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Defective functions of polymorphonuclear neutrophils in patients with common variable immunodeficiency.

Immunol Res. 2014 Jul 1;

Authors: Casulli S, Coignard-Biehler H, Amazzough K, Shoai-Tehrani M, Bayry J, Mahlaoui N, Elbim C, Kaveri SV

Abstract
Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency condition with alterations in T cell regulation and function, dendritic and B-cell compartment and represents the most frequent cause of symptomatic primary immunodeficiency. We addressed whether CVID is associated with abnormalities in the polymorphonuclear neutrophil (PMN) compartment, an important component of innate immunity and plays a key role in host defenses against invading microorganisms. We used flow cytometry to examine PMN phenotypic and functional abnormalities in CVID patients, using whole-blood conditions in order to avoid artifacts due to isolation procedures. We demonstrated that PMN from CVID patients displays, at resting state, a decreased expression of CD15, CD11b and CD16b, which might be related to an abnormality in neutrophil maturation. In addition, these neutrophils exhibit a decrease in degranulation, phagocytosis and reactive oxygen species production, as well as an increased death by apoptosis. These PMN abnormalities observed in CVID patients could result in an increased risk for recurrent bacterial infections.

PMID: 24981124 [PubMed – as supplied by publisher]

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Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease.

J Allergy Clin Immunol. 2014 Jun 27;

Authors: Magnani A, Brosselin P, Beauté J, de Vergnes N, Mouy R, Debré M, Suarez F, Hermine O, Lortholary O, Blanche S, Fischer A, Mahlaoui N

Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is a rare phagocytic disorder that results in not only infections but also potentially severe inflammatory manifestations that can be difficult to diagnose and treat.
OBJECTIVE: To describe inflammatory manifestations in a single-center cohort of patients with CGD.
METHODS: Medical records of patients treated at Necker-Enfants Malades Hospital (Paris, France) between 1968 and 2009 and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH) were retrospectively reviewed.
RESULTS: In a study population of 98 patients, a total of 221 inflammatory episodes were recorded in 68 individuals (69.4%). The incidence rate of inflammatory episodes was 0.15 per person-year (0.18 in patients with X-linked [XL] CGD and 0.08 in patients with autosomal-recessive [AR] CGD). The most commonly affected organs were the gastrointestinal tract (in 88.2% of the patients), lungs (26.4%), the urogenital tract (17.6%), and eyes (8.8%). Inflammation at other sites (the skin, central nervous system, and tympanum) and autoimmune manifestations (lupus, arthritis, etc) were recorded in 19.1% and 10.3% of the patients, respectively. Granuloma was found in 50% of the 44 histological analyses reviewed. The risk of inflammatory episodes was 2-fold higher in patients with XL-CGD than in patients with AR-CGD (relative risk, 2.22; 95% CI, 1.43-3.46).
CONCLUSIONS: Patients with XL-CGD have a higher risk of developing inflammatory episodes than do patients with AR-CGD. Although the most commonly affected organ is the gastrointestinal tract, other sites can be involved, making the management of patients with CGD a complex, multidisciplinary task.

PMID: 24985400 [PubMed – as supplied by publisher]

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Chronic granulomatous disease with pulmonary mass-like opacities secondary to hypersensitivity pneumonitis: a case report.

J Med Case Rep. 2014 Jul 2;8(1):242

Authors: Katsuya Y, Hojo M, Kawai S, Kawai T, Onodera M, Sugiyama H

Abstract
INTRODUCTION: Chronic granulomatous disease, one of the primary immunodeficiency syndromes, is characterized by failure of phagocytic capacity due to loss of reactive oxygen species production, as well as formation of granulomas in organs. Clinically, dysregulated inflammation by excessive cytokine production due to loss of reactive oxygen species production is suggested as a cause of noninfectious inflammatory problems such as chronic granulomatous disease colitis. We experienced a rare case of a patient with chronic granulomatous disease with unique pathological and radiological presentations of hypersensitive pneumonitis, which to our knowledge has never been previously reported.
CASE PRESENTATION: A 20-year-old Japanese man with chronic granulomatous disease was referred due to cough and abnormal chest imaging findings. Computed tomography of his chest showed diffuse, bilateral, centrilobular nodules and multiple mass lesions in lower lobes that do not fit a common image of hypersensitivity pneumonitis. Pathological findings of both nodules and mass lesions on surgical lung biopsy were homogeneous, and excessive granulomas in the bronchioles and alveolar duct as well as lymphocytic alveolitis were seen, all consistent with hypersensitivity pneumonitis. The radiological and laboratory abnormalities did not improve after antigen avoidance; however, they disappeared after high-dose steroid therapy.
CONCLUSIONS: When we encounter a case of hypersensitive pneumonitis showing atypical pulmonary mass-like opacities in a patient with chronic granulomatous disease, we should consider hyperinflammatory status and excessive granuloma formation of chronic granulomatous disease and start with high-dose steroid therapy as treatment.

PMID: 24989247 [PubMed – as supplied by publisher]

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Characterization of five newly isolated bacteriophages active against Pseudomonas aeruginosa clinical strains.

Folia Microbiol (Praha). 2014 Jul 4;

Authors: Kwiatek M, Mizak L, Parasion S, Gryko R, Olender A, Niemcewicz M

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections, especially in patients with immunodeficiency. It exhibits multiple mechanisms of resistance, including efflux pumps, antibiotic modifying enzymes and limited membrane permeability. The primary reason for the development of novel therapeutics for P. aeruginosa infections is the declining efficacy of conventional antibiotic therapy. These clinical problems caused a revitalization of interest in bacteriophages, which are highly specific and have very effective antibacterial activity as well as several other advantages over traditional antimicrobial agents. Above all, so far, no serious or irreversible side effects of phage therapy have been described. Five newly purified P. aeruginosa phages named vB_PaeM_WP1, vB_PaeM_WP2, vB_PaeM_WP3, vB_PaeM_WP4 and vB_PaeP_WP5 have been characterized as potential candidates for use in phage therapy. They are representatives of the Myoviridae and Podoviridae families. Their host range, genome size, structural proteins and stability in various physical and chemical conditions were tested. The results of these preliminary investigations indicate that the newly isolated bacteriophages may be considered for use in phagotherapy.

PMID: 24993480 [PubMed – as supplied by publisher]

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Primary immunodeficiency diagnosed at autopsy: a case report.

BMC Res Notes. 2014;7(1):425

Authors: Walong E, Rogena E, Sabai D

Abstract
BACKGROUND: DiGeorge syndrome may manifest as severe immunodeficiency diagnosed at infancy. The diagnosis of primary immunodeficiency is based on characteristic clinical features, immunophenotyping by flow cytometry, molecular diagnostics and functional lymphocyte evaluation. At autopsy, gross evaluation, conventional histology and immunohistochemistry may be useful for the diagnosis of primary immunodeficiency. This case report illustrates the application of autopsy and immunohistochemistry in the diagnosis of DiGeorge syndrome.
CASE PRESENTATION: A four-month-old African female infant died while undergoing treatment at Kenyatta National Hospital, a Referral and Teaching Hospital in Nairobi, Kenya. She presented with a month’s history of recurrent respiratory infections, a subsequent decline in the level of consciousness and succumbed to her illness within four days. Her two older siblings died following similar circumstances at ages 3 and 5 months respectively. Autopsy revealed thymic aplasia, bronchopneumonia and invasive brain infection by Aspergillus species. Microbial cultures of cerebrospinal fluid, jejunal contents, spleen and lung tissue revealed multi drug resistant Klebsiella spp, Pseudomonas spp, Serratia spp and Escherichia coli. Immunohistochemistry of splenic tissue obtained from autopsy confirmed reduction of T lymphocytes.
CONCLUSION: Use of immunohistochemistry on histological sections of tissues derived from autopsy is a useful adjunct for post mortem diagnosis of DiGeorge syndrome.

PMID: 24996427 [PubMed – in process]

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Respiratory infection and primary immune deficiency – what does the general physician need to know?

J R Coll Physicians Edinb. 2014 Jun;44(2):149-55

Authors: Lear S, Condliffe A

Abstract
This review, based on a talk given at the RCPE Respiratory Medicine Symposium 2014, outlines the clinical spectrum of immune deficiency – antibody (B cell) deficiency, T cell defects and innate/phagocytic disorders – and discusses the relevant clinical presentations, investigations and treatments, focusing particularly on the management of adults with recurrent respiratory infections. It describes when to suspect a primary immunodeficiency, the first-line investigations to perform and the triggers that should prompt referral for further specialist opinion. The paper concludes with a look at a novel primary immunodeficiency, Activated PI3 Kinase Delta Syndrome (APDS).

PMID: 24999779 [PubMed – in process]

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MHC class I and II deficiencies.

J Allergy Clin Immunol. 2014 Jul 4;

Authors: Hanna S, Etzioni A

Abstract
Deficiencies of MHC complex class I or II are rare primary immunodeficiencies, both of which are inherited in an autosomal recessive pattern. MHC class II deficiency is a prototype of a disease of gene regulation. Defects in transacting regulatory factors required for expression of MHC class II genes, rather than the genes themselves, are responsible for the disease phenotype. The affected genes are known to encode 4 distinct regulatory factors controlling transcription of MHC class II genes. These transacting factors are the class II transactivator and 3 subunits of regulatory factor X (RFX): RFX containing ankyrin repeats (RFXANK), the fifth member of the RFX family (RFX5), and RFX-associated protein (RFXAP). Mutations in one of each define 4 distinct complementation groups termed A, B, C, and D, respectively. MHC class I deficiency is extremely rare and has been reported in less than 30 patients worldwide. Here we review the clinical, genetic, and molecular features that characterize these primary immunodeficiencies and discuss therapy options. Beyond the description of MHC class I and II deficiencies, their discovery has fascinated scientists and clinicians because of their ability to reveal the molecular basis of MCH regulation.

PMID: 25001848 [PubMed – as supplied by publisher]

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Sarcoidosis and common variable immunodeficiency: similarities and differences.

Semin Respir Crit Care Med. 2014 Jun;35(3):330-5

Authors: Verbsky JW, Routes JM

Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency that is characterized by hypogammaglobulinemia and poor/absent specific antibody production. Granulomatous and lymphocytic interstitial lung disease (GLILD) is an increasingly recognized complication of CVID, occurring in 10 to 20% of patients. GLILD is characterized by non-necrotizing granuloma, lymphocytic interstitial pneumonitis and follicular bronchiolitis-histological patterns that are typically present in the same biopsy. GLILD is a multisystem disease and is frequently accompanied by diffuse adenopathy, splenomegaly, and extrapulmonary granulomatous disease most commonly in the lymph nodes, spleen, liver, and gastrointestinal tract. The presence of noncaseating granuloma in the lung along with some of the extrapulmonary features of GLILD may lead to an incorrect diagnosis of sarcoidosis. However, GLILD differs from sarcoidosis in several important ways including mode of presentation, extrapulmonary manifestations, radiographic abnormalities on high-resolution computed tomography scan of the chest, and laboratory features (serum immunoglobulins, bronchoalveolar lavage, and histopathology). The misdiagnosis of sarcoidosis in a patient with CVID and GLILD can lead to inappropriate treatment and increase the morbidity and mortality of the disorder.

PMID: 25007085 [PubMed – in process]

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Severe combined immunodeficiency in Brazil: management, prognosis, and BCG-associated complications.

J Investig Allergol Clin Immunol. 2014;24(3):184-91

Authors: Mazzucchelli JT, Bonfim C, Castro GG, Condino-Neto AA, Costa NM, Cunha L, Dantas EO, Dantas VM, de Moraes-Pinto MI, Fernandes JF, Goes HC, Goudouris E, Grumach AS, Guirau LM, Kuntze G, Mallozzi MC, Monteiro FP, Moraes LS, Nudelman V, Pinto JA, Rizzo MC, Porto-Neto AC, Roxo-Junior P, Ruiz M, Rullo VE, Seber A, Takano OA, Tavares FS, Toledo E, Vilela MM, Costa-Carvalho BT

Abstract
BACKGROUND: Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency. The objectives of this study were to analyze the diagnosis, treatment, and prognosis of SCID in Brazil and to document the impact of BCG vaccine.
METHODS: We actively searched for cases by contacting all Brazilian referral centers.
RESULTS: We contacted 23 centers and 70 patients from 65 families. Patients were born between 1996 and 2011, and 49 (70%) were male. More than half (39) of the diagnoses were made after 2006. Mean age at diagnosis declined from 9.7 to 6.1 months (P = .058) before and after 2000, respectively, and mean delay in diagnosis decreased from 7.9 to 4.2 months (P = .009). Most patients (60/70) were vaccinated with BCG before the diagnosis, 39 of 60 (65%) had complications related to BCG vaccine, and the complication was disseminated in 29 of 39 (74.3%). Less than half of the patients (30, 42.9%) underwent hematopoietic stem cell transplantation (HSCT). Half of the patients died (35, 50%), and 23 of these patients had not undergone HSCT. Disseminated BCG was the cause of death, either alone or in association with other causes, in 9 of 31 cases (29%, no data for 4 cases).
CONCLUSIONS: In Brazil, diagnosis of SCID has improved over the last decade, both in terms of the number of cases and age at diagnosis, although a much higher number of cases had been expected. Mortality is higher than in developed countries. Complications of BCG vaccine are an important warning sign for the presence of SCID and account for significant morbidity during disease progression.

PMID: 25011356 [PubMed – in process]

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