Manish Butte

Synchronous Primary Central Nervous System and Pulmonary Lymphoma in a 7-Year-Old Female with Unspecified T-Cell Immunodeficiency.

Pediatr Neurosurg. 2018 Aug 15;:1-6

Authors: Ghali MGZ, Samkari A, Hou JS, Balasubramanian M, Besmer S, Keisling M, Narayan P

Abstract
Primary central nervous system lymphoma (PCNSL) is rare in children with immunocompromise as an important risk factor. A 7-year-old girl with unspecified T-cell immunodeficiency presented with left-sided weakness and was found to have a right-sided frontal lobe mass on imaging. The mass was resected; histopathology and molecular studies evidenced diffuse large B-cell lymphoma. Prior chest imaging had revealed left upper lobe mass, and repeat chest imaging revealed multiple pulmonary nodules, initially concerning for metastasis. Video-assisted thoracoscopic surgical wedge resection of the lung mass was performed; the molecular profile was distinct from the PCNSL, suggesting synchronous de novo lymphomagenesis of brain and pulmonary primaries.

PMID: 30110687 [PubMed – as supplied by publisher]

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Monogenic Intestinal Epithelium Defects and the Development of Inflammatory Bowel Disease.

Physiology (Bethesda). 2018 Sep 01;33(5):360-369

Authors: Leung G, Muise AM

Abstract
The incidence of inflammatory bowel disease (IBD) is increasing worldwide, most notably in young children. The development of disease is a combination of several factors, including genetics, environment, the microbiota, and immune system. Recently, next-generation sequencing has allowed for the identification of novel genetic causes for intestinal disease, including pediatric inflammatory bowel disease (IBD). These IBD genes can generally be grouped into genes causing either primary immunodeficiency or intestinal epithelial defects (the focus of this review). Most of these genes have been functionally validated with in vitro and/or animal models, and have been demonstrated to cause intestinal disease. Intestinal epithelial IBD genes are of particular interest since they are the least amenable to current therapies; therefore, further research is warranted to develop potential therapies. A number of cellular pathways are impacted with intestinal epithelial IBD genes, including intestinal epithelial cell adhesion and generation of reactive oxygen species. Here, we describe the currently known IBD risk alleles and monogenic causal intestinal epithelial genes, their putative roles in preserving intestinal epithelial cell homeostasis, and their implications for IBD pathophysiology.

PMID: 30109822 [PubMed – in process]

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Monogenic polyautoimmunity in primary immunodeficiency diseases.

Autoimmun Rev. 2018 Aug 11;:

Authors: Azizi G, Yazdani R, Rae W, Abolhassani H, Rojas M, Aghamohammadi A, Anaya JM

Abstract
Primary immunodeficiency diseases (PIDs) consist of a large group of genetic disorders that affect distinct components of the immune system. PID patients are susceptible to infection and non-infectious complications, particularly autoimmunity. A specific group of monogenic PIDs are due to mutations in genes that are critical for the regulation of immunological tolerance and immune responses. This group of monogenic PIDs is at high risk of developing polyautoimmunity (i.e., the presence of more than one autoimmune disease in a single patient) because of their impaired immunity. In this review, we discuss the mechanisms of autoimmunity in PIDs and the characteristics of polyautoimmunity in the following PIDs: IPEX; monogenic IPEX-like syndrome; LRBA deficiency; CTLA4 deficiency; APECED; ALPS; and PKCδ deficiency.

PMID: 30107266 [PubMed – as supplied by publisher]

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Primary İmmunodeficiency Brings a Burden to Child’s Psychological Condition.

Pediatr Int. 2018 Aug 13;:

Authors: Kayan Ocakoglu B, Karaca NE, Ocakoğlu FT, Erermis S

Abstract
BACKGROUND: Primary immunodeficiencies (PIDs) are such a chronic disorder may increase the prevalence of psychopathologies. There is sparse of studies which investigate the psychopathology and disease-related factors’ effect on psychopathology in this population.
OBJECTIVES: We aimed to assess and compare children with PIDs, who receive intravenous immunoglobulin treatment, Juvenile Idiopathic Arthritis (JIA) and healthy controls with respect to their mental health status.
METHODS: Forty-four children with PID, 32 children with JIA and 30 healthy controls, were evaluated by psychiatric evaluation. Childhood Depression Inventory, and Screen for Child Anxiety-Related Emotional Disorders questionnaire were filled by participants. Children Behavior Checklist also was completed by mothers of participants. In addition, disease-related factors identified.
RESULTS: The frequency of mood disorders among these three groups were detected differently. There was no difference between the groups of PID and JIA with respect to the prevalence of mood disorders and other psychopathologies. The disease-related factors were found associated with the frequency of mood disorder in PIDs patients.
CONCLUSION: As a conclusion, the rate of psychopathology found similar in patients with PIDs and JIA and higher than the controls. Some of the disease-related factors were found associated with the frequency of mood disorders in patients with PIDs. This article is protected by copyright. All rights reserved.

PMID: 30103264 [PubMed – as supplied by publisher]

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IgA Deficiency and Nephrotic Syndrome in Children.

Int J Environ Res Public Health. 2018 Aug 09;15(8):

Authors: Di Genova L, Ceppi S, Stefanelli M, Esposito S

Abstract
Background: Imunoglobulin A (IgA) deficiency (IgAD) is the most common form of primary immunodeficiency in Western countries. There have been several reports on IgAD complicated by glomerulonephritis in adults, but only very few cases of IgAD with nephropathy have been reported in children. We present two cases of IgAD with relapsing nephrotic syndrome in pediatric age. Case presentation: A 4-year-old boy and a 2-year-old boy presented with bilateral periorbital oedema and weight gain. The results of laboratory tests revealed IgAD (IgA < 7 mg/dL), normal creatinine, hypoprotidaemia, hypoalbuminaemia, and nephrotic proteinuria. A diagnosis of IgAD and idiopathic nephrotic syndrome was made, and steroid treatment (prednisone 60 mg/mq/day) was started. During steroid tapering, the children experienced several relapses and to obtain a positive outcome they required therapy with human monoclonal anti-CD20 antibodies (rituximab in the first child, ofatumumab in the second one). Conclusions: Our cases highlight that IgAD can be observed in nephrotic syndrome and nephropathy in children with IgAD appears to be complicated and difficult to treat with corticosteroids alone. Further research is needed to better describe the clinical manifestations and pathological pictures among subjects with IgAD and nephrotic syndrome to understand whether IgAD has a prognostic value in children with nephrotic syndrome and to let clinical physicians define a more personalized and appropriate approach for the management of these patients.

PMID: 30096909 [PubMed – in process]

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Human hyper-IgE syndrome: singular or plural?

Mamm Genome. 2018 Aug 09;:

Authors: Zhang Q, Boisson B, Béziat V, Puel A, Casanova JL

Abstract
Spectacular progress has been made in the characterization of human hyper-IgE syndrome (HIES) over the last 50 years. HIES is a primary immunodeficiency defined as an association of atopy in a context of very high serum IgE levels, characteristic bacterial and fungal diseases, low-level clinical and biological inflammation, and various non-hematopoietic developmental manifestations. Somewhat arbitrarily, three disorders were successively put forward as the underlying cause of HIES: autosomal dominant (AD) STAT3 deficiency, the only disorder corresponding to the original definition of HIES, and autosomal recessive (AR) DOCK8 and PGM3 deficiencies, in which atopy and high serum IgE levels occur in a context of manifestations not seen in patients with typical HIES. Indeed, these three disorders disrupt different molecular pathways, affect different cell types, and underlie different clinical phenotypes. Surprisingly, several other inherited inborn errors of immunity in which serum IgE levels are high, sometimes almost as high as those in HIES patients, are not considered to belong to the HIES group of diseases. Studies of HIES have been further complicated by the lack of a high serum IgE phenotype in all mouse models of the disease other than two Stat3 mutant strains. The study of infections in mutant mice has helped elucidate only some forms of HIES and infection. Mouse models of these conditions have also been used to study non-hematopoietic phenotypes for STAT3 deficiency, tissue-specific immunity for DOCK8 deficiency, and cell lineage maturation for PGM3 deficiency. We review here the history of the field of HIES since the first clinical description of this condition in 1966, together with the three disorders commonly referred to as HIES, focusing, in particular, on their mouse models. We propose the restriction of the term “HIES” to patients with an AD STAT3-deficiency phenotype, including the most recently described AR ZNF341 deficiency, thus excluding AR DOCK8 and PGM3 deficiencies from the definition of this disease.

PMID: 30094507 [PubMed – as supplied by publisher]

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Jakinibs for the Treatment of Immunodysregulation in Patients with Gain of Function STAT1 or STAT3 Mutations.

J Allergy Clin Immunol. 2018 Aug 06;:

Authors: Forbes LR, Vogel TP, Cooper MA, Castro-Wagner J, Schussler E, Weinacht KG, Plant AS, Su HC, Allenspach EJ, Slatter M, Abinun M, Lilic D, Cunningham-Rundles C, Eckstein O, Olbrich P, Guillerman RP, Patel NC, Demirdag YY, Zerbe C, Freeman AF, Holland SM, Szabolcs P, Gennery A, Torgerson TR, Milner JD, Leiding JW

Abstract
Treatment of the autoimmune and immune-dysregulatory features of patients with STAT1 GOF or STAT3 GOF disease remains challenging. Jakinibs have been used to treat the severe immune-dysregulation in patients with either STAT1 GOF or STAT3 GOF mutations.

PMID: 30092289 [PubMed – as supplied by publisher]

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Validation of calculated globulin (CG) as a screening test for antibody deficiency in an Italian University Hospital.

Curr Pharm Biotechnol. 2018 Aug 08;:

Authors: Pecoraro A, Jolles S, Crescenzi L, Varricchi G, Marone G, Savoia M, Genovese A, Spadaro G

Abstract
Morbidity and mortality of primary and secondary antibody deficiencies (AD) are frequently associated with diagnostic delays. These could be avoided by a combination of factors including a widespread and effective development in screening tests. Calculated globulin (CG), derived from the difference between serum total protein and albumin levels, reflects immunoglobulin serum levels and has shown to have a predictive value in the early diagnosis of antibody deficiencies. This study investigated the possibility to use low levels of CG to detect antibody deficiency in an Italian University Hospital. First, we conducted an analysis of anonymized adult samples collected at our biochemistry laboratory with a range of calculated globulin levels from 15 to 22 g/l. A CG cut-off of 19 g/l detected subjects with IgG lower than 600 mg/dl with a sensitivity of 70% and a specificity of 75%. To further verify the clinical usefulness of CG, we retrospectively evaluated the relationship between CG values and serum IgG levels in 38 patients diagnosed with CVID at our Institution. Using a CG cut-off of 19 g/l we detected antibody deficiency in 97.3% (37/38) of the subjects present in our cohort. Finally, we chose a CG value of 19 g/l as cut-off for a prospective AD screening program. The results of this study show that a screening CG test can be used as a tool to reduce diagnostic delays, improve long-term prognosis and reduce the healthcare costs of antibody deficiency.

PMID: 30091407 [PubMed – as supplied by publisher]

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Intravenous immunoglobulin 10% in children with primary immunodeficiency diseases.

Immunotherapy. 2018 Aug 08;:

Authors: Ochs HD, Melamed I, Borte M, Moy JN, Pyringer B, D Kobayashi AL, Knutsen AP, Smits W, Pituch-Noworolska A, Kobayashi RH

Abstract
AIM: To assess the safety and efficacy of an intravenous immunoglobulin (IVIG) 10% preparation (Panzyga®; Octapharma AG, Lachen, Switzerland) in predominantly antibody-deficient children with primary immunodeficiency disease.
METHODS: Data from two prospective, open-label and noncontrolled multicenter Phase III studies of IVIG 10% that included 25 patients <16 years of age were analyzed for efficacy, pharmacokinetics and safety.
RESULTS: The rate of serious bacterial infections was 0.04/patient-year. A maximal infusion rate of 0.14 ml/kg/min was achieved in 82% of pediatric patients (n = 9). Infusions of immunoglobulin G trough levels between infusions remained ≥5-6 g/l; median half-life was 32.79-36.62 days. Abdominal pain, headache and chills were the most common treatment-related adverse events.
CONCLUSION: IVIG 10% is safe and effective for the treatment of predominantly antibody-deficient children.

PMID: 30088423 [PubMed – as supplied by publisher]

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Surgical Resection Of Thoracic Aortic Aneurysms In Wiskott-Aldrich Syndrome.

Heart Surg Forum. 2018 Jul 02;21(4):E305-E306

Authors: Onalan MA, Sayin OA, Tireli E

Abstract
Aortic aneurysms are a rare condition in children. Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by infections, thrombocytopenia, and eczema. Aortitis and aneurysm formation seem to be progressive in patients with Wiskott-Aldrich syndrome. The risk of death from aneurysmal rupture in patients with Wiskott-Aldrich syndrome is high and surgery is required for resection of aneurysms. We report a case where a successful resection of a descending thoracic aneurysm. We present a-12 year-old child with this syndrome who underwent a one-stage descending aortic aneurysm repair under continuous visceral perfusion.Histologic examination showed the presence of an aortitis withgranulomatous inflammatory response and multinucleated cells.

PMID: 30084784 [PubMed – in process]

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