Research

Related Articles

Hemophagocytic lymphohistiocytosis in imported pediatric visceral leishmaniasis in a nonendemic area.

J Pediatr. 2014 Jul;165(1):147-153.e1

Authors: Bode SF, Bogdan C, Beutel K, Behnisch W, Greiner J, Henning S, Jorch N, Jankofsky M, Jakob M, Schmid I, Veelken N, Vraetz T, Janka G, Ehl S, Lehmberg K

Abstract
OBJECTIVES: To describe characteristics of visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis (HLH) with focus on diagnostic clues and pitfalls, including the frequency of central nervous system (CNS) involvement, and to determine the efficacy of liposomal amphotericin B (L-AmB).
STUDY DESIGN: We retrospectively analyzed clinical and laboratory features, diagnostic procedures, and treatment of 13 patients with HLH with imported visceral leishmaniasis, reported to the German HLH reference center (1999-2012).
RESULTS: The spectrum of presentations was indistinguishable from patients with hereditary HLH or with acquired HLH because of infections with other pathogens. In 8 patients, disease onset occurred before the age of 2 years, coinciding with the typical age of manifestation of primary HLH. Two patients had mild nonspecific CNS findings. Misleading antiviral IgM (n = 6) and autoantibodies (n = 2) led to inaccurate interpretation of the etiology of HLH, sometimes with inappropriate therapeutic consequences. False negative results for Leishmania were obtained by initial bone marrow microscopy in 6/13, serology in 1/12, bone marrow culture in 2/5, and polymerase chain reaction of peripheral blood in 1/3 patients, and all bone marrow samples tested were Leishmania-positive by polymerase chain reaction (n = 7). L-AmB was administered to 12 patients, 5 of whom had no prior HLH-directed immunosuppressive therapy; sodium stibogluconate was administered to 1 patient. Persistent remission was achieved in 11 cases. Two patients required repeated or prolonged L-AmB therapy.
CONCLUSIONS: Awareness of diagnostic pitfalls may save patients from unnecessary toxic treatment. CNS involvement is rare. L-AmB shows efficacy in visceral leishmaniasis-associated HLH.

PMID: 24797953 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Tuberculoma in the medulla oblongata and medulla spinalis: two case reports.

Balkan Med J. 2013 Dec;30(4):442-5

Authors: Gülşen S, Caner H

Abstract
BACKGROUND: Central nervous system tuberculosis remains a prevalent problem in developing countries. Also, this disease has been an important problem in developed countries due to the increased incidence of acquired immunodeficiency syndrome. Tuberculosis of the central nervous system is seen in 10% of immunocompetent patients with primary tuberculosis.
CASE REPORT: We report two patients with tuberculoma in the central nervous system. The first case had a lesion located in the medulla oblongata, and the second case had a lesion in the medulla spinalis between the 5th cervical and 1st thoracic vertebral level. Both of these patients underwent surgery.
CONCLUSION: CNS tuberculomas may not always show typical magnetic resonance imaging (MRI) signs, but when a neurosurgeon encounters a brown-yellow rubber-like lesion that is easily extirpated from the glial tissue, tuberculoma should be considered; anti-tuberculous and corticosteroid therapy should be initiated as soon as possible to prevent meningitis and the immune-mediated destructive effects of tuberculosis on the CNS. Whether or not anti-tuberculous therapy is continued can be decided upon by following definitive pathologic diagnosis.

PMID: 25207157 [PubMed]

Powered by WPeMatico

Progress in gene therapy for primary immunodeficiencies using lentiviral vectors.

Curr Opin Allergy Clin Immunol. 2014 Sep 8;

Authors: Sauer AV, Di Lorenzo B, Carriglio N, Aiuti A

Abstract
PURPOSE OF REVIEW: This review gives an overview over the most recent progress in the field of lentiviral gene therapy for primary immunodeficiencies (PIDs). The history and state-of-the-art of lentiviral vector development are summarized and the recent advancements for a number of selected diseases are reviewed in detail. Past retroviral vector trials for these diseases, the most recent improvements of lentiviral vector platforms and their application in preclinical development as well as ongoing clinical trials are discussed.
RECENT FINDINGS: Main focus is on the preclinical studies and clinical trials for the treatment of Wiskott-Aldrich syndrome, chronic granulomatous disease, adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID) and X-linked severe combined immunodeficiency with lentiviral gene therapy.
SUMMARY: Gene therapy for PIDs is an effective treatment, providing potential long-term clinical benefit for affected patients. Substantial progress has been made to make lentiviral gene therapy platforms available for a number of rare genetic diseases. Although many ongoing gene therapy trials are based on ex-vivo approaches with autologous hematopoietic stem cells, other approaches such as in-vivo gene therapy or gene-repair platforms might provide further advancement for certain PIDs.

PMID: 25207699 [PubMed – as supplied by publisher]

Powered by WPeMatico

Efficacy of intravenous immunoglobulin treatment in immunocompromised children with H1N1 influenza: A clinical observation.

Clin Respir J. 2014 Sep 5;

Authors: Gokturk B, Pekcan S, Guner SN, Artac H, Keles S, Kirac M, Reisli I

Abstract
BACKGROUND: The appropriate treatment of pandemic H1N1 influenza which was first identified in April 2009 in Mexico is insufficient especially for immunocompromised patients. We aimed to evaluate the features and prognostic factors of the children with H1N1, especially immunocompromised ones, and whether if intravenous immunoglobulin G (IVIG) replacement could aid for a better outcome.
METHODS: Twenty one hospitalized children with laboratory-confirmed H1N1 were evaluated retrospectively. Data were extracted from files and electronic medical records.
RESULTS: The median age was 37 (1-216) months; 62% of them were under 5 year of age and 71.4% had one or more underlying disorders. Main symptoms were high fever, cough, fatigue and vomitting. Lower respiratory tract manifestations were seen in 66.6% of children. Mortality rate was 4.7%. The patient who died had the lowest lymphocyte (100/mm(3) ), thrombocyte (21000/mm(3) ) and highest blood urea nitrogen (87mg/dl) levels. Fifty eight percent of evaluated patients had one of the primary immunodeficiency disorders. Surprisingly, none of the 6 patients with primary immunodeficiency who are on regular IVIG replacement needed intensive care unit and died. Although median durations of cough, fever and hospitalization were lower, they did not change statistically according to get IVIG replacement regularly (P=0.47, 0.97, 0.09, respectively).
CONCLUSION: Our study is important while it is the first one which shows the course of primary immunodeficient children with H1N1 infection who were on regular IVIG replacement. A trial of high dose IVIG may be a useful adjunctive therapy in severe H1N1 influenza, particularly in the immunocompromised patients.

PMID: 25196245 [PubMed – as supplied by publisher]

Powered by WPeMatico

[Common variable immunodeficiency (CVID): Clinical and immunological features of 29 Algerian patients.]

Pathol Biol (Paris). 2014 Sep 4;

Authors: Tahiat A, Djidjik R, Boushaki S, Cherguelaïne K, Gharnaout M, Boumedine S, Smati L, Benhalla N, Atek A, Baghriche M, Zidouni N, Ghaffor M

Abstract
PURPOSE: Common variable immunodeficiency (CVID) is the commonest symptomatic primary immunodeficiency. It is characterized by a defect of antibody production, recurrent respiratory tract infections and increased occurrence of auto-immune discords and lymphoproliferative disease.
METHODS: This retrospective study was conducted on 29 patients fulfilling the classical CVID definition. Blood tests included immunoglobulin measurement and lymphocyte subpopulations phenotyping.
RESULTS: This study includes 29 patients. The mean age at diagnosis was 23years. Recurrent upper and lower bacterial respiratory tract infections were common in almost all patients. Five patients developed auto-immune conditions and six had lymphoproliferative disease. Decreased IgG was found in almost all patients. Low IgA and IgM levels were found in 89.6 % and 65.5 % of cases respectively. Abnormal T and/or B phenotype was found in 75 % of cases; the most common abnormalities were decreased circulating B (54.2 %) and T CD4+ (41.7 %) cells and inversion of the CD4/CD8 ratio (70.8 %). Patients with decreased circulating B and T CD4+ cells were significantly more likely to have auto-immune cytopenias and lymphoproliferative disease.
CONCLUSIONS: Our study confirms the heterogeneity of CVID. A patient’s classification is necessary to define homogeneous groups of patients and to characterize specific molecular abnormalities in each group.

PMID: 25200463 [PubMed – as supplied by publisher]

Powered by WPeMatico

Related Articles

Evaluation of T and B lymphocyte function in clinical practice using a flow cytometry based proliferation assay.

Clin Immunol. 2014 Aug;153(2):332-42

Authors: Marits P, Wikström AC, Popadic D, Winqvist O, Thunberg S

Abstract
The golden standard for functional evaluation of immunodeficiencies is the incorporation of [(3)H]-thymidine in a proliferation assay stimulated with mitogens. Recently developed whole blood proliferation assays have the advantage of parallel lymphocyte lineage analysis and in addition provide a non-radioactive alternative. Here we evaluate the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) in a comparison with [(3)H]-thymidine incorporation in four patients with severe combined immunodeficiency. The threshold for the minimum number of lymphocytes required for reliable responses in FASCIA is determined together with reference values from 100 healthy donors when stimulated with mitogens as well as antigen specific stimuli. Finally, responses against PWM and SEA+SEB stimuli are conducted with clinically relevant immunomodulatory compounds. We conclude that FASCIA is a rapid, stable and sensitive functional whole blood assay that requires small amounts of whole blood that can be used for reliable assessment of lymphocyte reactivity in patients.

PMID: 24909732 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

“Warning signs” of primary immunodeficiency among patients with periprosthetic joint infection.

J Appl Biomater Funct Mater. 2014;12(2):e65-e69

Authors: Diaz-Ledezma C, Baker J, Parvizi J

Abstract
PURPOSE: The use of ten clinical “warning signs” has been suggested as a screening tool to identify patients that may have primary immunodeficiency (PID) conditions in adulthood. This study aimed to evaluate the presence of these “warning signs” among a cohort of patients with periprosthetic joint infections (PJI), in order to detect those cases that may have had a PID contributing to development of infection.
METHODS: A descriptive study using our institutional PJI database was conducted. 185 patients with more than 15 medical consultations in our healthcare network before the diagnosis of PJI were considered eligible for the study. The presence of the “warning signs” was retrospectively evaluated using medical records.
RESULTS: Twenty-seven patients (14.5%) presented with one or more “warning signs” of PID; however, 24 of the individuals had another immunocompromising condition and were thought to suffer secondary immunodeficiency. Among the remaining 3 patients, PID was confirmed in 1 individual who was found to have hypogammaglobulinemia.
CONCLUSIONS: It appears that some patients who develop PJI could suffer from a primary immunodeficiency status that may be detected using “warning signs” questionnaire. The administration of these questions to patients with multiple infections may lead to identification of a primary immunodeficiency status which may in turn influence the outcome of elective arthroplasty or PJI, when develops.

PMID: 25191844 [PubMed – as supplied by publisher]

Powered by WPeMatico

Related Articles

Emerging roles of store-operated Ca²⁺ entry through STIM and ORAI proteins in immunity, hemostasis and cancer.

Channels (Austin). 2013 Sep-Oct;7(5):379-91

Authors: Bergmeier W, Weidinger C, Zee I, Feske S

Abstract
Store-operated Ca(2+) entry (SOCE) is an important Ca(2+) influx pathway, which is defined by the fact that depletion of intracellular Ca(2+) stores, mainly the endoplasmic reticulum (ER), triggers the opening of Ca(2+) channels in the plasma membrane. The best characterized SOC channel is the Ca(2+) release-activated Ca(2+) (CRAC) channel, which was first described in cells of the immune system but has since been reported in many different cell types. CRAC channels are multimers of ORAI family proteins, of which ORAI1 is the best characterized. They are activated by stromal interaction molecules (STIM) 1 and 2, which respond to the depletion of intracellular Ca(2+) stores with oligomerization and binding to ORAI proteins. The resulting SOCE is critical for the physiological function of many cell types including immune cells and platelets. Recent studies using cell lines, animal models and primary cells from human patients with defects in SOCE have highlighted the importance of this Ca(2+) entry mechanism in a variety of pathophysiological processes. This review focuses on the role of SOCE in immunity to infection, allergy, hemostasis and cancer.

PMID: 23511024 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Sheep CD34+ amniotic fluid cells have haematopoietic potential and engraft after autologous in utero transplantation.

Stem Cells. 2014 Sep 3;

Authors: Shaw SW, Blundell MP, Pipino C, Shangaris P, Maghsoudlou P, Ramachandra DL, Georgiades F, Boyd M, Thrasher AJ, Porada CD, Almeida-Porada G, Cheng PJ, David AL, De Coppi P

Abstract
Unmatched allogeneic in utero stem cell transplantation (IUSCT) produces poor engraftment unless the fetus has congenital immunodeficiency, probably because of maternal and fetal immune responses to injected cells. We studied the functional haematopoietic potential of transduced GFP+ sheep amniotic fluid (AF) stem cells, before and after autologous IUSCT. CD34+ cells were selected from first trimester sheep AF, transduced overnight and injected intravenously into NOD-SCID-gamma (NSG) mice. At 3 months primary recipient bone marrow (BM) was injected into secondary NSG recipients. GFP+ cells were detected in the haematopoietic organs and peripheral blood of primary and secondary recipients at 3 months. Autologous IUSCT (transduced GFP+CD34+AF) was performed in fetal sheep. Six months postnatally, lamb BM was injected into secondary NSG recipients. GFP+ cells were detected in the peripheral blood of primary and secondary recipients. This confirms the haematopoietic potential of AF stem cells supporting the concept of autologous IUSCT to treat congenital haematopoietic disease. Stem Cells 2014.

PMID: 25186828 [PubMed – as supplied by publisher]

Powered by WPeMatico

Interstitial Lung Disease with Multiple Microgranulomas in Chronic Granulomatous Disease.

J Clin Immunol. 2014 Sep 4;

Authors: Kawai T, Watanabe N, Yokoyama M, Nakazawa Y, Goto F, Uchiyama T, Higuchi M, Maekawa T, Tamura E, Nagasaka S, Hojo M, Onodera M

Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that is characterized by susceptibility to bacterial and fungal infections. CGD patients also suffer from immune regulatory disorders, such as CGD-associated bowel inflammation with granuloma, which could be caused by excessive inflammation without demonstrable infection.
PURPOSE: We investigated the clinical manifestation of interstitial lung disease (ILD) resulting from excessive inflammation in X-linked CGD patients.
METHODS: Pulmonary CT images and testing of serum KL-6 levels were performed to assess ILD in the patients. For this study, patients with pulmonary lesions due to demonstrable infections were excluded from among ILD patients.
RESULTS: Among 33 CGD patients, four developed ILD; they had increased reticulo-nodular opacities on CT images and elevated serum KL-6 levels. Histopathological examinations revealed multiple homogeneous microgranulomas in the lesions of inflammatory cell infiltration. Mononuclear cells obtained from their pulmonary lesions produced higher amounts of inflammatory cytokines than the peripheral blood mononuclear cells of CGD patients, suggesting that the only infiltrating cells in the pulmonary lesions were activated and produced large amounts of inflammatory cytokines in ILD patients. Interestingly, an anti-inflammatory drug, such as a corticosteroid or thalidomide, but not anti-bacterial or anti-fungal drugs, improved CT image findings and reduced their KL-6 levels.
CONCLUSIONS: CGD patients’ daily exposures to inhaled antigens may induce excessive reactions with the production of inflammatory cytokines leading to the development of ILD with multiple microgranulomas, which could be due to an inadequate production of reactive oxygen species in CGD.

PMID: 25186973 [PubMed – as supplied by publisher]

Powered by WPeMatico