Research

Ataxia telangiectasia associated with nodular regenerative hyperplasia.

J Clin Immunol. 2016 Sep 26;

Authors: Milligan KL, Schirm K, Leonard S, Hussey AA, Agharahimi A, Kleiner DE, Fuss I, Lingala S, Heller T, Rosenzweig SD

PMID: 27671921 [PubMed – as supplied by publisher]

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Eltrombopag (thrombopoietin-receptor agonist) and plasmapheresis as rescue therapy of acute post-renal transplant immune thrombocytopenia in a child with Schimke immuno-osseous dysplasia-case report.

Pediatr Transplant. 2016 Sep 26;

Authors: Grenda R, Jarmużek W, Latoszyńska J, Prokurat S, Rubik J

Abstract
SIOD is rare disorder related to SMARCAL1 or SMARCAL2 gene mutation, including (among other comorbidities) T-cell immunodeficiency, nephrotic syndrome, and renal failure. Up to 22% of primary patients may develop various autoimmune disorders. We report the case of 11-year-old male with SIOD, who presented ITP at 2 years after renal transplantation with decrease in platelet count (from normal) to 56 000/μL and then (gradually) to 2000/μL. There was no effect of iv. methylprednisolone/dexamethasone. As the presence of antibodies against GPIIb/IIIa, GPIb, and GPIaIIa platelet glycoproteins was confirmed, patient was given 50 g of IVIG and then was put on plasmapheresis; however, both showed poor direct effect. As we were afraid to give rituximab (due to expected overimmunosuppression), we prescribed the oral TPO-receptor agonist (eltrombopag). Patient responded after 17 days of therapy, to the final dose of 50 mg/d (approx. 2 mg/kg). The antiplatelet antibodies disappeared after four plasmapheresis. Overall, the therapy was continued for 7 weeks and was stopped at platelet count of 433 000/μL. Platelet count remained stable in 8-month follow-up. Combination of plasmapheresis and TPO-receptor agonist was effective in post-renal transplant acute ITP in patient with SIOD.

PMID: 27671102 [PubMed – as supplied by publisher]

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A novel missense mutation in the NADPH binding domain of CYBB abolishes the NADPH oxidase activity in a male patient with increased susceptibility to infections.

Microb Pathog. 2016 Sep 22;

Authors: Khan TA, Kalsoom K, Iqbal A, Asif H, Rahman H, Farooq SO, Naveed H, Nasir U, Amin MU, Hussain M, Tipu HN, Florea A

Abstract
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the five structural genes (CYBB, CYBA, NCF1, NCF2, and NCF4) that typically results in a decrease in function or inability to generate a respiratory burst, leading to defective killing of pathogens, including fungi and intracellular bacteria. Mutations in CYBB, encoding the gp91phox (also known as NOX2) result in X-linked CGD account for approximately 65% of CGD cases. Here, we aimed the characterization of a novel missense mutation c.1226C > A/p.A409E in the CYBB gene in a patient with X-linked CGD. Relevant clinical data of a male patient whose family was positive for XCGD was reviewed. Oxidative burst and NADPH protein expression was evaluated by flow cytometry, while Genetic analysis was performed by Sanger sequencing. Monocyte-derived macrophages (MDMs) were evaluated for their capacity for phagocytosis and growth suppression of the intracellular Mycobacterium tuberculosis (M. tuberculosis). We thus report the absence of an oxidative burst in the phagocytes of the patient. Flow cytometry evaluation revealed a normal expression of NADPH oxidase components in neutrophils and genetic analysis proved the existence of a novel missense c.1226C > A mutation in the CYBB gene resulting in p.A409E. Further, we have showed that the patient’s MDMs were unhindered in their ability to take up mycobacteria normally. Instead, the MDMs failed to control the intracellular proliferation of M. tuberculosis, a phenotype that improved in the presence of recombinant human interferon-gamma (rhIFN-γ). This work expands the genetic spectrum of X-linked CGD and demonstrates improvement in macrophage function in X + CGD patient by rhIFN-γ.

PMID: 27666509 [PubMed – as supplied by publisher]

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Impaired Akt phosphorylation in B-cells of patients with common variable immunodeficiency.

Clin Immunol. 2016 Sep 21;

Authors: Yazdani R, Ganjalikhani-Hakemi M, Esmaeili M, Abolhassani H, Vaeli S, Rezaei A, Sharifi Z, Azizi G, Rezaei N, Aghamohammadi A

Abstract
Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency characterized by recurrent infectious. We evaluated whether defective PI3K/Akt/FoxO pathway could influence B-cell fate. Determination of B-cell subsets in CVD patients and healthy donors (HDs) were performed using flow cytometry. We evaluated mRNA level and protein expression of PI3K, Akt and FoxO molecules using real-time PCR and flow cytometry, respectively. Moreover, phosphorylated Akt (p-Akt) expression in B-cells has also been measured by flowcytometry. We identified a significant reduction in percentage of marginal zone like B-cells, Switched and unswitched memory B-cells, total memory B-cells and plasmablasts in patients, as these reductions of had significantly negative correlation with increased apoptosis in patients. Surprisingly, we identified decreased p-AKT expression in B-cells of patients than HDs. We describe for the first time impaired p-Akt expression in B-cells of CVID patients that had a significant correlation with antibody response to vaccine and clinical manifestations.

PMID: 27664934 [PubMed – as supplied by publisher]

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Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia.

Neuromolecular Med. 2016 Sep 23;

Authors: Carranza D, Vega AK, Torres-Rusillo S, Montero E, Martinez LJ, Santamaría M, Santos JL, Molina IJ

Abstract
Ataxia-telangiectasia is a multisystemic disease with severe neurological affectation, immunodeficiency and telangiectasia. The disorder is caused by alterations in the ATM gene, whose size and complexity make molecular diagnosis difficult. We designed a target-enrichment next-generation sequencing strategy to characterize 28 patients from several regions of Spain. This approach allowed us to identify gene variants affecting function in 54 out of the 56 alleles analyzed, although the two unresolved alleles belong to brothers. We found 28 ATM gene mutations, of which 10 have not been reported. A total of 171 gene variants not affecting function were also found, of which 22 are reported to predispose to disease. Interestingly, all Roma (Spanish Gypsies) patients are homozygous for the same mutation and share the H3 ATM haplotype, which is strong evidence of a founder effect in this population. In addition, we generated a panel of 27 primary T cell lines from A-T patients, which revealed significant expression of ATM in two patients and traces of the protein in nine more. None of them retained residual ATM activity, and almost all T cell lines show increased or intermediate radiosensitivity.

PMID: 27664052 [PubMed – as supplied by publisher]

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Clinical and imaging considerations in primary immunodeficiency disorders: an update.

Pediatr Radiol. 2016 Sep 22;

Authors: Wu EY, Ehrlich L, Handly B, Frush DP, Buckley RH

Abstract
Primary immunodeficiencies are a group of genetically determined disorders with diverse presentations. The purpose of this review is to provide a practical and brief description of a select number of these diseases and to discuss the important role the radiologist can have in making an early diagnosis and in detecting and following disease complications. The role of diagnostic imaging and informed performance and interpretation are vital in the diagnosis, surveillance and management of all primary immunodeficiency disorders.

PMID: 27655432 [PubMed – as supplied by publisher]

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Anxiety and depression in adults with primary immunodeficiency: How much do these patients experience and how much do they attribute to their primary immunodeficiency?

Allergy Asthma Proc. 2016 Sep;37(5):409-415

Authors: Heath J, Lehman E, Saunders EF, Craig T

Abstract
INTRODUCTION: Primary immunodeficiency (PID) is a rare group of disorders that manifest similarly with infection, neoplasms, allergic, and autoimmune diseases, and are treated with injectable medications. Often the burden of disease and cost of management is excessive, and premature death is not uncommon. In light of these features of PID, it was our objective to survey our cohort to assess for factors that can influence depression and anxiety.
METHODS: We used an investigator-developed survey, in addition to the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale, after institutional review board approval of our pilot study, to determine the extent of anxiety and depression that our patients with PID experienced and variables that may have affected the difference of expression. The differences among groups were tested by using Wilcoxon rank sum tests, Kruskal-Wallis tests, and chi-square tests.
RESULTS: The patients with PID had similar depression compared with the U.S. population, as assessed by the HAM-D scale. Risk factors associated with elevated HAM-D scores included the following: not driving, intravenous immunoglobulin therapy (versus subcutaneous), nurse-administered therapy (versus self-administered), having unpleasant adverse effects from therapy, previously attempted suicide, and family members with reported anxiety and/or depression. Anxiety was not significantly increased in our cohort. Risk factors for significantly elevated Hamilton Anxiety Rating Scale scores included the following: having poor health, an unhealthy diet, lack of refreshing sleep, and family members with reported anxiety and/or depression.
CONCLUSION: Many factors influence depression and anxiety, and may add to the morbidity of PID. Patients should be assessed for our identified factors for depression and anxiety. Treatment or referrals should be initiated as it is hoped to improve our patients’ quality of life and outcomes.

PMID: 27657526 [PubMed – as supplied by publisher]

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Disseminated bacille Calmette-Guérin disease in Saudi children: clinical profile, microbiology, immunology evaluation and outcome.

Eur Rev Med Pharmacol Sci. 2016 Sep;20(17):3696-3702

Authors: Bukhari E, Alaklobi F, Bakheet H, Alrabiaah A, Alotibi F, Aljobair F, Alshamrani M, Alaki E, Alnahdi F, Alodyani A, Alzamil F

Abstract
OBJECTIVE: The bacille Calmette Guérin (BCG) vaccine is administered worldwide to prevent tuberculosis. Although, Post BCG vaccination complications like disseminated BCG infections are rare and immunocompromised children are at high risk of developing BCG-related complications including BCG-lymphadenitis and other disseminated diseases.
PATIENTS AND METHODS: This was a prospective study of children who developed disseminated BCG after vaccination who were admitted in three tertiary care hospital in Riyadh, Saudi Arabia, in the year 2015. The clinical presentation, microbiological/immunological evaluation and outcome will be discussed.
RESULTS: 12 cases (7 males and 5 females) of disseminated BCG infections after vaccination were documented with age ranges 3 and 32 months. Eight (66%) patients had interleukin IL-12 deficiency and 3 (25%) had severe combined immune deficiency (SCID) and 1 (8%) had Interferon gamma receptor II deficiency. 9 (75%) patients presented with generalized lymphadenopathy. Hepatosplenomegaly was present in 6 (50%) patients. 2 (16%) patients presented with a recurrent skin infection and persistent oral candidiasis in one patient and pneumonia in the other. Five (41%) families were from 1st degree consanguineous marriage. Tuberculosis (TB) culture and sensitivity were positive for Mycobacterium bovis from gastric aspirate (GA) in 4 patients and the lymph node in 9 patients and 1 patient had culture positive from both skin lesion and lymph nodes. Mycobacterium bovis PCR was positive in 4 patients. All patients received anti-tuberculosis therapy; all patients survived except one who died due to multi-organ failure.
CONCLUSIONS: These results indicate that the prevalence of disseminated BCG vaccine in immunocompromised Saudi children is significantly high. Since in our region we have a high consanguinity rate and a high number of primary immune deficiency disorder (PID), we believe that BCG vaccination should be postponed till a child reaches one-year-old and appropriate tests exclude the diagnosis of primary immunodeficiency diseases.

PMID: 27649674 [PubMed – as supplied by publisher]

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[Clinical characteristics and etiology of children with hypereosinophilia].

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2016 May 25;45(3):292-296

Authors: Xiaohong C, Yiping XU, Meiping LU

Abstract
Objective: To analyze the clinical characteristics and etiology of hypereosinophilia in children. Methods: Clinical data of 88 children with hypereosinophilia admitted in Children’s Hospital of Zhejiang University School of Medicine during April 2009 and May 2015 were retrospectively reviewed. The clinical manifestations, etiologies, and the correlation of disease severity with different etiologies were analyzed. Results: The main clinical manifestations were fever, abdominal pain, cough and/or tachypnea, skin rash, hemafecia and diarrhea, which were observed in 19 (21.6%), 15 (17.0%), 14 (15.9%), 13 (14.8%), 11 (12.5%) and 6 (6.8%) cases, respectively. For etiologies, there were 28 cases (31.8%) induced by infections, including 11 cases of acute bronchial pneumonia, 9 cases of parasite infection, 4 cases of septicemia, 2 cases of urinary system infection, 1 case of cellulitis and 1 case of cholecystitis complicated with pancreatitis. The etiologies for the rest cases were allergic diseases (25 cases, 28.4%), eosinophilic gastroenteritis (20 cases, 22.7%), immunodeficiency (3 cases, 3.4%, all were moderate to severe eosinophilia), ABO hemolysis (2 cases, 2.3%), hematologic neoplasms (2 cases, 2.3%), eosinophilic cystitis (1 case, 1.1%), eosinophilic granulomatosis with polyangitis (1 case, 1.1%), nephrotic syndrome (1 case, 1.1%), and 5 cases (5.7%) were of unknown causes. Conclusions: Fever, abdominal pain, cough and/or tachypnea are the most common clinical manifestations in children with hypereosinophilia. Infection, allergic diseases and eosinophilic gastroenteritis are the most common etiologies, and parasites are the most common pathogen identified. Differential diagnosis of primary immunodeficiency should be considered in children with moderate to severe eosinophilia.

PMID: 27651195 [PubMed – as supplied by publisher]

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