Research

Primary Immunodeficiency Masquerading as Allergic Disease.

Immunol Allergy Clin North Am. 2015 Nov;35(4):767-778

Authors: Chan SK, Gelfand EW

Abstract
Primary immune deficiencies (PIDs) are an uncommon heterogeneous group of diseases that result from fundamental defects in the proteins and cells that enable specific immune responses. Common allergic reactions (eczema, allergic rhinitis, asthma, and food allergies) are exaggerated immune responses that may be manifestations of an underlying PID. Early diagnosis and treatment has significant bearing on outcome. Immune suppression with systemic corticosteroids in these immune compromised individuals can lead to life threatening dissemination of infections.

PMID: 26454318 [PubMed – as supplied by publisher]

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Primary Immunodeficiency Disorders.

Immunol Allergy Clin North Am. 2015 Nov;35(4):ix-x

Authors: Montanaro A

PMID: 26454319 [PubMed – as supplied by publisher]

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Autoimmune Disease in Primary Immunodeficiency: At the Crossroads of Anti-Infective Immunity and Self-Tolerance.

Immunol Allergy Clin North Am. 2015 Nov;35(4):731-752

Authors: Saifi M, Wysocki CA

Abstract
The association of autoimmunity and primary immunodeficiency suggests the existence of mechanistic links between development of the various elements of the immune system and the maintenance of self-tolerance. In this review, various monogenic primary immunodeficiencies (PID) are systematically explored, with a specific focus on the impact of these genetic lesions on tolerance, correlating these defects in tolerance with clinical autoimmune and inflammatory syndromes seen in these PIDs. Common variable immunodeficiency (CVID) is explored, and areas are highlighted in which findings in monogenic PID are beginning to illuminate the mechanisms behind these conditions in CVID.

PMID: 26454316 [PubMed – as supplied by publisher]

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Pulmonary Manifestations of Primary Immunodeficiency Disorders.

Immunol Allergy Clin North Am. 2015 Nov;35(4):753-766

Authors: Nonas S

Abstract
Pulmonary disease, ranging from infectious pneumonia, lung abscess, and empyema to structural lung diseases to malignancy, significantly increase morbidity and mortality in primary immune deficiency. Treatment with supplemental immunoglobulin (intravenous or subcutaneous) and antimicrobials is beneficial in reducing infections but are largely ineffective in preventing noninfectious complications, including interstitial lung disease, malignancy, and autoimmune disease. A low threshold for suspecting pulmonary complications is necessary for the early diagnosis of pulmonary involvement in primary immunodeficiency disorders, before irreversible damage is done, to improve patient outcomes.

PMID: 26454317 [PubMed – as supplied by publisher]

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Hematopoietic Stem Cell Transplant for Immune Deficiency and Immune Dysregulation Disorders.

Immunol Allergy Clin North Am. 2015 Nov;35(4):695-711

Authors: Hagin D, Burroughs L, Torgerson TR

Abstract
Primary immunodeficiency disorders were among the first diseases in which hematopoietic stem cell transplant (HSCT) was attempted. Initial attempts at HSCT were discouraging and fraught with complications, but with increased knowledge and sophistication of HLA typing and donor matching, development of improved transplant conditioning regimens, and advances in prophylaxis and treatment of graft-versus-host disease, there has been a marked improvement in outcomes. This improvement has allowed an ever-growing number of different immunodeficiency and immune dysregulation disorders to be treated by HSCT. This article provides an overview of the approach to HSCT in these disorders.

PMID: 26454314 [PubMed – as supplied by publisher]

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Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

Immunol Allergy Clin North Am. 2015 Nov;35(4):713-730

Authors: Sriaroon P, Ballow M

Abstract
Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.

PMID: 26454315 [PubMed – as supplied by publisher]

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Overview of Immunodeficiency Disorders.

Immunol Allergy Clin North Am. 2015 Nov;35(4):599-623

Authors: Raje N, Dinakar C

Abstract
The spectrum of primary immunodeficiency disorders (PIDs) is expanding. It includes typical disorders that primarily present with defective immunity as well as disorders that predominantly involve other systems and show few features of impaired immunity. The rapidly growing list of new immunodeficiency disorders and treatment modalities makes it imperative for providers to stay abreast of the latest and best management strategies. This article presents a brief overview of recent clinical advances in PIDs.

PMID: 26454309 [PubMed – as supplied by publisher]

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Common Variable Immunodeficiency: Diagnosis, Management, and Treatment.

Immunol Allergy Clin North Am. 2015 Nov;35(4):637-658

Authors: Abbott JK, Gelfand EW

Abstract
Common variable immunodeficiency (CVID) refers to a grouping of antibody deficiencies that lack a more specific genetic or phenotypic classification. It is the immunodeficiency classification with the greatest number of constituents, likely because of the numerous ways in which antibody production can be impaired and the frequency in which antibody production becomes impaired in human beings. CVID comprises a heterogeneous group of rare diseases. Consequently, CVID presents a significant challenge for researchers and clinicians. Despite these difficulties, both our understanding of and ability to manage this grouping of complex immune diseases has advanced significantly over the past 60 years.

PMID: 26454311 [PubMed – as supplied by publisher]

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Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome.

J Clin Immunol. 2015 Oct 9;

Authors: Mócsai G, Gáspár K, Dajnoki Z, Tóth B, Gyimesi E, Bíró T, Maródi L, Szegedi A

Abstract
PURPOSE: Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients.
METHODS: In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n = 7) and AD (n = 49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined.
RESULTS: Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES.
CONCLUSIONS: Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. A well-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization.

PMID: 26453584 [PubMed – as supplied by publisher]

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Interleukin-17A promotes the growth of human germinal center derived non-Hodgkin B cell lymphoma.

Oncoimmunology. 2015 Oct;4(10):e1030560

Authors: Ferretti E, Di Carlo E, Ognio E, Guarnotta C, Bertoni F, Corcione A, Prigione I, Fraternali-Orcioni G, Ribatti D, Ravetti JL, Ponzoni M, Tripodo C, Pistoia V

Abstract
Interleukin (IL)-17A belongs to IL-17 superfamily and binds the heterodimeric IL-17 receptor (R)(IL-17RA/IL-17RC). IL-17A promotes germinal center (GC) formation in mouse models of autoimmune or infectious diseases, but the role of IL-17A/IL-17AR complex in human neoplastic GC is unknown. In this study, we investigated expression and function of IL-17A/IL-17AR in the microenvironments of 44 B cell non-Hodgkin lymphomas (B-NHL) of GC origin (15 follicular lymphomas, 17 diffuse large B cells lymphomas and 12 Burkitt lymphomas) and 12 human tonsil GC. Furthermore, we investigated the role of IL-17A in two in vivo models of GC B cell lymphoma, generated by s.c. injection of SU-DHL-4 and OCI-Ly8 cell lines in Severe combined immunodeficiency (SCID)/Non Obese Diabetic (NOD) mice. We found that: (i) B-NHL cell fractions and tonsil GC B cells expressed IL-17RA/IL-17RC, (ii) IL-17A signaled in both cell types through NF-kBp65, but not p38, ERK-1/2, Akt or NF-kBp50/105, phosphorylation, (iii) IL-17A was expressed in T cells and mast cells from neoplastic and normal GC microenvironments, (iv) IL-17A rendered tonsil GC B cells competent to migrate to CXCL12 and CXCL13 by downregulating RGS16 expression; (v) IL-17A stimulated in vitro proliferation of primary B-NHL cells; (vi) IL-17A (1 μg/mouse-per dose) stimulated B-NHL growth in two in vivo models by enhancing tumor cell proliferation and neo-angiogenesis. This latter effect depended on IL-17A-mediated induction of pro-angiogenic gene expression in tumor cells and direct stimulation of endothelial cells. These data define a previously unrecognized role of human IL-17A in promoting growth of GC-derived B-NHL and modulating normal GC B cell trafficking.

PMID: 26451300 [PubMed – as supplied by publisher]

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