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primary immunodeficiency NOT human immunodeficiency virus; +35 new citations

May 30, 2014 By Manish Butte

35 new pubmed citations were retrieved for your search.
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primary immunodeficiency NOT human immunodeficiency virus

These pubmed results were generated on 2014/05/31

PubMed, a service of the National Library of Medicine, includes over 15 million
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primary immunodeficiency NOT human immunodeficiency virus; +27 new citations

May 1, 2014 By Manish Butte

27 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:

primary immunodeficiency NOT human immunodeficiency virus

These pubmed results were generated on 2014/05/01

SAPI Bowling Event

April 27, 2014 By Manish Butte

SAPI organized its first event, attended by many children and adults with PI. We rented a few lanes in at Bel-Mateo Bowl, just off El Camino Real in San Mateo, CA.

Prevention of human T-cell lymphotropic virus type 1 infection and adult T-cell leukemia/lymphoma.

April 2, 2014 By Manish Butte

Prevention of human T-cell lymphotropic virus type 1 infection and adult T-cell leukemia/lymphoma.

Recent Results Cancer Res. 2014;193:211-25

Authors: Yoshimitsu M, White Y, Arima N

Abstract
Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive peripheral T-cell malignancy that develops after long-term chronic infection with human T-cell lymphotropic virus type-1 (HTLV-1). Despite the recent advances in chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and supportive care, the prognosis for patients with ATL is one of the poorest among hematological malignancies; overall survival (OS) at 3 years is only 24 % in the more aggressive subtypes of ATLL. HTLV-1 is a human retrovirus infecting approximately 10-20 million people worldwide, particularly in southern and southeastern Japan, the Caribbean, highlands of South America, Melanesia, and Equatorial Africa. Despite this high frequency of human infection, only 2-5 % of HTLV-1-infected individuals develop ATLL. Three major routes of viral transmission have been established: (1) mother-to-child transmission through breast-feeding; (2) sexual transmission, predominantly from men to women; and (3) cellular blood components. Multiple factors (e.g., virus, host cell, and immune factors) have been implicated in the development of ATLL, although the underlying mechanisms of leukemogenesis have not been fully elucidated. No preventive vaccine against HTLV-1 is currently available, and interrupting the well-recognized primary modes of HTLV-1 transmission is the mainstay of ATLL prevention. Prevention of mother-to-child transmission through the replacement of breast-feeding has been shown to have the most significant impact on the incidence of HTLV-1 infection, and public health policies should consider the risk of malnutrition, especially in developing countries where malnutrition is the significant cause of infant mortality.

PMID: 24008301 [PubMed – indexed for MEDLINE]

primary immunodeficiency NOT human immunodeficiency virus; +30 new citations

April 1, 2014 By Manish Butte

30 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:

primary immunodeficiency NOT human immunodeficiency virus

These pubmed results were generated on 2014/04/01

Novel STAT3 Mutation Causing Hyper-IgE Syndrome: Studies of the Clinical Course and Immunopathology.

March 17, 2014 By Manish Butte

Novel STAT3 Mutation Causing Hyper-IgE Syndrome: Studies of the Clinical Course and Immunopathology.

J Clin Immunol. 2014 Mar 14;

Authors: Sundin M, Tesi B, Sund Böhme M, Bryceson YT, Pütsep K, Chiang SC, Thunberg S, Winiarski J, Wikström AC

Abstract
PURPOSE: Reporting a clinical case with a novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene resulting in autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES). Here we also had the opportunity to perform in-depth immunologic investigations to further understand the immunopathology of this primary immunodeficiency.
METHODS: The patient, a baby boy, was clinically assessed according to the scoring system developed by Grimbacher et al. and STAT3 was investigated by DNA sequencing. Immunologic work-up consisted of lymphocyte phenotyping and proliferation assays, measurement of soluble mediators and routine investigations.
RESULTS: According to the Grimbacher score the patient was likely to have AD-HIES and a novel heterozygous STAT3 mutation (c.1110-3C>A), causing a splice error, was identified. Lymphocyte phenotyping revealed decreased numbers of interleukin (IL)-17 producing T-helper lymphocytes and aberrant B-lymphocyte subsets. Proliferative in vitro lymphocyte responses against C. albicans, staphylococcal enterotoxins and pokeweed mitogen were supernormal at presentation, whereas only the elevated response to pokeweed mitogen persisted. The soluble mediators IL-5, -10, -12, -13, -15 and granulocyte colony stimulatory factor were elevated in serum.
CONCLUSION: A novel heterozygous STAT3 mutation causing defective splicing of exon 12 was identified. Lymphocyte phenotyping revealed deranged subpopulations. Despite the clinical picture with severe C. albicans and staphylococcal infections, the patient’s lymphocytes mounted responses to these pathogens. The hypereosinophilia and high immunoglobulin E levels might partly be explained by elevated IL-5 and -13 as a result of lack of negative feedback from defective STAT3 signaling.

PMID: 24627079 [PubMed – as supplied by publisher]

[Chronic myeloid leukemia in an adult with common variable immunodeficiency].

March 17, 2014 By Manish Butte

[Chronic myeloid leukemia in an adult with common variable immunodeficiency].

Rev Med Inst Mex Seguro Soc. 2014 Jan-Feb;52(1):94-7

Authors: O’Farrill-Romanillos PM, Galindo-Pacheco LV, Amaya-Mejía AS, Campos-Romero FH, Mendoza-Reyna LD, Pérez-Rocha F, Segura-Méndez NH

Abstract
BACKGROUND: Common variable immunodeficiency is a primary immunodeficiency, in which from 70 to 80 % of patients have tumors and 25 % of cases are associated with autoimmune diseases. Common variable immunodeficiency patients have a higher incidence of neoplasms, with a risk 12-18 times higher than the general population. There are few cases of common variable immunodeficiency patients with leukemia.
CLINICAL CASE: Female of 36 years old, with left upper quadrant pain, early satiety, weight loss of 8 kg in three months and splenomegaly. The complete blood count showed: leukocytosis 206 000/mL, with 8 % blasts, platelets 530 000/mL and hemoglobin 8 mg/dL. Abdominal ultrasound: 19??12 cm splenomegaly. Karyotype BCR/ABL IS 64.20 %, 100 % Philadelphia chromosome. The diagnosis was of chronic myeloid leukemia. Given the presence of recurrent respiratory tract infection, frequent diarrheas and reduced concentrations of IgG, IgM and IgA, common variable immunodeficiency was diagnosed and human immunoglobulin was used successfully.
CONCLUSIONS: The association between chronic myeloid leukemia and common variable immunodefficiency is unusual. Given the high frequency of hematological neoplasm in common variable immunodeficiency patients, we suggest that hematological patients with repeated infections and decreased concentrations of immunoglobulin be referred to an immunological evaluation.

PMID: 24625491 [PubMed – in process]

Gene therapy for wiskott-Aldrich syndrome–long-term efficacy and genotoxicity.

March 17, 2014 By Manish Butte

Gene therapy for wiskott-Aldrich syndrome–long-term efficacy and genotoxicity.

Sci Transl Med. 2014 Mar 12;6(227):227ra33

Authors: Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A, Rothe M, Modlich U, Beier R, Göhring G, Steinemann D, Fronza R, Ball CR, Haemmerle R, Naundorf S, Kühlcke K, Rose M, Fraser C, Mathias L, Ferrari R, Abboud MR, Al-Herz W, Kondratenko I, Maródi L, Glimm H, Schlegelberger B, Schambach A, Albert MH, Schmidt M, von Kalle C, Klein C

Abstract
Wiskott-Aldrich syndrome (WAS) is characterized by microthrombocytopenia, immunodeficiency, autoimmunity, and susceptibility to malignancies. In our hematopoietic stem cell gene therapy (GT) trial using a γ-retroviral vector, 9 of 10 patients showed sustained engraftment and correction of WAS protein (WASP) expression in lymphoid and myeloid cells and platelets. GT resulted in partial or complete resolution of immunodeficiency, autoimmunity, and bleeding diathesis. Analysis of retroviral insertion sites revealed >140,000 unambiguous integration sites and a polyclonal pattern of hematopoiesis in all patients early after GT. Seven patients developed acute leukemia [one acute myeloid leukemia (AML), four T cell acute lymphoblastic leukemia (T-ALL), and two primary T-ALL with secondary AML associated with a dominant clone with vector integration at the LMO2 (six T-ALL), MDS1 (two AML), or MN1 (one AML) locus]. Cytogenetic analysis revealed additional genetic alterations such as chromosomal translocations. This study shows that hematopoietic stem cell GT for WAS is feasible and effective, but the use of γ-retroviral vectors is associated with a substantial risk of leukemogenesis.

PMID: 24622513 [PubMed – in process]

T-cell activation discriminates subclasses of symptomatic primary humoral immunodeficiency diseases in adults.

March 17, 2014 By Manish Butte

T-cell activation discriminates subclasses of symptomatic primary humoral immunodeficiency diseases in adults.

BMC Immunol. 2014 Mar 12;15(1):13

Authors: Picat MQ, Thiébaut R, Lifermann F, Delbrel X, Adoue D, Wittkop L, Fauchais AL, Rispal P, Moreau JF, Viallard JF

Abstract
BACKGROUND: Symptomatic Primary Humoral Immunodeficiency Diseases (PHID) constitute a highly heterogeneous group of diseases characterized by a shared hypogammaglobulinemia, resulting in increased risk of recurrent or severe infections. Associations have been described with a variety of immunological abnormalities involving B and T-cell differentiation, T-cell activation and innate immunity. However, PHID discrimination remains based on B-lymphocyte abnormalities and other components of the immune system have not been sufficiently taken into account. We carried out unsupervised and supervised methods for classification in a cohort of 81 symptomatic PHID patients to evaluate the relative importance of 23 immunological parameters and to select relevant markers that may be useful for diagnosis and prognosis.
RESULTS: We identified five groups of patients, among which the percentage of PHID complications varied substantially. Combining the set of markers involved in PHID supported the existence of two distinct mechanisms associated with complications. Switched memory B-cell attrition and CD8+ HLA-DR + activated T-cell increase were the prominent abnormalities observed in PHID complications. Furthermore, in a subgroup of 57 patients with common variable immunodeficiency, the classification that added CD8+ HLA-DR + to the consensual EUROclass classification was better than the EUROclass model in predicting complications.
CONCLUSION: These results highlight the importance of T-cell activation that may improve discrimination of PHID patients in specific subgroups and help to identify patients with different clinical outcomes.

PMID: 24621280 [PubMed – as supplied by publisher]

First Report on the Moroccan Registry of Primary Immunodeficiencies: 15 Years of Experience (1998-2012).

March 17, 2014 By Manish Butte

First Report on the Moroccan Registry of Primary Immunodeficiencies: 15 Years of Experience (1998-2012).

J Clin Immunol. 2014 Mar 12;

Authors: Bousfiha AA, Jeddane L, El Hafidi N, Benajiba N, Rada N, El Bakkouri J, Kili A, Benmiloud S, Benhsaien I, Faiz I, Maataoui O, Aadam Z, Aglaguel A, Baba LA, Jouhadi Z, Abilkassem R, Bouskraoui M, Hida M, Najib J, Alj HS, Ailal F, For the Moroccan Society for Primary Immunodeficiencies (MSPID)

Abstract
PURPOSE: Primary immunodeficiencies (PIDs) are a large group of diseases characterized by susceptibility to infections. We provide the first comprehensive report on PIDs in Morocco, the epidemiological, clinical, etiological and outcome features which have never before been described.
METHODS: A national registry was established in 2008, grouping together data for PID patients diagnosed since 1998.
RESULTS: In total, 421 patients were diagnosed between 1998 and 2012. Parental consanguinity was common (recorded for 43.2 % of patients) and the median time to diagnosis was 2.0 years. Overall, 27.4 % of patients were considered to have well defined syndromes with immunodeficiency (48 cases of hyper-IgE syndrome and 40 of ataxia-telangiectasia); 22.7 % had predominantly antibody deficiencies (29 cases of agammaglobulinemia and 24 of CVID); 20.6 % had combined immunodeficiencies (37 cases of SCID and 26 of MHC II deficiencies) and 17.5 % had phagocyte disorders (14 cases of SCN and 10 of CGD). The principal clinical signs were lower respiratory tract infections (60.8 %), skin infections (33.5 %) and candidiasis (26.1 %). Mortality reached 28.8 %, and only ten patients underwent bone marrow transplantation. We analyzed the impact on mortality of residence, family history, parental consanguinity, date of diagnosis and time to diagnosis, but only date of diagnosis had a significant effect.
CONCLUSIONS: The observed prevalence of PID was 0.81/100,000 inhabitants, suggesting considerable underdiagnosis and a need to increase awareness of these conditions in Morocco. The distribution of PIDs was different from that reported in Western countries, with a particularly high proportion of SCID, MHC II deficiencies, hyper-IgE syndrome and autosomal recessive agammaglobulinemia. However, we have now organized a national network, which should improve diagnosis rates in remote regions.

PMID: 24619622 [PubMed – as supplied by publisher]