Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome Associated With a Novel Mutation of FOXP3 Gene

The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, x-linked, recessive disorder characterized by dysfunction of the T regulatory (Treg) lymphocytes leading to autoimmune diseases. Herein we report a male patient with IPEX syndrome who presented with severe diarrhea, eczema, and malabsorption leading to failure to thrive and necessitating total parenteral nutrition, as well as with liver dysfunction. Laboratory investigation showed elevated liver enzymes that declined following treatment with glucocorticosteroids and immunosuppressive drugs, marked eosinophilia, increased total IgE, and decreased Treg cells. DNA analysis revealed that the patient himself was hemizygous and his mother heterozygous for the exon 10, c.1015C>T (p.Pro339Ser) mutation of the FOXP3 gene, which has not been previously reported. The current case indicates that mutations resulting in substitution of a certain amino-acid (i.e., proline 339) by different amino-acids are manifested with different IPEX phenotypes

Humoral Immunity against Measles in Mother–Infant Pairs during the First Year of Life in Greece: A Cross-Sectional Study

Measles outbreaks have surfaced in Europe during the last decades. Infants <12 months of age were the most severely affected pediatric population. The aim of this study was to investigate the duration of maternally derived measles antibodies in infants aged 1 to 12 months in relation to maternal humoral immune status and other parameters. In a prospective, cross-sectional cohort study, 124 mother/infant pairs and 63 additional infants were recruited from October 2015 through December 2019. Infants were hospitalized in a university pediatric department of a general hospital. Demographic and epidemiological data were recorded and blood samples were collected from mothers and their infants. Commercially available enzyme-linked immunosorbent assay (ELISA) was used for measuring measles antibodies. Fifty nine percent of mothers had vaccine-induced and 15% infection-acquired measles immunity. Eighty-eight percent and 94% of infants were unprotected by 5 and 10 months of age, respectively. Maternal antibody levels and infant age were significant independent predictors of infants’ antibody levels whereas the method of maternal immunity acquisition, age, and origin [Greek/non-Greek] were not. Our findings suggest that about 90% of infants are susceptible to measles beyond the age of 4 months. To our knowledge, these are the first data from Greece reported under the current community composition and epidemiological conditions

Humoral Immunity against Measles in Mother–Infant Pairs during the First Year of Life in Greece: A Cross-Sectional Study

Measles outbreaks have surfaced in Europe during the last decades. Infants <12 months of age were the most severely affected pediatric population. The aim of this study was to investigate the duration of maternally derived measles antibodies in infants aged 1 to 12 months in relation to maternal humoral immune status and other parameters. In a prospective, cross-sectional cohort study, 124 mother/infant pairs and 63 additional infants were recruited from October 2015 through December 2019. Infants were hospitalized in a university pediatric department of a general hospital. Demographic and epidemiological data were recorded and blood samples were collected from mothers and their infants. Commercially available enzyme-linked immunosorbent assay (ELISA) was used for measuring measles antibodies. Fifty nine percent of mothers had vaccine-induced and 15% infection-acquired measles immunity. Eighty-eight percent and 94% of infants were unprotected by 5 and 10 months of age, respectively. Maternal antibody levels and infant age were significant independent predictors of infants’ antibody levels whereas the method of maternal immunity acquisition, age, and origin [Greek/non-Greek] were not. Our findings suggest that about 90% of infants are susceptible to measles beyond the age of 4 months. To our knowledge, these are the first data from Greece reported under the current community composition and epidemiological conditions

SIAE Rare Variants in Juvenile Idiopathic Arthritis and Primary Antibody Deficiencies

Sialic acid acetylesterase (SIAE) deficiency was suggested to lower the levels of ligands for sialic acid-binding immunoglobulin-like receptors, decreasing the threshold for B-cell activation. In humans, studies of rare heterozygous loss-of-function mutations in SIAE gene in common autoimmune diseases, including juvenile idiopathic arthritis (JIA), yielded inconsistent results. Considering the distinct pathogenesis of the two main subtypes of JIA, autoinflammatory systemic (sJIA) and autoimmune oligo/polyarticular (aJIA), and a predisposition to autoimmunity displayed by patients and families with primary antibody deficiencies (PADs), the aim of our study was to analyze whether SIAE rare variants are associated with both the phenotype of JIA and the autoimmunity risk in families with PADs. A cohort of 69 patients with JIA, 117 healthy children, 54 patients, and family members with PADs were enrolled in the study. Three novel SIAE variants (p.Q343P, p.Y495X, and c.1320+33T>C) were found only in patients with aJIA but interestingly also in their healthy relatives without autoimmunity, while none of PAD patients or their relatives carried SIAE defects. Our results show that SIAE rare variants are not causative of autoimmunity as single defects

SIAE

Sialic acid acetylesterase (SIAE) deficiency was suggested to lower the levels of ligands for sialic acid-binding immunoglobulin-like receptors, decreasing the threshold for B-cell activation. In humans, studies of rare heterozygous loss-of-function mutations in SIAE gene in common autoimmune diseases, including juvenile idiopathic arthritis (JIA), yielded inconsistent results. Considering the distinct pathogenesis of the two main subtypes of JIA, autoinflammatory systemic (sJIA) and autoimmune oligo/polyarticular (aJIA), and a predisposition to autoimmunity displayed by patients and families with primary antibody deficiencies (PADs), the aim of our study was to analyze whether SIAE rare variants are associated with both the phenotype of JIA and the autoimmunity risk in families with PADs. A cohort of 69 patients with JIA, 117 healthy children, 54 patients, and family members with PADs were enrolled in the study. Three novel SIAE variants (p.Q343P, p.Y495X, and c.1320+33T>C) were found only in patients with aJIA but interestingly also in their healthy relatives without autoimmunity, while none of PAD patients or their relatives carried SIAE defects. Our results show that SIAE rare variants are not causative of autoimmunity as single defects

The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis

Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Thirty-one children (mean age:12.9 +/- 4.6 years) treated with anti-TNFs plus Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 32 age-matched children treated only with DMARDs were vaccinated with two doses of PCV7. After the first vaccine dose geometric mean titers (GMTs) were significantly increased for all vaccine serotypes (p &lt; 0.0001) in both groups and were found to be protective (&gt;0.35 mu g/ml) in 87-100% of all children, depending on the serotype. Children receiving anti-TNFs achieved a significantly lower GMTs against serotypes 4, 14 and 23F (p &lt; 0.05). A &gt;= 4-fold increase of the baseline titers to &gt;= 5 vaccine serotypes was observed in 50% and 75% of the anti-TNF and control patients, respectively (p = 0.0697). No patient developed vaccine-associated serious adverse events or disease flares. (C) 2010 Elsevier Ltd. All rights reserved

Candida tropicalis in a Neonatal Intensive Care Unit: Epidemiologic and Molecular Analysis of an Outbreak of Infection with an Uncommon Neonatal Pathogen

From June to July 1998, two episodes of Candida tropicalis fungemia occurred in the Aristotle University neonatal intensive care unit (ICU). To investigate this uncommon event, a prospective study of fungal colonization and infection was conducted. From December 1998 to December 1999, surveillance cultures of the oral cavities and perinea of the 593 of the 781 neonates admitted to the neonatal ICU who were expected to stay for >7 days were performed. Potential environmental reservoirs and possible risk factors for acquisition of C. tropicalis were searched for. Molecular epidemiologic studies by two methods of restriction fragment length polymorphism analysis and two methods of random amplified polymorphic DNA analysis were performed. Seventy-two neonates were colonized by yeasts (12.1%), of which 30 were colonized by Candida albicans, 17 were colonized by C. tropicalis, and 5 were colonized by Candida parapsilosis. From December 1998 to December 1999, 10 cases of fungemia occurred; 6 were due to C. parapsilosis, 2 were due to C. tropicalis, 1 was due to Candida glabrata, and 1 was due to Trichosporon asahii (12.8/1,000 admissions). Fungemia occurred more frequently in colonized than in noncolonized neonates (P < 0.0001). Genetic analysis of 11 colonization isolates and the two late blood isolates of C. tropicalis demonstrated two genotypes. One blood isolate and nine colonization isolates belonged to a single type. The fungemia/colonization ratio of C. parapsilosis (3/5) was greater than that of C. tropicalis (2/17, P = 0.05), other non-C. albicans Candida spp. (1/11, P = 0.02), or C. albicans (0/27, P = 0.05). Extensive environmental cultures revealed no common source of C. tropicalis or C. parapsilosis. There was neither prophylactic use of azoles nor other risk factors found for acquisition of C. tropicalis except for total parenteral nutrition. A substantial risk of colonization by non-C. albicans Candida spp. in the neonatal ICU may lead to a preponderance of C. tropicalis as a significant cause of neonatal fungemia