Manish Butte

IL-12 receptor 1β deficiency with features of autoimmunity and photosensitivity.

Autoimmunity. 2016 Jan 13;:1-4

Authors: Ling G, Ling E, Broides A, Poran Feldman H, Levy J, Garty BZ, Nahum A

Abstract
Primary immunodeficiences are often accompanied by autoimmune phenomena. IL-12 receptor deficiency is a well characterized primary immunodeficiency that leads to propensity to intracellular infections mainly with mycobacteria and Salmonella. We report on two patients with IL-12 receptor β1 deficiency that presented with autoimmune manifestations and photosensitivity dermatitis and describe possible pathogenetic mechanisms leading to development of clinically significant autoimmune phenomena.

PMID: 26761636 [PubMed – as supplied by publisher]

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Primary Pulmonary Lymphoid Lesions: Radiologic and Pathologic Findings.

Radiographics. 2016 Jan-Feb;36(1):53-70

Authors: Sirajuddin A, Raparia K, Lewis VA, Franks TJ, Dhand S, Galvin JR, White CS

Abstract
The pulmonary lymphoid system is complex and is composed of two compartments: the pulmonary lymphatics and the bronchus-associated lymphoid tissue (BALT). Additional important cells that function in the pulmonary lymphoid system include dendritic cells, Langherhans cells, macrophages, and plasma cells. An appreciation of the normal lymphoid anatomy of the lung as well as its immunology is helpful in understanding the radiologic and pathologic findings of the primary pulmonary lymphoid lesions. Primary lymphoid lesions of the lung arise from the BALT and are uncommon. However, they are increasingly recognized within the growing number of posttransplant patients as well as other patients who are receiving immunosuppressive therapies. Primary lymphoid lesions encompass a wide range of benign and malignant lesions. Benign lymphoid lesions of the lung include reactive lymphoid hyperplasia, follicular bronchiolitis, lymphoid interstitial pneumonia, and nodular lymphoid hyperplasia. Malignant lymphoid lesions of the lung include low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), other non-Hodgkin lymphomas, and Hodgkin lymphoma. Last, a miscellaneous group of primary lymphoid lesions includes lymphomatoid granulomatosis, posttransplant lymphoproliferative disorders, acquired immunodeficiency syndrome (AIDS)-related lymphoma, and intravascular lymphoma/lymphomatosis. These lesions are best evaluated with multidetector chest computed tomography. The radiologic findings of the primary lymphoid lesions are often nonspecific and are best interpreted in correlation with clinical data and pathologic findings. The purpose of this article is to review pulmonary lymphoid anatomy as well as the most common primary pulmonary lymphoid disorders. (©)RSNA, 2016.

PMID: 26761531 [PubMed – as supplied by publisher]

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Related Articles

Primary sclerosing cholangitis in common variable immune deficiency.

Allergol Int. 2015 Apr;64(2):187-9

Authors: Mahdavinia M, Mirsaeidi M, Bishehsari F, McGrath K

PMID: 25838096 [PubMed – indexed for MEDLINE]

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Helicobacter pylori infection in patients with selective immunoglobulin A deficiency.

Clin Exp Immunol. 2016 Jan 8;

Authors: Magen E, Waitman DA, Goldstein N, Schlesinger M, Dickstein Y, Kahan NR

Abstract
BACKGROUND: Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in the Western world. The aim of the study was to investigate the prevalence and clinical characteristics of Helicobacter pylori (H. pylori) infected dyspeptic patients with IgAD.
MATERIALS AND METHODS: Case samples were drawn from all subjects ≥ 12 years of age (n = 104729), who that had undergone serum total IgA measurements during 2004 – 2014 years for any reason at Leumit Healthcare Services (Israel) and had serum total IgA <0.07 g/L. The control group was comprised of a random sample of remaining patients with a case-control ratio ten controls for each case. The dyspeptic diseases were identified and retrieved from Leumit Health Care Services electronic database using specific ICD-9-CM diagnostic codes.
RESULTS: Case group included 347 subjects and Control group 3470 subjects. There were no significant difference in the prevalence of patients with dyspepsia (84 (24.2%) vs 821 (23.6%) for cases and controls, respectively). Additionally, there was no difference in a proportion of dyspeptic H. pylori-positive subjects (59 (17.1%) vs 524 (15.1%) between the case and control groups.Only 59 (17%) among the 347 IgAD patients underwent gastroscopy. Crude numbers of all the patients with experienced gastritis. A significantly larger proportion of case subjects experienced several forms gastritis (13 (61.9%) vs.38 (21.6%), p<0.001), duodenal ulcers (7 (33.3%) vs 19 (10.8%); p = 0.01) and nodular lymphoid hyperplasia (NLH) (2 (9.5%) vs 0; p=0.011).
CONCLUSIONS: IgAD is not associated with increased prevalence of H. pylori associated dyspepsia, nevertheless H.pylori infected dyspeptic IgAD subjects experience more EGD proved gastritis, duodenal ulcers and NLH. This article is protected by copyright. All rights reserved.

PMID: 26749258 [PubMed – as supplied by publisher]

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Clinical and structural impact of mutations affecting the residue Phe367 of FOXP3 in patients with IPEX syndrome.

Clin Immunol. 2015 Dec 31;

Authors: Colobran R, de la Campa EÁ, Soler-Palacín P, Martín-Nalda A, Pujol-Borrell R, de la Cruz X, Martínez-Gallo M

Abstract
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic autoimmune disease characterized by early-onset life-threatening multisystemic autoimmunity. This rare hereditary disorder is caused by loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor, which plays a key role in the differentiation and function of CD4(+)CD25(+) natural regulatory T cells (Tregs), essential for the establishment and maintenance of natural tolerance. We identified a novel mutation in the FOXP3 gene affecting the Phe367 residue of the protein (F367V) in a family with three male siblings affected by IPEX. Two other mutations affecting the FOXP3 Phe367 residue (F367L and F367C) have been described previously. This unique situation of three mutations affecting the same residue in FOXP3 led us to study the molecular impact of these mutations on the structure of FOXP3 protein. Structure analysis showed that Phe367 is involved in a rich interaction network related to both monomer and dimer structure stabilization, and is crucial for FOXP3 regulatory activity. The relevance of this location is confirmed by the results of SIFT and PolyPhen-2 pathogenicity predictions for F367V mutation. In summary, as assessment of the pathogenicity of a novel mutation is crucial to achieve a proper molecular diagnosis, we analysed the impact of mutations affecting the Phe367 residue using a combined approach that provides a mechanistic view of their pathogenic effect.

PMID: 26748374 [PubMed – as supplied by publisher]

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Common variable immunodeficiency diagnosed during the treatment of bronchial asthma: Unusual cause of wheezing.

Respir Med Case Rep. 2015;16:41-4

Authors: Akaba T, Kondo M, Toriyama M, Kubo A, Hara K, Yamada T, Yoshinaga K, Tamaoki J

Abstract
Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency in adults and children. We herein report a case of CVID, who was misdiagnosed with asthma due to wheezing episodes and relatively late onset. A 51-year-old woman had suffered from recurrent upper and lower airway infection for recent 2 years. She repeated wheezing attacks and was treated as asthma exacerbation triggered by infection. She was referred to our hospital for investigation and treatment. Lung function tests showed no reversibility of FEV1 by β-adrenergic agonist, but the increase of V50/V25. Chest CT showed slight to moderate bronchial wall thickening and bronchiectasis. After that, she suffered from pneumonia with wheezing attacks twice a month, and immunodeficiency was strongly suspected. Her blood tests showed marked decreases of all classes of immunoglobulin and nearly lack of memory B cells, NKT cells and plasmacytoid dendritic cells. She was diagnosed with CVID, and was treated with replacement of gammaglobulin. Thereafter, her wheezing episodes with infection were remarkably improved. Because the delay of diagnosis with CVID likely causes poor mortality and morbidity, a possibility of CVID should be considered in patients with frequent asthma-like symptoms due to recurrent airway infection.

PMID: 26744651 [PubMed]

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Advances in Understanding the Pathogenesis of Epstein-Barr Virus-Associated Lymphoproliferative Disorders.

Iran J Allergy Asthma Immunol. 2015 Oct;14(5):462-71

Authors: Yang X, Nishida N, Zhao X, Kanegane H

Abstract
Epstein-Barr virus (EBV) was discovered 50 years ago  from an african Burkitt lymphoma cell line. EBV-associated lymphoproliferative disorders (LPDs) are life- threatening diseases, especially in children. In this article, we review EBV-associated LPDs, especially in the area of primary immunodeficiency disease (PID). We searched PubMed for publications with key words including EBV infection, lymphoma, LPDs and PID, and selected the manuscripts written in English that we judged to be relevant to the topic of this review.On the basis of the data in the literature, we grouped the EBV-associated LPDs into four categories: nonmalignant disease, malignant disease, acquired immunodeficiency disease and PID. Each category has its own risk factor for LPD development. EBV-associated LPD is a complex disease, creating new challenges for diagnosis and treatment.

PMID: 26742434 [PubMed – in process]

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A case of APDS patient: defects in maturation and function and decreased in vitro anti-mycobacterial activity in the myeloid compartment.

Clin Immunol. 2015 Dec 27;

Authors: Chiriaco M, Brigida I, Ariganello P, Di Cesare S, Di Matteo G, Taus F, Cittaro D, Lazarevic D, Scarselli A, Santilli V, Attardi E, Stupka E, Giannelli S, Fraziano M, Finocchi A, Rossi P, Aiuti A, Palma P, Cancrini C

Abstract
Activated PI3-Kinase Delta Syndrome (APDS) was recently reported as a novel Primary Immunodeficiency caused by heterozygous gain-of-function mutations in PIK3CD gene. Here we describe immunological studies in a 19 years old APDS patient for whom genetic diagnosis was discovered by Whole Exome Sequencing (WES) analysis. In addition to the progressive lymphopenia and defective antibody production we showed that the ability of patient’s B cells to differentiate in vitro is severely reduced. An in depth analysis of the myeloid compartment showed an increased expression of CD83 activation marker on monocytes and mono-derived DC cells. Moreover, monocytes-derived macrophages (MDM) failed to solve Mycobacterium bovis bacillus Calmette Guèrin (BCG) infection in vitro. Selective p110δ inhibitor IC87114 restored the MDM capacity to kill BCG in vitro. Our data show that the constitutive activation of Akt-mTOR pathway induces important alterations also in the myeloid compartment providing new insights in order to improve therapeutic approach in these patients.

PMID: 26732860 [PubMed – as supplied by publisher]

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Parental Views on Expanded Newborn Screening Using Whole-Genome Sequencing.

Pediatrics. 2016 Jan;137 Suppl 1:S36-46

Authors: Joseph G, Chen F, Harris-Wai J, Puck JM, Young C, Koenig BA

Abstract
BACKGROUND AND OBJECTIVE: The potential application of whole-genome sequencing (WGS) to state-mandated standard newborn screening (NBS) challenges the traditional public health approach to NBS and raises ethical, policy, and clinical practice issues. This article examines the perspectives and values of diverse healthy pregnant women and parents of children diagnosed with a primary immunodeficiency disorder about traditional NBS and expanded NBS with the use of WGS.
METHODS: We conducted 4 focus groups (3 in English and 1 in Spanish) with socioeconomically and ethnically diverse pregnant women (n = 26), and a comparison group with parents of children diagnosed with a primary immunodeficiency disorder (n = 5).
RESULTS: Pediatric policy-relevant themes that emerged from our analysis of the focus group data are presented within 4 categories: (1) perspectives on traditional NBS, (2) informed consent, (3) return of results, and (4) storage and retrieval of results. Analyses indicate that study participants desired greater inclusion in the NBS process. Despite an optimistic orientation to the potential benefits and limited harms likely to result from genomic applications of NBS, parents voiced concerns about privacy and control over test results. Limited trust in the medical system and the state-run NBS program informed these concerns.
CONCLUSIONS: Expanded NBS with WGS for pediatricians may require management of more genetic conditions, including mutations that convey risk to both the child and parents for adult-onset disorders, and an informed-consent process to manage the genomic data and storage of blood spots. Attention to how these technologies are understood in diverse populations is needed for effective implementation.

PMID: 26729702 [PubMed – in process]

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Noninfectious Granulomas: A Sign of an Underlying Immunodeficiency?

J Cutan Med Surg. 2016 Jan 4;

Authors: Shoimer I, Wright N, Haber RM

Abstract
Primary immunodeficiency disorders, such as ataxia-telangiectasia (A-T), may rarely be associated with cutaneous granulomas without an identifiable infection. The authors report a case of a 3-year-old boy with A-T who presented with two persistent ulcerated erythematous nodules. Histopathology was consistent with a granulomatous process secondary to A-T, without an infectious origin. Partial improvement was noted with clobetasol propionate 0.05% cream applied twice daily under occlusion. Of note, the presence of multiple noninfectious granulomas in a child may be the initial sign of an immune deficiency and should alert the astute clinician to investigate for an underlying primary immunodeficiency. Herein, the authors discuss the associations of noninfectious granulomas and primary immunodeficiency disorders and present management options for these difficult-to-treat lesions.

PMID: 26728658 [PubMed – as supplied by publisher]

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