Research

Successful oral treatment of Ganciclovir resistant cytomegalovirus with Maribavir in the context of primary immunodeficiency: First case report and review.

J Clin Virol. 2016 Dec 12;87:12-16

Authors: Bright PD, Gompels M, Donati M, Johnston S

PMID: 27987421 [PubMed – as supplied by publisher]

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Comprehensive genetic testing for primary immunodeficiency disorders in a tertiary hospital: 10-year experience in Auckland, New Zealand.

Allergy Asthma Clin Immunol. 2016;12:65

Authors: Woon ST, Ameratunga R

Abstract
BACKGROUND AND PURPOSE: New Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million. Genetic diagnosis is the standard of care for most patients with primary immunodeficiency disorders (PIDs).
METHODS: Since 2005, we have offered a comprehensive genetic testing service for PIDs and other immune-related disorders with a published sequence. Here we present results for this program, over the first decade, between 2005 and 2014.
RESULTS: We undertook testing in 228 index cases and 32 carriers during this time. The three most common test requests were for X-linked lymphoproliferative (XLP), tumour necrosis factor receptor associated periodic syndrome (TRAPS) and haemophagocytic lymphohistiocytosis (HLH). Of the 32 suspected XLP cases, positive diagnoses were established in only 2 patients. In contrast, genetic defects in 8 of 11 patients with suspected X-linked agammaglobulinemia (XLA) were confirmed. Most XLA patients were initially identified from absence of B cells. Overall, positive diagnoses were made in about 23% of all tests requested. The diagnostic rate was lowest for several conditions with locus heterogeneity.
CONCLUSIONS: Thorough clinical characterisation of patients can assist in prioritising which genes should be tested. The clinician-driven customised comprehensive genetic service has worked effectively for New Zealand. Next generation sequencing will play an increasing role in disorders with locus heterogeneity.

PMID: 27980540 [PubMed – in process]

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Gene mutations responsible for primary immunodeficiency disorders: A report from the first primary immunodeficiency biobank in Iran.

Allergy Asthma Clin Immunol. 2016;12:62

Authors: Sheikhbahaei S, Sherkat R, Roos D, Yaran M, Najafi S, Emami A

Abstract
BACKGROUND: Primary immunodeficiency (PID) is a heterogeneous group of inheritable genetic disorders with increased susceptibility to infections, autoimmunity, uncontrolled inflammation and malignancy. Timely precise diagnosis of these patients is very essential since they may not be able to live with their congenital immunity defects; otherwise, they could survive with appropriate treatment. DNA biobanks of such patients could be used for molecular and genetic testing, facilitating the detection of underlying mutations in known genes as well as the discovery of novel genes and pathways.
METHODS: According to the last update of the International Union of Immunological Societies (IUIS) classification, patients are registered in our biobank during a period of 15 years. All patients’ data were collected via questionnaire and their blood samples were taken in order to extract and protect their DNA content.
RESULTS: Our study comprised 197 patients diagnosed with PID. Antibody deficiency in 50 patients (25.4%), phagocytic defect in 47 patients (23.8%) and combined immunodeficiency with associated/syndromic feature in 19 patients (9.6%) were the most common PID diagnoses, respectively. The most common variant of PID in our study is common variable immunodeficiency, which accounted for 20 cases (10.1%), followed by chronic mucocutaneous candidiasis in 15 patients (7.9%) and congenital neutropenia in 13 patients (7%). Mean age at onset of disease was 4 years and mean age of diagnosis was 9.6 years. The average diagnostic delay was 5.5 years, with a range of 6 months to 46 years. Parental consanguinity and history of PID in family were observed in 70.2 and 48.9% of the patients, respectively. The majority of PID patients (93.3%) were from families with low socioeconomic status.
CONCLUSION: This prospective study was designed to establish a PID Biobank in order to have a high quality DNA reservoir of these patients, shareable for international diagnostic and therapeutic collaborations. This article emphasizes the need to raise the awareness of society and general practitioners to achieve timely diagnosis of these patients and prevent current mismanagements.

PMID: 27980538 [PubMed – in process]

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Nodular lymphoid hyperplasia complicated with ileal Burkitt’s lymphoma in an adult patient with selective IgA deficiency.

Int J Surg Case Rep. 2016 Nov 22;30:69-72

Authors: Hanich T, Majnarić L, Janković D, Šabanović Š, Včev A

Abstract
INTRODUCTION: Primary lymphomas of the small intestine are rare. Burkitt’s lymphoma (BL) occurs sporadically in adults. Nodular lymphoid hyperplasia (NLH) is a rare disorder characterized by diffuse nodular lesions, which represent hyperplastic lymphoid follicles, and it is often associated with immunodeficiency syndromes.
PRESENTATION OF CASE: We present a 38-year-old male patient in a state of surgical emergency, suspected of Crohn’s disease, who had an unusual combination of NLH and BL of the proximal ileum. Furthermore, retrospectively analyzed documentation revealed selective IgA deficiency.
DISCUSSION: Association between NLH and intestinal lymphomas in patients with immunodeficiency syndromes was indicated before. This case report supports the notion on NLH as a transition state between immunodeficiency and intestinal lymphomas.
CONCLUSION: This is one of the first case reports which presents the combination of NHL and BL. The awareness of the existence of this rare combination, especially in young adult males, can improve the diagnostic accuracy and the treatment management.

PMID: 27940199 [PubMed – as supplied by publisher]

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CD34 Antigen and the MPL Receptor Expression Defines A Novel Class Of Human Cord Blood-derived Primitive Hematopoietic Stem Cells.

Cell Transplant. 2016 Nov 30;:

Authors: Matsuoka Y, Takahashi M, Sumide K, Kawamura H, Nakatsuka R, Fujioka T, Sonoda Y

Abstract
In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34-negative (CD34<sup>-</sup>) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CBderived 18Lin<sup>-</sup>CD34<sup>+/-</sup>MPL<sup>+/-</sup> cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34<sup>+/-</sup>MPL<sup>+/-</sup> cells were repopulated with human CD45<sup>+</sup> cells. Nearly all of these mice that received CD34<sup>+</sup>MPL<sup>+/-</sup> and CD34<sup>-</sup> MPLcells showed a secondary repopulation. Interestingly, both the secondary recipient mice that received CD34<sup>+/-</sup>MPL<sup>-</sup>cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34<sup>+/-</sup> SRCs not expressing MPL sustain a long-term (LT) (> 1 year) human cell repopulation in NOG mice. Moreover, CD34<sup>-</sup> SRCs generate CD34<sup>+</sup>CD38<sup>-</sup>CD90<sup>+</sup> SRCs <em>in vitro</em> and <em>in vivo</em>. These findings provide a new concept that CD34<sup>-</sup>MPL<sup>-</sup> SRCs reside at the apex of the human HSC hierarchy.

PMID: 27938494 [PubMed – as supplied by publisher]

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Primary immunodeficiencies associated with EBV-Induced lymphoproliferative disorders.

Crit Rev Oncol Hematol. 2016 Dec;108:109-127

Authors: Shabani M, Nichols KE, Rezaei N

Abstract
Primary immunodeficiency diseases (PIDs) are a subgroup of inherited immunological disorders that increase susceptibility to viral infections. Among the range of viral pathogens involved, EBV remains a major threat because of its high prevalence of infection among the adult population and its tendency to progress to life-threatening lymphoproliferative disorders (LPDs) and/or malignancy. The high mortality in immunodeficient patients with EBV-driven LPDs, despite institution of diverse and often intensive treatments, prompts the need to better study these PIDs to identify and understand the affected molecular pathways that increase susceptibility to EBV infection and progression. In this article, we have provided a detailed literature review of the reported cases of EBV-driven LPDs in patients with PID. We discuss the PIDs associated with development of EBV-LPDs. Then, we review the nature and the therapeutic outcome of common EBV- driven LPDs in the PID patients and review the mechanisms common to the major PIDs. Deep study of these common pathways and gaining a better insight into the disease nature and outcomes, may lead to earlier diagnosis of the disease, choosing the best treatment modalities available and development of novel therapeutic strategies to decrease morbidity and mortality brought about by EBV infection.

PMID: 27931829 [PubMed – in process]

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Liver transplantation in patients with primary antibody deficiency.

J Allergy Clin Immunol. 2016 Dec 05;:

Authors: Jørgensen SF, Macpherson ME, Bjøro K, Karlsen TH, Reims HM, Grzyb K, Fosby B, Fevang B, Aukrust P, Nordøy I

Abstract
Patients with primary antibody deficiency and liver failure should be considered for liver transplantation and not rejected because of their immunodeficiency alone. Improved anti-fungal prophylaxis may further improve their prognosis.

PMID: 27931972 [PubMed – as supplied by publisher]

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Pulmonologist perspectives regarding diagnosis and management of primary immunodeficiency diseases.

Allergy Asthma Proc. 2016 Nov;37(6):162-168

Authors: Orange JS, Akhter J, Seeborg FO, Boyle M, Scalchunes C, Hernandez-Trujillo V

Abstract
BACKGROUND: The time from symptom onset to diagnosis for patients with primary immunodeficiency diseases (PIDD) is an average of 12 years, but prompt diagnosis and treatment can promote best outcomes.
OBJECTIVE: Because the manifestations of PIDD are often sinopulmonary in nature, patients with undiagnosed PIDD are frequently referred to pulmonologists. This study sought to identify opportunities among these specialists to improve diagnosis and clinical management of patients with PIDD.
METHODS: A survey was sent to American Medical Association and American Osteopathic Association members whose specialty was pulmonology. Responses were compared with those from a historical survey of 71 subspecialist immunologists (American Academy of Allergy, Asthma Immunology members who devoted 10% of their practice to patients with PIDD).
RESULTS: The surveys were returned by 485 pulmonologists, 49% of whom had diagnosed at least one patient with PIDD. In comparison with subspecialist immunologists, fewer pulmonologists were aware of the professional PIDD diagnosis and management guidelines and fewer followed up patients with various PIDDs. Pulmonologists and subspecialist immunologists also differed in the practice of prescribing prophylactic antibiotics and immunoglobulin replacement and in avoiding live viral vaccines.
CONCLUSION: Differences in the diagnosis and treatment of patients with PIDD between these two groups of specialists revealed areas in which PIDD-focused educational initiatives may be helpful for pulmonologists.

PMID: 27931293 [PubMed – in process]

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