Up-regulated serum levels of soluble CD25 and soluble CD163 in pediatric patients with SARS-CoV-2.

Similar to hemophagocytic lymphohistiocytosis (HLH), some patients with SARS-CoV-2 have cytokine storm. Serum soluble interleukin-2 receptor (sCD25) and soluble CD163 (sCD163) are potential diagnostic biomarkers for HLH that help in guiding its treatment. This study was the first to investigate serum sCD25 and sCD163 levels in SARS-CoV-2. Serum sCD25 and sCD163 were measured by ELISA in 29 patients with SARS-CoV-2, aged between 2 months and 16 years (13 had COVID-19 and 16 had multisystem inflammatory syndrome in children (MIS-C)), in comparison to 30 age- and sex-matched healthy control children and 10 patients with HLH. Levels of these markers were re-measured in 21 patients with SARS-CoV-2 who were followed up 3 months after recovery. Patients with SARS-CoV-2 had significantly higher serum sCD25 and sCD163 than healthy control children (P < 0.001). SARS-CoV-2 patients had significantly higher sCD25 than patients with HLH (P < 0.05). Serum sCD25 was a good differentiating marker between patients with SARS-CoV-2 and HLH. Although there was a significant decrease of serum sCD25 and sCD163 of the 21 SARS-CoV-2 patients who were followed up, these levels were still significantly higher than the healthy controls levels (P < 0.001).  Conclusion: Serum sCD25 and sCD163 levels were up-regulated in SARS-CoV-2 patients. Serum sCD25 was a good differentiating marker between SARS-CoV-2 and HLH. This initial report requires further studies, on large scales, to investigate the relationship between SARS-CoV-2 and both sCD25 and sCD163, including the disease severity and outcome. The therapeutic role of sCD25 and sCD163 antagonists should also be studied in SARS-CoV-2 patients. What is Known: • Similar to hemophagocytic lymphohistiocytosis (HLH), some patients with COVID-19 have cytokine storm due to excessive pro-inflammatory host response. • Serum soluble interleukin-2 receptor (sCD25) and soluble CD163 (sCD163) are potential diagnostic biomarkers for HLH. Monitoring of serum sCD25 and sCD163 levels can also help in guiding the treatment. What is New: • Serum sCD25 and sCD163 levels are up-regulated in patients with COVID-19, including patients presenting with multisystem inflammatory syndrome in children (MIS-C). • Serum sCD25 is a good differentiating marker between SARS-CoV-2 and HLH.

Up-regulated serum levels of TAM receptor tyrosine kinases in a group of Egyptian autistic children.

TAM receptor family belongs to receptor tyrosine kinases (TAMRTKs). It includes three receptors; Tyro-3, Axl and Mer. TAMRTKs has a great role in resolution of inflammation due to their role in clearance of apoptotic cells by macrophages. Dysregulated TAM signaling pathways are associated with many autoimmune diseases and chronic inflammatory disorders. Autism may be an autoimmune disease in some patients. This work was the first study that investigated serum levels of the soluble ectodomain shed TAMRTKs in a group of autistic children. Serum levels of TAMRTKs were measured by ELISA in 30 autistic children aged between 3.5 and 11 years and 30 age and sex-matched healthy control children. Serum levels of TAMRTKs were significantly higher in autistic children than healthy control children (P < 0.001). Patients with severe autism had significantly higher serum levels of TAMRTKs than patients with mild to moderate autism (P < 0.01). In addition, there were significant positive correlations between scores of the Childhood Autism Rating Scale (CARS) and serum levels of TAMRTKs in autistic patients, (P < 0.01). In conclusions, serum levels of TAMRTKs were up-regulated in autistic children with significant positive correlations with the degree of the disease severity. This initial report requires further studies to investigate the relationship between TAMRTKs and autism.

Plasma levels of nerve growth factor in Egyptian autistic children: Relation to hyperserotonemia and autoimmunity.

Hyperserotonemia and brain-specific autoantibodies are detected in some autistic children. Nerve growth factor (NGF) stimulates the proliferation of B lymphocytes with production of antibodies and also increases mast cell serotonin release. This work was the first to investigate the relationship between plasma NGF and both hyperserotonemia and the frequency of serum anti-myelin basic protein (anti-MBP) auto-antibodies in 22 autistic children aged between 4 and 12 years and 22 healthy-matched controls. Levels of NGF, serotonin and anti-MBP were significantly higher in autistic children than healthy control children (P < 0.001). There was a significant positive correlation between NGF and serotonin levels in autistic patients (P < 0.01). In contrast, there was a non-significant correlation between NGF and anti-MBP levels (P > 0.05). In conclusions, serum NGF levels were elevated and significantly correlated to hyperserotonemia found in many autistic children.

Impact of Auditory Integration Therapy (AIT) on the Plasma Levels of Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Autism Spectrum Disorder.

Neurotrophic factors, including the glial cell line-derived neurotrophic factor (GDNF), are of importance for synaptic plasticity regulation, intended as the synapses' ability to strengthen or weaken their responses to differences in neuronal activity. Such plasticity is essential for sensory processing, which has been shown to be impaired in autism spectrum disorder (ASD). This study is the first to investigate the impact of auditory integration therapy (AIT) of sensory processing abnormalities in autism on plasma GDNF levels. Fifteen ASD children, aged between 5 and 12 years, were enrolled and underwent the present research study. AIT was performed throughout 10 days with a 30-min session twice a day. Before and after AIT, Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma GDNF levels were assayed by an EIA test. A substantial decline in autistic behavior was observed after AIT in the scaling parameters used. Median plasma GDNF level was 52.142 pg/ml before AIT. This level greatly increased immediately after AIT to 242.05 pg/ml (P < 0.001). The levels were depressed to 154.00 pg/ml and 125.594 pg/ml 1 month and 3 months later, respectively, but they were still significantly higher compared with the levels before the treatment (P = 0.001, P = 0.01, respectively). There was an improvement in the measures of autism severity as an effect of AIT which induced the up-regulation of GDNF in plasma. Further research, on a large scale, is needed to evaluate if the cognitive improvement of ASD children after AIT is related or not connected to the up-regulation of GDNF.

The positive association between elevated blood lead levels and brain-specific autoantibodies in autistic children from low lead-polluted areas.

The underlying pathogenic mechanism in autoimmune disorders is the formation of autoantibodies. In children with autism spectrum disorder (ASD), it has been documented increased levels of brain-specific autoantibodies. Furthermore, lead (Pb) has been identified as one of the main neurotoxicants acting as environmental triggers for ASD as it induces neuroinflammation and autoimmunity. The present study is the first to explore a potential relationship between the levels of blood lead (BPb) and seropositivity of anti-ribosomal P protein antibodies in ASD children. Levels of BPb and serum anti-ribosomal P protein antibodies were measured in 60 children with ASD and 60 healthy control matched children, aged between 5 and 12 years, recruited from low Pb-polluted areas. The levels of BPb were significantly higher in ASD children than in healthy control children (P < 0.001). Patients with ASD had significantly higher frequency of increased BPb levels ≥10 µg/dL (43.3 %) than healthy control children (13.3 %; P < 0.001). There were significant and positive correlations between the levels of BPb, and the values of Childhood Autism Rating Scale (CARS) (P < 0.01) and IQ in children with ASD (P < 0.001). Patients with ASD showing increased levels of BPb had significantly higher frequency of seropositivity of anti-ribosomal P antibodies (92.3 %) than patients with normal BPb levels (32.3 %; P < 0.001). The findings of the present study suggest that increased levels of BPb in some children with ASD may trigger the production of serum anti-ribosomal P antibodies. Further research is warranted to determine if the production of brain autoantibodies is triggered by environmental Pb exposure in children with ASD. The possible therapeutic role of Pb chelators in ASD children should also be studied.

The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder.

Tachykinins (substance P, neurokinin A, and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases, including autism spectrum disorder (ASD). Mercury (Hg) is a neurotoxicant, and potentially one of the main environmental triggers for ASD as it induces neuroinflammation with a subsequent release of neuropeptides. This is the first study to explore the potentially causal relationship between levels of serum neurokinin A and blood mercury (BHg) in children with ASD. Levels of serum neurokinin A and BHg were measured in 84 children with ASD, aged between 3 and 10 years, and 84 healthy-matched children. There was a positive linear relationship between the Childhood Autism Rating Scale (CARS) and both serum neurokinin A and BHg. ASD children had significantly higher levels of serum neurokinin A than healthy controls (P < 0.001). Increased levels of serum neurokinin A and BHg were respectively found in 54.8 % and 42.9 % of the two groups. There was significant and positive linear relationship between levels of serum neurokinin A and BHg in children with moderate and severe ASD, but not in healthy control children. It was found that 78.3 % of the ASD patients with increased serum levels of neurokinin A had elevated BHg levels (P < 0.001). Neuroinflammation, with increased levels of neurokinin A, is seen in some children with ASD, and may be caused by elevated BHg levels. Further research is recommended to determine the pathogenic role of increased levels of serum neurokinin A and BHg in ASD. The therapeutic role of tachykinin receptor antagonists, a potential new class of anti-inflammatory medications, and Hg chelators, should also be studied in ASD.

The possible link between elevated serum levels of epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic children.

BACKGROUND: In autoimmune disorders, the underlying pathogenic mechanism is the formation of antigen-antibody complexes which trigger an inflammatory response by inducing the infiltration of neutrophils. Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78) is a chemokine that recruits and activates neutrophils, thus it could play a pathogenic role in inflammation and autoimmune disorders. Some autistic children have elevated levels of brain specific auto-antibodies. We are the first to evaluate serum expression of ENA-78 and its relation to antineuronal auto-antibodies in autistic children. METHODS: Serum ENA-78 and antineuronal auto-antibodies were measured by ELISA test in 62 autistic children aged between 4-11 years and 62 health-matched controls. RESULTS: Serum levels of ENA-78 were significantly higher in autistic children than healthy controls (P < 0.001). Increased serum levels of ENA-78 have been found in 69.35% of autistic patients. In addition, autistic children had significantly higher percent positivity of serum antineuronal auto-antibodies (64.5%) than healthy controls (6.45%), P < 0.001. There was a significant positive association between the positivity of serum antineuronal auto-antibodies and the elevated levels of serum ENA-78 (P < 0.001) in autistic children. CONCLUSIONS: Serum levels of ENA-78 were elevated in autistic children and they were significantly associated with the increased levels of serum antineuronal auto-antibodies. However, these data should be treated with caution until further research is conducted to determine the pathogenic role of ENA-78 in autism and its relation to brain specific auto-antibodies that have been found in some autistic children. The possible therapeutic role of ENA-78 antagonist in autistic children should be also studied.

Serum antinucleosome-specific antibody as a marker of autoimmunity in children with autism.

BACKGROUND: Increasing evidence of autoimmune phenomena in some individuals with autism could represent the presence of altered or inappropriate immune responses in this disorder. The role of the nucleosome in the induction of antibody response in some autoimmune-mediated tissue damage may provide novel targets for treatment. Due to the paucity of studies investigating the frequency of systemic auto-antibodies in autism, we are the first to investigate the frequency of antinucleosome-specific antibodies in a group of autistic children. METHODS: Serum antinucleosome-specific antibodies were measured by ELISA in 60 autistic children, between the ages of 3 and 12 years, in comparison to 60 healthy children. Autistic severity was assessed using the Childhood Autism Rating Scale (CARS). RESULTS: Autistic children had significantly higher serum antinucleosome-specific antibodies than healthy children (P <0.001). The seropositivity of antinucleosome-specific antibodies was found in 46.7% of autistic children. Autistic children with a family history of autoimmunity (40%) had a significantly higher frequency of serum antinucleosome-specific antibodies (83.3%) than patients without such a history (22.2%, P <0.001). CONCLUSIONS: Serum levels of antinucleosome-specific antibodies were increased in some autistic children. However, these data should be treated with caution until further investigations are performed with a larger subject population to determine whether these antibodies have a role in the induction of autoimmunity in a subgroup of autistic children. The role of immunotherapy in children with autism should be also studied.

The possible relationship between allergic manifestations and elevated serum levels of brain specific auto-antibodies in autistic children.

Etiology of autism has become an area of a significant controversy. Allergy induced autism is an area of research wherein immune responses to some allergens may play a pathogenic role in autism. Allergy may induce the production of brain specific auto-antibodies in a subgroup of autistic children. We are the first to investigate the possible link between allergic manifestations and serum levels of both anti-myelin basic protein (anti-MBP) and anti-myelin associated glycoprotein (anti-MAG) brain-specific auto-antibodies, which were measured by ELISA method, in 42 autistic children in comparison to 42 healthy-matched children. Allergic manifestations (bronchial asthma, atopic dermatitis and/or allergic rhinitis) were found in 47.6% of autistic patients. Increased serum levels of anti-MBP and anti-MAG auto-antibodies were found in 57.1% and 66.7%, respectively of autistic children. In addition, 78.5% of autistic children had increased serum levels of both anti-MBP and/or anti-MAG auto-antibodies. Autistic patients with allergic manifestations had significantly higher serum levels of anti-MBP and anti-MAG auto-antibodies than those without these manifestations (P<0.001 and P=0.001, respectively). In conclusion, allergy may be a contributing factor to the increased serum levels of anti-MBP and anti-MAG auto-antibodies in some autistic children. Indeed, we need to know more about the links between allergy, immune system and brain in autism for finding new therapeutic modalities in autism.

Elevated serum levels of macrophage-derived chemokine and thymus and activation-regulated chemokine in autistic children.

BACKGROUND: In some autistic children, there is an imbalance of T helper (Th)1/Th2 lymphocytes toward Th2, which may be responsible for the induction of the production of autoantibodies in these children. Th2 lymphocytes express CCR4 receptors. CCR4 ligands include macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC). They direct trafficking and recruitment of Th2 cells. We are the first to measure serum levels of CCR4 ligands in relation to the degree of the severity of autism. METHODS: Serum concentrations of MDC and TARC were measured, by quantitative sandwich enzyme immunoassay technique, in 56 autistic children and 32 healthy matched children. RESULTS: Autistic children had significantly higher serum levels of MDC and TARC than healthy controls (P <0.001 and P <0.001, respectively). Children with severe autism had significantly higher serum levels of MDC and TARC than patients with mild to moderate autism (P <0.001 and P = 0.01, respectively). In addition, there were significant positive correlations between CARS and serum levels of both MDC (P <0.001) and TARC (P <0.001) in children with autism. There were significant positive correlations between serum levels of MDC and TARC in autistic children (P <0.001). CONCLUSIONS: Serum levels of CCR4 ligands were elevated in autistic children and they were significantly correlated to the degree of the severity of autism. However, further research is warranted to determine the pathogenic role of CCR4 ligands in autism and to shed light on the therapeutic role of CCR4-ligand antagonism in autistic children.

Elevated serum levels of interleukin-17A in children with autism.

BACKGROUND: The T-helper (Th)1/Th2 dichotomy dominated the field of immune regulation until interleukin (IL)-17-expressing T cells (Th17) were proposed to be a third lineage of helper T cells, the key players in the pathogenesis of autoimmune disorders. Autoimmunity to brain tissue may play a pathogenic role in autism. IL-17A is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. The aim of this study was to measure serum levels of IL-17A in relation to the degree of the severity of autism. METHODS: Serum IL-17A levels were measured by ELISA in 45 children with autism and 40 matched healthy controls. RESULTS: Children with autism had significantly higher serum IL-17A levels than healthy controls (P <0.001), with increased serum levels of IL-17A found in 48.9% of the autism group. Patients with severe autism had significantly higher serum IL-17A levels than those with mild to moderate autism (P=0.01), and raised serum IL-17A levels were significantly more common in children with severe autism (67.9%) than in those with mild to moderate autism (17.6%), P=0.001. CONCLUSIONS: Serum IL-17A levels were raised in the group with autism, and the levels correlated significantly with the severity of autism. This is the first study to measure levels of IL-17A in relation to the severity of autism, to our knowledge. Further research, with a larger subject population, is warranted to determine whether the increase of serum IL-17A levels plasma has a pathogenic role in autism, and whether anti- IL-17A therapy could be useful.

A lack of association between elevated serum levels of S100B protein and autoimmunity in autistic children.

BACKGROUND: S100B is a calcium-binding protein that is produced primarily by astrocytes. Increased serum S100B protein levels reflect neurological damage. Autoimmunity may have a role in the pathogenesis of autism in some patients. Autoantibodies may cross the blood-brain barrier and combine with brain tissue antigens, forming immune complexes and resulting in neurological damage. We are the first to investigate the relationship between serum levels of S100B protein, a marker of neuronal damage, and antiribosomal P protein antibodies in autistic children. METHODS: Serum S100B protein and antiribosomal P antibodies were measured in 64 autistic children in comparison to 46 matched healthy children. RESULTS: Autistic children had significantly higher serum S100B protein levels than healthy controls (P < 0.001). Children with severe autism had significantly higher serum S100B protein than patients with mild to moderate autism (P = 0.01). Increased serum levels of antiribosomal P antibodies were found in 40.6% of autistic children. There were no significant correlations between serum levels of S100B protein and antiribosomal P antibodies (P = 0.29). CONCLUSIONS: S100B protein levels were elevated in autistic children and significantly correlated to autistic severity. This may indicate the presence of an underlying neuropathological condition in autistic patients. Antiribosomal P antibodies may not be a possible contributing factor to the elevated serum levels of S100B protein in some autistic children. However, further research is warranted to investigate the possible link between serum S100B protein levels and other autoantibodies, which are possible indicators of autoimmunity to central nervous system in autism.

The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children.

BACKGROUND: Autism may involve an autoimmune pathogenesis. Immunotherapy may have a role in autistic children who have brain auto-antibodies. AIM: This study aimed to investigate the frequency of serum antineuronal auto-antibodies, as indicators of the presence of autoimmunity to brain, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism. METHODS: Serum antineuronal antibodies were measured, by indirect immunofluorescence technique, in 80 autistic children, aged between 6 and 12 years, in comparison to 80 healthy-matched children. The severity of autism was assessed by using the Childhood Autism Rating Scale. RESULTS: Autistic children had significantly higher percent positivity of serum antineuronal antibodies (62.5%) than healthy controls (5%), P<0.001. The frequency of the positivity of serum antineuronal antibodies was significantly higher in children with severe autism (87.5%) than children with mild to moderate autism (25%), P<0.001. Similarly, the frequency of the positivity of these antibodies was significantly higher in female children with autism (90%) than male autistic children (53.3%), P=0.001. CONCLUSIONS: Serum antineuronal antibodies were found in a subgroup of autistic children and they were significantly correlated to the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the etiopathogenic role of antineuronal antibodies in autism. The role of immunotherapy in autistic patients, who are seropositive for antineuronal antibodies, should also be studied.

A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children.

BACKGROUND: One of the most consistent biological findings in autism is the elevated blood serotonin levels. Immune abnormalities, including autoimmunity with production of brain specific auto-antibodies, are also commonly observed in this disorder. Hyperserotonemia may be one of the contributing factors to autoimmunity in some patients with autism through the reduction of T-helper (Th) 1-type cytokines. We are the first to investigate the possible role of hyperserotonemia in the induction of autoimmunity, as indicated by serum anti-myelin-basic protein (anti-MBP) auto-antibodies, in autism. METHODS: Serum levels of serotonin and anti-MBP auto-antibodies were measured, by ELISA, in 50 autistic patients, aged between 5 and 12 years, and 30 healthy-matched children. RESULTS: Autistic children had significantly higher serum levels of serotonin and anti-MBP auto-antibodies than healthy children (P < 0.001 and P < 0.001, respectively). Increased serum levels of serotonin and anti-MBP auto-antibodies were found in 92% and 80%, respectively of autistic patients. Patients with severe autism had significantly higher serum serotonin levels than children with mild to moderate autism (P < 0.001). Serum serotonin levels had no significant correlations with serum levels of anti-MBP auto-antibodies in autistic patients (P = 0.39). CONCLUSIONS: Hyperserotonemia may not be one of the contributing factors to the increased frequency of serum anti-MBP auto-antibodies in some autistic children. These data should be treated with caution until further investigations are performed. However, inclusion of serum serotonin levels as a correlate may be useful in other future immune studies in autism to help unravel the long-standing mystery of hyperserotonemia and its possible role in the pathophysiology of this disorder.

Lead exposure and its association with pubertal development in school-age Egyptian children: pilot study.

BACKGROUND: The aim of the present study was to determine blood lead levels in a group of Egyptian school-age children and assess its relationship to pubertal development. METHODS: Forty-one children were recruited from high- and low-pollution areas in Cairo, Egypt. Sexual maturation was evaluated using Tanner score. Measurements of blood lead and serum levels of follicle stimulation hormone (FSH), luteinizing hormone (LH), estradiol in girls and testosterone in boys were performed for included subjects. RESULTS: A total of 51.2% of children had high blood lead levels (>or=10 microg/dL). Boys with high lead levels had delayed pubertal maturation compared to those with low lead levels. Breast staging of sexual maturation was significantly delayed in girls with high lead levels. FSH and LH were significantly reduced in children of both sexes, and testosterone levels were reduced in boys with high lead. CONCLUSION: These findings consolidate the cumulative medical evidence of the deleterious effect of high lead levels on pubertal development, possibly through the hypothalamic-pituitary-gonadal axis.

Serum anti-myelin-associated glycoprotein antibodies in Egyptian autistic children.

Autoimmunity to brain could play an etiopathogenic role in a subgroup of autistic patients. The frequency of serum anti-myelin-associated glycoprotein antibodies, as an index for autoimmunity to brain, and their relation to family history of autoimmunity were investigated in 32 autistic and 32 healthy matched children. Autistic children had significantly higher serum anti-myelin-associated glycoprotein antibodies than healthy children (2100 [1995] and 1138 [87.5] Buhlmann titre unit, P < .001). Anti-myelin-associated glycoprotein positivity was elicited in 62.5% of autistic children. Family history of autoimmunity in autistic children (50%) was significantly higher than controls (9.4%). Anti-myelin-associated glycoprotein serum levels were significantly higher in autistic children with than those without such history (P < .05). In conclusion, autism could be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further studies are warranted to shed light on the etiopathogenic role of anti-myelin-associated glycoprotein antibodies and the role of immunotherapy in autism.

Serum concentrations of CCR4 ligands in relation to clinical severity of atopic dermatitis in Egyptian children.

T helper 2 (Th2) lymphocytes, the key effector cells in pathogenesis of atopic dermatitis (AD), express CCR4 receptors. CCR4 ligands (macrophage-derived chemokine 'MDC' and thymus and activation-regulated chemokine 'TARC') direct trafficking and recruitment of Th2 cells into lesional skin in AD. These chemokines appear to be useful inflammatory markers for assessing severity of AD in adults. However, the same results have not been replicated in children. Therefore, we were stimulated to elucidate the expression of CCR4 ligands in children with AD and their relation to clinical disease severity. To investigate this, serum concentrations of CCR4 ligands were determined in 60 children, of whom 30 had AD and 30 were healthy matched subjects. Patients were classified into mild (n = 8), moderate (n = 12) and severe (n = 10) according to the objective scoring AD (obj-SCORAD) index. Serum concentrations of MDC and TARC were significantly increased in children with AD (2697 +/- 982.6 pg/ml and 945.5 +/- 494.7 pg/ml, respectively) compared with controls (357.2 +/- 233.2 pg/ml and 214.2 +/- 116.6 pg/ml, respectively, p < 0.0001). Serum levels of both chemokines went hand in hand with disease severity as they were significantly higher in severe than moderate and in moderate than mild AD. In addition, they correlated positively with obj-SCORAD (r = 0.99 for both, p < 0.0001). Furthermore, both chemokines had significant positive correlations to blood eosinophil counts and serum immunoglobulin E. In conclusion, serum CCR4 ligands may be useful inflammatory markers for assessing AD severity in children. Further studies may pave way for CCR4 ligands antagonism among the adjuvant therapeutic strategies of AD.