Research

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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Genetic Analysis of Patients with Two Different Types of Hyper IgM Syndrome.

Immunol Invest. 2018 Aug 06;:1-9

Authors: Alizadeh Z, Mazinani M, Houshmand M, Shakerian L, Nourizadeh M, Pourpak Z, Fazlollahi MR

Abstract
BACKGROUND: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections.
OBJECTIVES: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients.
METHODS: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies. Sanger sequencing was applied to detect pathogenic mutations in CD40L and AID genes causing two most common forms of HIGM, which known as HIGM type 1 and 2, respectively.
RESULTS: All patients who entered the study were males from unrelated families with a median age of 3.8 years. The most frequent clinical manifestation was recurrent pneumonia. Genetic studies of the patients revealed six different mutations, including five mutations in CD40L besides one mutation in AID. Two mutations in CD40L (p.F31fsX5 and p.C84S) were novel and three mutations (p. G219R, p.D62fsX18, and p.Q186X) have been previously reported. The mutation found in AID (p.E122X) was also previously described.
CONCLUSION: The study results may provide valuable information for prenatal diagnosis and also for genetic counseling especially for those who have a history of primary immunodeficiency in their family.

PMID: 30081731 [PubMed – as supplied by publisher]

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[EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

Harefuah. 2017 Nov;156(11):705-709

Authors: Shostak Y, Kramer MR

Abstract
INTRODUCTION: Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients’ quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

PMID: 29198088 [PubMed – indexed for MEDLINE]

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Long-term follow-up of an Activated PI3K-δ Syndrome 2 patient presenting with an agammaglobulinemia phenotype.

Ann Allergy Asthma Immunol. 2018 Aug 03;:

Authors: Yann N, Jérémie R, Claire A, Capucine P, Marion M

PMID: 30081089 [PubMed – as supplied by publisher]

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[Spondyloenchondrodysplasia with immune dysregulation: a case report and literature review].

Zhonghua Er Ke Za Zhi. 2018 Aug 02;56(8):611-616

Authors: Zhong LQ, Wang L, Song HM, Wang W, Wei M, He YY

Abstract
Objective: To analyze the clinical characteristics of spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Methods: The clinical manifestations, laboratory examinations, treatment and genetic analysis of a patient diagnosed with SPENCDI who was admitted to the Department of Pediatrics in Peking Union Medical College Hospital in October 2016 were analyzed. Then literature review was done after searching articles in PubMed and several Chinese databases with the key words “spondyloenchondrodysplasia with immune dysregulation” up to the date of November 2017. Results: A 12-year-old girl was admitted to local hospital for complaint of “recurrent fever over one month” in October 2016. She was diagnosed with type Ⅱ autoimmune hepatitis for abnormal liver function, elevated immunoglobulin G, positive anti-liver-kidney microsomal antibody and medium to severe interface hepatitis verified by liver biopsy. Systemic lupus erythematosus was also suspected based on positive antinuclear antibody and anti-dsDNA antibody, decreased complements, reduced white blood cells and hemoglobin. Methylprednisolone and azathioprine were started based on the diagnosis. However, she experienced mycoplasma pneumoniae and suspected fungal infections during the treatment. Detailed history revealed the history of developmental retardation since birth, and cerebral palsy diagnosed when she was 2 years old. She also underwent surgery at the age of eight for eversion of her right foot. Based on the abnormal findings of immune system, skeleton and nervous system, certain primary immunodeficiency disease was speculated. Gene sequencing was performed, which revealed compound heterozygous mutations in ACP5 gene (NM_001111035.2) (c.798dupC, p. S267Lfs*20, paternal; c.716G>A, p. G239D, maternal). With X-ray of the vertebrae showed multiple platyspondyly, the diagnosis was corrected as SPENCDI and type Ⅱ autoimmune hepatitis. Then she was treated with prednisone (60 mg/d) and mycophenolate mofetil (1.5 g/d). All symptoms resolved on 3-month follow-up, with normalized activity indexes of autoimmune hepatitis and systemic lupus erythematosus. A total of 25 articles (1 Chinese, 24 English) were reviewed, with 74 SPENCDI patients reported. The most common manifestations were skeletal abnormalities (74/74, 100%), autoimmune diseases (47/74, 63.5%), dwarfism (45/74, 60.8%), and nervous system symptoms (25/74, 33.8%). A few patients with simple spondyloenchondrodysplasia were treated with growth hormone, and those who with autoimmune diseases were treated with immunosuppressants, all of whom were improved to certain extent. Conclusions: Vertebral and metaphyseal dysplasia, nervous system symptoms, and strong predisposition to autoimmune diseases are the hallmarks of SPENCDI. SPENCDI should be considered in dwarf with or without autoimmune diseases or nervous system symptoms.

PMID: 30078244 [PubMed – in process]

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Outcome of continuous renal replacement therapy in critically ill children: a retrospective cohort study.

Ann Saudi Med. 2018 Jul-Aug;38(4):260-268

Authors: Al-Ayed T, Rahman NU, Alturki A, Aljofan F

Abstract
BACKGROUND: Continuous renal replacement therapy (CRRT) has become the preferred mode of dialysis to support critically ill children with acute kidney injury. However, there are limited pediatric data on CRRT use, especially in our region.
OBJECTIVE: Determine the outcome of CRRT among critically ill children.
DESIGN: Retrospective cohort study.
SETTING: Pediatric intensive care unit.
PATIENTS AND METHODS: The study included critically ill children 1-14 years of age who underwent CRRT from July 2009 to June 2015. We report the underlying diagnosis, demographics, indications and modality of CRRT, and associated risk factors. Statistical analyses were used to identify risk factors associated with mortality.
MAIN OUTCOME MEASURES: Mortality and associated risk factors with use of CRRT.
SAMPLE SIZE: 96 RESULTS: The mean age was 6.0 (standard deviation, 4.4) years, with a male preponderance in the age group from 1-10 years which comprised almost 60% of the study group. The most common primary diagnoses were malignancies [37.5% (36/96)] followed by primary renal diseases [19.8% (19/96)], and immunodeficiency [16.7% (16/96)]. The most common indication for CRRT was fluid overload [67.2% (65/96)] followed by tumor lysis syndrome [18.8%(18/96)], and metabolic encephalopathy [9.4%(9/96)]. The median length of CRRT was 66 hours (IQR, 35.5-161.4), with a median average circuit life of 30.9 hours (IQR, 16.4-45.0). The most common CRRT catheter site was the internal jugular vein [77.1% (74/96)], followed by the femoral vein [18.8%(18/96)] with continuous venovenous hemodiafiltration [82.3%(79/96)] being the most common CRRT modality used. The mortality rate among critically ill children requiring CRRT was 50% (48/96). There was an increased mortality rate among children with hematological diseases (100%, 10/10), immunodeficiency (86.6%, 13/16) and in children who had undergone stem cell transplantation (90.0%, 27/30), with the least mortality in primary renal disease (15.8% (3/19). We identified septic shock and use of inotropic support as being independently associated with mortality in a multivariate analysis.
CONCLUSION: The overall mortality rate among critically ill children who un.derwent CRRT was 50% with significantly increased mortality among patients with hematological diseases, immunodeficiency, and in children who had undergone stem cell transplantation. Septic shock and use of inotropic support were associated with mortality.
LIMITATIONS: Retrospective and single center data that is not generalizable.
CONFLICT OF INTEREST: None.

PMID: 30078024 [PubMed – in process]

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Deficiencies in the CD19 complex.

Clin Immunol. 2018 Jul 31;:

Authors: Wentink MWJ, van Zelm M, van Dongen JJM, Warnatz K, van der Burg M

Abstract
Signaling via the CD19-complex, consisting of CD19, CD81, CD21 and CD225, is critically important for B-cell development, differentiation and maturation. In this complex, each protein has its own distinct function. Over the past decade, 15 patients with antibody deficiency due to deficiencies in the CD19-complex have been described. These patients have deficiencies in different complex-members, all caused by either homozygous or compound heterozygous mutations. Although all patients had antibody deficiencies, the clinical phenotype was different per deficient protein. We aimed to provide an overview of what is known about the function of the different complex-members, knowledge from mouse-studies and to summarize the clinical phenotypes of the patients. Combining this knowledge together can explain why deficiencies in different members of the same complex, result in disease phenotypes that are alike, but not the same.

PMID: 30075290 [PubMed – as supplied by publisher]

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Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4+Foxp3+ Regulatory T Cells Differentiation.

Front Immunol. 2018;9:1662

Authors: Chen W, Wang J, Xu Z, Huang F, Qian W, Ma J, Wee HB, Lewis GS, June RR, Schafer PH, Lin J, Zheng SG

Abstract
Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4+Foxp3+ regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency mouse model of RA were used to study the role of Apremilast in the suppression of RASF-mediated cartilage destruction in vivo. Compared with untreated and vehicle control groups, we found that Apremilast therapy delayed arthritis onset and reduced arthritis scores in the CIA model. Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in the Apremilast treatment groups. Moreover, Apremilast markedly prevented the development of bone erosions in CIA mice by CT analysis. Furthermore, in the Apremilast treated group, the frequency of Th17 cells and Th1 cells was significantly decreased while Treg cells’ frequency was significantly increased. The high dose of Apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA. Apremilast treatment reduced the migratory ability of RASFs and their destructive effect on cartilage. Compared with the model group, Apremilast treatment significantly reduced the RASFs invasion cartilage scores in both primary implant and contralateral implant models. Our data suggest that Apremilast is effective in treating autoimmune arthritis and preventing the bone erosion in the CIA model, implicating its therapeutic potential in patients with RA.

PMID: 30072998 [PubMed]

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Is an infectious trigger always required for primary hemophagocytic lymphohistiocytosis? Lessons from in utero and neonatal disease.

Pediatr Blood Cancer. 2018 Aug 01;:e27344

Authors: Heeg M, Ammann S, Klemann C, Panning M, Falcone V, Hengel H, Lehmberg K, Zur Stadt U, Wustrau K, Janka G, Ehl S

Abstract
In this report, we evaluate the hypothesis that hemophagocytic lymphohistiocytosis in patients with defects of lymphocyte cytotoxicity is usually triggered by infections. We show that in the majority of patients, extensive virus PCR panels performed in addition to routine microbiological investigations remain negative and summarize 25 patients with onset of hemophagocytic lymphohistiocytosis in utero or within the first 10 days of life, in none of which an associated bacterial or viral infection was reported. These observations, even though preliminary, invite to consider a key role of lymphocyte cytotoxicity in controlling T-cell homeostasis also in the absence of apparent infectious stimuli.

PMID: 30070073 [PubMed – as supplied by publisher]

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[Primary central nervous system methotrexate associated lymphoproliferative disorders in a patient with rheumatoid arthritis].

Rinsho Shinkeigaku. 2018 Jul 31;:

Authors: Uchida Y, Hokkoku K, Hatanaka Y, Kikuchi Y, Tashiro H, Sonoo M

Abstract
We report on a 52-year-old woman with rheumatoid arthritis (RA) who developed methotrexate associated lymphoproliferative disorders (MTX-LPD) in the central nervous system (CNS) in the course of immunosuppressive therapy for RA. The patient was admitted because of monoplegia in her left hand. She had been receiving methotrexate (MTX) for her RA for several years and etanercept had also been introduced because of a worsening of the arthritis six months before admission. Brain MRI revealed multiple lesions with enhancement scattered throughout both hemispheres. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography showed abnormal accumulation suggesting malignancy in the right frontal lobe where abnormal enhancement was observed on the MRI. A brain biopsy was performed at the identified site and it confirmed diffuse large B-cell lymphoma (DLBCL). We therefore diagnosed her as MTX-LPD. According to previous reports, most MTX-LPD cases tend to show regression after the cessation of MTX. However, our case showed no regression and even needed chemotherapy. The patient had a poorer prognosis than previous cases and died 17 months after the onset. Although it is an uncommon complication, particularly in the CNS, MTX-LPD should be considered as a critical differential diagnosis if a patient receiving MTX develops central nervous system lesions. Immediate medical intervention including brain biopsy is required.

PMID: 30068810 [PubMed – as supplied by publisher]

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