of IgAV in children. Additionally, we confirmed a significant male predominance in patients with nephritis.

The role of adipokines in the pathogenesis and course of selected respiratory diseases.

Adipose tissue is also a secretory organ producing active substances called adipokines. Some of them (apelin, resistin, adiponectin, leptin, chemerin, or visfatin) may play a role in the pathogenesis and course of respiratory diseases, e.g. COPD, asthma, pulmonary hypertension, or lung cancer. There are limited and conflicting data on the role of adipokines in asthma. It has been confirmed, however, that visfatin and leptin can be markers of inflammation in COPD. Elevated concentrations of leptin and resistin play a pro-inflammatory role in the development of cancer cachexia. The role of adipokines has also been demonstrated in pulmonary hypertension, and the apelinadiponectin axis disruption may exacerbate pulmonary hypertension.

Evaluation of adipokines in children with cystic fibrosis.

INTRODUCTION: Patients with CF present numerous pathological conditions such as malnutrition, depletion of fat-free mass, metabolic disturbances (abnormal glucose metabolism, increased insulin resistance, chronic energy deficit, local and chronic inflammation), which could affect or be associated with altered adipokines concentration Material and Methods: We aimed in this study to investigate the levels of selected adipokines such as resistin, apelin, adiponectin to demonstrate their application as possible markers of inflammation. RESULTS: Serum level of resistin was higher (p < 0.001) and adiponectin - lower (p=0.02) in CF children than in healthy children. There was no difference in serum apelin level between two examined groups. However, values of adiponectin/BMI and apelin/BMI ratios in CF did not differ significantly from controls. Higher values of resistin/BMI ratio in CF in comparison to controls were observed Serum resistin/adiponectin ratio was significantly higher in CF patients than in controls (p < 0.0001). Resistin/BMI ratio correlated negatively with FEV1 (R:-48,p < 0.043). Serum resistin/adiponectin ratio correlated negatively with FEV1/FVC (R:-49, p=0.04), Adipokines showed no correlation with BMI and BMI-SDS, glucose, total cholesterol, and LDL-, HDL-cholesterol, triglyceride serum levels. Spirometric parameters FEV1, FVC, VC correlated negatively with serum glucose levels (R: -0.55, p < 0.018; R: -0.65 p < 0.0025; R:-0.76, p < 0.0008 respectively). FEV1 and FVC correlated positively with BMI-SDS (R:0.58, p < 0.01; R:0.5, p < 0.036, respectively). CONCLUSIONS: A significant increase in resistin concentration expressed also as resistin/BMI, and resistin/adiponectin ratios, observed in children with CF may suggests that this adipokine is involved in the inflammatory process underlying the disease and is related to worse spirometric parameters describing airways obstruction.

Atopic allergy and chronic inflammation of the oral mucosa in a 3-year-old boy after heart transplantation - diagnostic and therapeutic difficulties.

In recent years, we have been observing an increased proportion of atopic diseases in children after solid organ transplantation. The pathogenesis of post-transplantation allergy is not completely understood and probably involves several factors, including immunosuppressive therapy. In this paper we present a case of 3-year old boy, after orthotopic heart transplantation at 6 months of age, with symptoms of food allergy associated with atopic dermatitis and changes in the orofacial area. The mentioned symptoms and elevated levels of total and specific IgE occurred with a year of transplant. Because of failure to achieve remission after typical allergy therapy we suspected that the reason of allergy in this case can be immunosuppressive therapy.

The etiology and clinical manifestation of erythema nodosum in hospitalized children - analysis of 12 cases. Preliminary report.

AIM: To analyse etiologic factors and the clinical course of erythema nodosum in hospitalized children. MATERIAL AND METHODS: A retrospective study of 12 children and young people (7 girls and 5 boys) admitted to the Paediatric Clinic in Zabrze with erythema nodosum was performed from January 2004 to February 2014. The patients' mean age on admission was 11.9 years (2-16). RESULTS: In ten of the 12 patients elevated CRP was identified - from 10 mg/L to 131.5 mg/L, which is proof of an ongoing inflammatory process. Only two patients had a CRP level below 5 mg/L. Three of the 12 patients were diagnosed with Crohn's Disease, one with diarrhoea (Salmonella was cultured and antigen Rotavirus was found), one with arthritis, one with bilateral cervical lymphadenopathy, three with Streptococcal infection, two had elevated anti-streptolysin O level (ASO). CONCLUSION: The present research may confirm the hypothesis that EN could be the first sign of systemic diseases. However, it requires further studies because of the limited number of patients.

[Etiology and clinical course of urticaria in hospitalized children]. / Etiologia i przebieg kliniczny pokrzywkiu hospitalizowanych dzieci.

INTRODUCTION: Data concerning the epidemiology, etiology and clinical course of childhood urticaria are still under discussion. AIM: To investigate the clinical presentation of urticaria in hospitalized children and to define its possible etiologies. MATERIAL AND METHODS: Ninety eight children (male/female 42/57) aged 0.2-17.6 years, (mean age 8.22±0.55) hospitalized due to urticaria were included in the study. The nature and localization of skin lesions, accompanying diseases and diagnostic test results were analyzed. RESULTS: Sixty nine children (70.4%) were diagnosed as having acute, 22 (22.5%) acute recurrent and 7 (7.1%) chronic urticaria. Allergic diseases, family history of atopy and adenoid hypertrophy and/or chronic tonsillitis were present respectively in 10 (10.2%), 28 (28.6%), 21 (21.4%) children. In 32 children (46.3%) with acute urticaria, in 8 (36.3%) with recurrent and in 2 (28.5%) with chronic urticaria skin lesions covered the whole body. Serum C-reactive protein and leukocyte levels in children with acute urticaria were significantly higher compared to children with chronic urticaria (p<0.05). The serum IgE levels, the percentage and absolute count of eosinophils were similar in different forms of urticaria. Probable etiology in 62/69 children with acute urticaria (respiratory tract infections - 43, drugs - 8, lambliosis - 6, food allergy - 2, antiallergy shots - 2, urinary tract infection - 1 child), in 9/22 children with recurrent urticaria (respiratory tract infection - 7, lambliosis - 2 children) and in 3/7 children with chronic urticaria (physical urticaria - 2, urinary tract infection - 1 child) was determined. CONCLUSIONS: Among children with urticaria, the most frequent cause for hospitalization is acute urticaria. The outbreak of hives wheels is usually triggered by upper respiratory tract infection. IgE-related allergy is a rare reason of childhood urticaria. In more than 50% of cases of recurrent and chronic urticaria the etiology was not determined.

Serum resistin levels are elevated in schoolchildren with atopic asthma.

OBJECTIVES: There are limited data on the role of adipokines in atopic asthma. DESIGN AND SETTING: To determine serum levels of resistin in asthmatic children in relation to body weight, asthma severity and gender, serum resistin (RES) levels were measured using ELISA in 89 asthmatic children (61 boys and 28 girls, aged 7.0-17.0 years) and in 33 healthy children. Among examined asthmatics 59 (19 girls and 40 boys) had normal weight (ANW) and 30 (9 girls and 21 boys) were obese (AO). RESULTS: The mean serum levels of resistin were significantly (p<0.01) higher in all non-obese asthmatic children (4.11±0.1 ng/mL) than in healthy children (3.83±0.1 ng/mL). After stratifying by gender only ANW boys and AO boys had significantly higher RES levels than boys from control group. Both AO (4.4±0.2 ng/mL) and ANW girls (4.38±0.2 ng/mL) as well as girls from control (4.09±0.1) group showed significantly higher mean RES serum concentrations than boys from corresponding groups (3.99±0.1 ng/ml, 3.83±0.17 ng/ml and 3.44±0.06 ng/ml, respectively). No relationship between examined adipokine levels and asthma severity, spirometric parameters, degree of allergic sensitization, BMI, BMI-SDS was stated. CONCLUSION: Increased serum RES in children with atopic asthma suggest that this adipokine may be implicated in its pathogenesis.

Evaluation of adipokines: apelin, visfatin, and resistin in children with atopic dermatitis.

Very little is known about the role of adipokines in atopic dermatitis (AD) in children. This study aimed at analyzing the serum levels of resistin, apelin, and visfatin in children with AD in relation to body weight, AD severity, and gender. Serum concentration of adipokines was measured in 27 children with AD and in 46 healthy subjects. Selected biochemical parameters were evaluated and skin prick test was performed. Serum levels of resistin and apelin were significantly higher, whereas serum visfatin concentration was significantly lower in children with AD versus healthy controls, although an increase in resistin levels was exclusively demonstrated in boys. In AD group, a significant increase in apelin levels in girls was documented. There was no relationship between adipokines levels and the degree of allergic sensitization. Receiver operating characteristic curve analysis demonstrated that the serum apelin cutoff value differentiating children with AD from those without was >137.8 pg/mL. Resistin and visfatin cutoff values were >3.8 ng/mL and ≤ 2.13 ng/mL, respectively. Apelin and visfatin can serve as excellent indicators to distinguish children with AD from those without disease.

Cytokine production by peripheral blood CD4+ and CD8+ T cells in atopic childhood asthma.

There are conflicting studies on T cell cytokine production in childhood asthma. In this study intracellular cytokine expression of IL-2, IL-4, IL-10, IL-13, IFN-γ, and TNF-α in CD4(+) and CD8(+) T cells in children with atopic asthma were measured by flow cytometry. Results. A significant increase in the percentage of CD4(+) and CD8(+) T cells producing IL-4 and IL-13 and decrease in the percentage of CD4(+) producing IFN-γ in asthmatic children was found. The percentage of CD4(+)/IL-13(+) was significantly higher in severe asthma than in children with intermittent disease symptoms. Severity of asthma was associated with increased both serum IgE and frequencies of CD4(+)/IL-13(+) T cells, as well as duration of disease. Moreover, a decrease in FEV(1), FEV(1)/FVC was observed in relation to the severity of asthma. Changes in cytokine profile in CD8(+) subpopulation didn't depend on the severity of the disease. Conclusions. Increased production of IL-4 and IL-13 in both CD4(+) and CD8(+) T cells accompanied by decreased IFN-γ expression in CD4(+) T cells may be evidence that both lymphocyte subpopulations are implicated in the pathogenesis of asthma. Relationship of CD4(+)/IL-13(+) T cells with disease activity suggests that this lymphocyte subset may have a prominent role in childhood asthma.

Intracellular production of IL-2, IL-4, IFN-gamma, and TNF-alpha by peripheral blood CD3+ and CD4+ T cells in children with atopic dermatitis.

The role of the type-2 T helper (Th2) cell-mediated immune response in the immunopathogenesis of atopic dermatitis (AD) is well documented. Whether polarized immunoresponse is confined to antigen-specific T cells or is distributed among all T cell subsets is still controversial. We investigated frequencies of interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) producing CD3(+) and CD4(+) T cells in peripheral blood from children with atopic dermatitis and healthy subjects with and without in vitro stimulation. Children with severe AD had a significantly lower percentage of CD4(+) T cells spontaneously expressing IL-4 compared with healthy controls (p <0.01). Polyclonal stimulation significantly increased cytokine production in both AD patients and healthy individuals. Frequencies of CD3(+) and CD4(+) producing IL-2, IL-4, IFN-gamma, and TNF-alpha after in vitro stimulation with phorbol-12-myristate 13-acetate (PMA) + ionomycin were comparable in the AD and control groups. In response to PMA/ionomycin, children with AD and asthma symptoms had a significantly lower percentage of CD3(+) T cells producing TNF-alpha. We failed to demonstrate evidence of an imbalance with respect to type-2 cytokine productions in children with AD. Comparable induction of Th1 and Th2 cytokines in polyclonally stimulated peripheral CD3(+) and CD4(+)T cells from AD patients and controls puts into question the polarized Th2 immune response as a general characteristic of T cells in children with atopic dermatitis.