Research

The immunophenotypical fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives.

Haematologica. 2016 Sep 15;

Authors: Bogaert DJ, De Bruyne M, Debacker V, Depuydt P, De Preter K, Bonroy C, Philippe’ J, Bordon V, Lambrecht BN, Kerre T, Cerutti A, Vermaelen KY, Haerynck F, Dullaers M

Abstract
The etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in-depth, only few reports exist on milder primary antibody deficiencies like idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 common variable immunodeficiency, 23 idiopathic primary hypogammaglobulinemia and 21 IgG subclass deficiency patients, and in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls. All three patient groups showed decreased memory B and naive T cell subsets and decreased B-cell activating factor receptor expression. In contrast, circulating follicular helper T cell frequency and expression of inducible T-cell co-stimulator and chemokine receptors were significantly altered in common variable immunodeficiency patients only. Asymptomatic first-degree family members of patients demonstrated similar, albeit intermediate, alterations in naive and memory B and T cell subsets. About 13% of asymptomatic relatives had an abnormal peripheral B cell composition. Furthermore, asymptomatic relatives showed decreased CD4+ recent thymic emigrants and increased central memory T cells. Serum IgG and IgM levels were also significantly lower in asymptomatic relatives compared to healthy controls. We conclude that, in our cohort, the immunophenotypical landscape in primary antibody deficiencies comprises a spectrum, in which some alterations are shared between all primary antibody deficiencies whereas others are only associated with common variable immunodeficiency. Importantly, asymptomatic first-degree family members of patients are found to have an intermediate phenotype for peripheral B and T cell subsets.

PMID: 27634199 [PubMed – as supplied by publisher]

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Chronic Giardiasis in a Case of Common Variable Immunodeficiency (CVID): A Case Report.

J Clin Diagn Res. 2016 Jul;10(7):DD03-DD04

Authors: Paranjpe SM, Koticha A, Mehta PR

Abstract
Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by low antibody levels and recurrent infections. This makes an individual more prone to recurrent respiratory and gastrointestinal tract infections. In cases where there is persistent positive finding of intestinal parasites in stool, a high index of suspicion should be raised to rule out immunodeficiency state. Early diagnosis of such cases will help in reducing the morbidity and better management of the patient. A case of CVID in 18-year-old male with recurrent lower respiratory tract infection and chronic diarrhoea due to Giardia lamblia is reported herewith.

PMID: 27630845 [PubMed – as supplied by publisher]

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A case report of primary orbital non-Hodgkin’s lymphoma causing complete vision loss.

GMS Ophthalmol Cases. 2016;6:Doc06

Authors: Lamba N, Dworak DP, Patel SA, Chennuri R

Abstract
A 29-year-old male with acquired immunodeficiency syndrome presented with a week of left eye blurriness, which then progressed to complete vision loss. On exam, the left pupil was nonreactive to light, and fundoscopy showed significant optic nerve edema. CT and MRI of the left orbit showed a mass lesion compressing the posterior aspect of the sclera with diffuse thickening and contrast enhancement of the retrobulbar portion of the left optic nerve. The lesion demonstrated low T1 and intermediate T2 intensities and heterogeneous contrast enhancement and measured 17.4 mm x 15 mm x 10.6 mm. Anterior orbitotomy with exploration and biopsy were performed. Immunohistochemical studies confirmed diffuse large B-cell lymphoma and a workup showed no systemic involvement. Plans for treatment with chemotherapy and radiation were initiated. Even though rare, primary orbital NHL should be in the differential for relatively acute blindness without other symptoms, especially in patients with AIDS.

PMID: 27625965 [PubMed]

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Successful immune reconstitution by means of hematopoietic stem cell transplantation in a Colombian patient with chronic granulomatous disease.

Biomedica. 2016;36(2):204-212

Authors: Rocha YC, López JÁ, Orrego JC, Coll Y, Karduss A, Rosenzweig S, Franco JL

Abstract
INTRODUCTION: Chronic granulomatous disease is a primary immunodeficiency that results from mutations in proteins of the NADPH oxidase system that affect the microbicidal activity of phagocytes. Immune reconstitution by hematopoietic stem cell transplantation is currently the only curative therapy for this disease. Objective: To describe the clinical and molecular characterization of a patient with X-linked chronic granulomatous disease and the successful immune reconstitution by means of a hematopoietic stem cell transplantation. Methods: The respiratory burst was measured by flow cytometry using the dihydrorodamine 123 (DHR) oxidation test in neutrophils of peripheral blood. Mutational analysis of CYBB was performed by PCR amplification in complementary DNA, as well as sequencing and comparative genomic hybridization in genomic DNA. HLA-identical stem cells from the patient’s younger brother were used for the transplantation and reduced intensity pre-transplantation conditioning was administered. Post-transplantation immune reconstitution was evaluated periodically by serial complete blood counts and DHR 123 in peripheral blood neutrophils. Results: The diagnosis of X-linked chronic granulomatous disease resulted from a hemizygous deletion affecting Xp21.1 that included the entire CYBB. Post-transplantation engraftment was documented in platelets and peripheral blood neutrophils at days 10 and 11, respectively. Total hematological reconstitution was achieved by day 30 post-transplantation and no complications or infections have been observed in the three years since the transplantation. Conclusion: Hemopoietic stem cell transplantation allows for total reconstitution of the immune function related to microbicidal activity of phagocytic cells from patients with X-linked chronic granulomatous disease.

PMID: 27622481 [PubMed – as supplied by publisher]

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PI3Kδ and primary immunodeficiencies.

Nat Rev Immunol. 2016 Sep 12;

Authors: Lucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K

Abstract
Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy.

PMID: 27616589 [PubMed – as supplied by publisher]

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[Case Report; Primary central nervous system lymphoma mimicking progressive multifocal leukoencephalopathy in a patient with acquired immune deficiency syndrome].

Nihon Naika Gakkai Zasshi. 2014 Oct 10;103(10):2578-80

Authors: Yamakawa T, Fujimoto K, Ebata K, Iwasaki J, Takahashi S, Shiratori S, Sugita J, Kondo T, Nishio M, Teshima T

PMID: 27514208 [PubMed – indexed for MEDLINE]

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[Specific antibody deficiency: Primary immunodeficiency associated to respiratory allergy].

Rev Chil Pediatr. 2016 Sep 7;

Authors: Fernández F, Campillay R, Palma V, Norambuena X, Quezada A

Abstract
INTRODUCTION: Specific antibody deficiency (SAD) with normal immunoglobulin and normal B cells is a primary immunodeficiency characterized by reduced ability to produce antibodies to specific antigens especially polysaccharides.
OBJECTIVE: To describe the characteristics of patients diagnosed with SAD emphasizing the association between primary immunodeficiency and allergic diseases.
PATIENTS AND METHOD: Descriptive study showing patients with SAD treated at a public hospital between August 2007 and July 2015. Other secondary or primary immunodeficiency was discarded. The diagnosis of SAD was based on recurrent infections and abnormal response to pneumococcal polysaccharide vaccine assessed by specific IgG to 10 pneumococcal serotypes.
RESULTS: Twelve patients were included, 4 males, mean age 6 years, recurrent pneumonia predominated (91.7%) as well as other respiratory and invasive infections. All patients with SAD had associated asthma, 11 had allergic rhinitis, and other allergies. Three patients did not respond to any of the 10 serotypes contained in pneumococcal polysaccharide vaccine, and those who responded were with low titers. Treatment with conjugate pneumococcal vaccine was favorable in 11/12 patients.
CONCLUSION: In children older than 2 years with recurrent respiratory infections or invasive S. pneumoniae infections with normal immunoglobulin we recommend to investigate SAD, especially if they have a concurrent allergic disease.

PMID: 27614984 [PubMed – as supplied by publisher]

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Cellular and molecular mechanisms of immune dysregulation and autoimmunity.

Cell Immunol. 2016 Aug 27;

Authors: Azizi G, Pouyani MR, Abolhassani H, Sharifi L, Dizaji MZ, Mohammadi J, Mirshafiey A, Aghamohammadi A

Abstract
Primary immunodeficiencies (PIDs) constitute a large group of rare disorders that affect the function of the immune system. A specific group of PIDs entitled “diseases of immune dysregulation” are developed due to mutation in the genes which have critical roles in the regulation of immune responses and immunological tolerance. This group of PID patients develop autoimmune and inflammatory disorders as a result of their impaired immunity, therefore they could be considered as a model for analyzing the link between immune dysregulation and autoimmunity. In this article, our aim is to describe the function of the mutated gene, the molecular and cellular mechanisms underlying the immune dysregulation and review the literature in regard with the reported autoimmune disorders in the main types of immunodysregulatory diseases including genetic defects of regulatory T cells, familial hemophagocytic lymphohistiocytosis syndromes, autoimmunity without lymphoproliferation, autoimmune lymphoproliferative syndrome, immune dysregulation with colitis, and type 1 interferonopathies.

PMID: 27614846 [PubMed – as supplied by publisher]

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Ataxia telangiectasia presenting as hyper IgM syndrome without neurologic signs.

Ann Allergy Asthma Immunol. 2016 Sep;117(3):221-6

Authors: Doshi A, Ryu J, Thornburg CD, Hershey D, Cherry R, Milligan K, Rosenzweig S, Leonard S

PMID: 27613453 [PubMed – in process]

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Chronic granulomatous disease as an SOS call for multicenter cooperative effort to prevent infections: A meta-analysis of the treatments.

Ann Allergy Asthma Immunol. 2016 Sep;117(3):285-9

Authors: Loffredo L, Perri L, Zicari A, Del Ben M, Angelico F, Violi F

Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease. Patients with CGD experience recurrent life-threatening infections. Lack of large interventional trials generated several doubts for the treatment of infections in CGD.
OBJECTIVE: To evaluate the effect of interferon gamma, antifungal drugs, and antibiotics in patients with CGD undergoing prophylaxis of infections.
METHODS: A meta-analysis of the interventional trials was performed. The studies were identified by searching MEDLINE, ISI Web of Science, SCOPUS, and Cochrane database. The last search was run on January 2016. Reference lists of all studies included in the present systematic review were screened for potential additional eligible studies.
RESULTS: Two studies with 163 patients with CGD were included in the interferon gamma analysis. Severe infections occurred in 17 of 73 patients (23%) treated with interferon gamma and in 49 of 90 patients (54%) not undergoing treatment with interferon gamma. Compared with control, severe infections were significantly reduced in patients treated with interferon gamma (relative risk, 0.46; 95% confidence interval, 0.29-0.73; P = .001). Interferon gamma treatment was associated with an absolute risk reduction of 31% and a number needed to treat of 3. Furthermore, compared with control, interferon gamma treatment reduced pulmonary infections (relative risk, 0.43; 95% confidence interval, 0.19-0.96; P = .04). Two studies with 172 patients with CGD were included in the antifungal drug analysis. Infections occurred in 4 of 69 patients (6%) treated with antifungals and in 17 of 103 patients (16%) not receiving treatment with antifungals. Compared with control, Aspergillus infections were not significantly reduced in patients treated with antifungals. No randomized prospective clinical trials of antibacterial prophylaxis in patients with CGD have been performed.
CONCLUSION: Despite the fact that interferon gamma prophylaxis seems to have a positive effect on severe infections, small sample sizes preclude definite conclusions. Further trials with interferon gamma and/or antifungal and antibiotics are necessary to optimize the treatment of CGD.

PMID: 27613462 [PubMed – in process]

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