Manish Butte

STR Profiling of HTLV-1-Infected Cell Lines.

February 2, 2018 By Manish Butte

STR Profiling of HTLV-1-Infected Cell Lines.

Methods Mol Biol. 2017;1582:143-154

Authors: Raimondi V, Minuzzo S, Ciminale V, D’Agostino DM

Abstract
Many investigations of the replication and pathogenesis of human T-cell leukemia virus type 1 (HTLV-1) employ chronically infected cell lines, cell lines stabilized from primary adult T-cell leukemia cells, and noninfected T-cell lines. The validity of data obtained from such studies depends on the unambiguous identification of each cell line, which can be performed by short-tandem-repeat (STR) profiling (DNA fingerprinting). While kit-based profiling represents the standard method for cell line authentication, not all labs have ready access to the required capillary electrophoresis equipment, and the costs of such tests can become substantial, especially if the cell lines are to be tested frequently. We analyzed DNA from a panel of HTLV-1-infected cell lines and noninfected T-cell lines using a commercial STR kit and then analyzed the same DNA for individual STR markers followed by nondenaturing polyacrylamide gel electrophoresis. This simplified method should facilitate routine confirmation of cell line identity in diverse laboratory settings.

PMID: 28357668 [PubMed – indexed for MEDLINE]

A 25-year surveillance of disseminated Bacillus Calmette-Guérin disease treatment in children in Southern Iran.

February 1, 2018 By Manish Butte

A 25-year surveillance of disseminated Bacillus Calmette-Guérin disease treatment in children in Southern Iran.

Medicine (Baltimore). 2017 Dec;96(52):e9035

Authors: Amanati A, Pouladfar G, Kadivar MR, Sanaei Dashti A, Jafarpour Z, Haghpanah S, Alborzi A

Abstract
Disseminated Bacillus Calmette-Guérin (BCG) disease is one of the most serious complications of BCG vaccination, mainly among immunocompromised children with high morbidity and mortality.Currently, there is no any consensus with regard to the standard regimen of antituberculosis (anti-TB) agents and duration of treatment in healthy or immunocompromised host in children. The aim of this study is to investigate the effect of various combination treatment strategies for disseminated BCG disease in children.In this cross-sectional study, the outcome of 3 different combination protocols was investigated in 59 patients.All patients were younger than 6 years old. Both possible immunocompetent and proven immunodeficient children were included in a period of 25 years (1991-2014) in a Nemazee referral teaching hospital.The minimum age was 1 month and the maximum was 60 months. The average age of patients was 8 months (8.26 ± 9.73). Out of 59 cases, 32 (54.2%) were female and 27 (45.8%) were male. Based on the primary work up, 52.5% of cases were classified as definite immunodeficient and 47.5% were classified as possible immunocompetent. Overall mortality rate was 50.8%. Mortality rate of disseminated BCG disease in immunocompetent and immunodeficient children was 28.6% and 71%, respectively. The mortality rate was not statistically different between patients treated with different treatment protocols. These results were not affected by immune status and the type of immunodeficiency.More than 2 anti-TB drugs combination will not change outcome of patient with disseminated BCG disease.

PMID: 29384896 [PubMed – in process]

Systematic investigation for underlying causes of recurrent infections in children: surveillance of primary immunodeficiency.

February 1, 2018 By Manish Butte

Systematic investigation for underlying causes of recurrent infections in children: surveillance of primary immunodeficiency.

Eur Ann Allergy Clin Immunol. 2017 Nov 21;:

Authors: Yousefzadegan S, Tavakol M, Abolhassani H, Nadjafi A, Mansouri S, Yazdani R, Azizi G, Negahdari B, Rezaei N, Aghamohammadi A

Abstract
Summary: Recurrent infections seem to be a common complaint in children who are referred to general practitioners and pediatricians offices. Detection of primary immunodeficiencies (PID) etiology is very important for achieving appropriate diagnosis and treatment of these patients. The absence of appropriate treatment could lead to subsequent complications, in a hospital inpatient and/or outpatient settings. This study was performed in a group of children with recurrent infections to identify patients with underlying PID. A cross-sectional study was designed to evaluate the final clinical diagnosis obtained in 100 pediatric patients with a history of recurrent infections referred to Children s Medical Center, Tehran, Iran, during one year (2011-2012). History taking and physical examination, complementary laboratory tests including immunological investigations were done to confirm the main causes of disease according to our previously published stepwise approach to recurrent infections. Among all studied patients, 21% (11 males and 10 females) were diagnosed to have PID. Parental consanguinity (p = 0.001) and soft tissue infections (p = 0.004) were significantly higher in PID group, comparing to other causes of recurrent infections. Gender and location of infections were also linked to the type of PID including antibody deficiency, combined immunodeficiency and phagocytosis disorders. The real rate of PID as a cause of recurrent infection appears to be much higher than what is generally considered in a se-lected group of pediatric patients; so, following the suggested stepwise guideline can im-prove timely diagnosis and appropriate treatment of these patients.

PMID: 29384110 [PubMed – as supplied by publisher]

Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.

February 1, 2018 By Manish Butte

Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.

J Clin Immunol. 2017 Oct;37(7):732-738

Authors: Arias AA, Perez-Velez CM, Orrego JC, Moncada-Velez M, Rojas JL, Wilches A, Restrepo A, Trujillo M, Garcés C, Arango-Ferreira C, González N, Oleaga-Quintas C, Fernández D, Isaza-Correa JM, Gongóra DE, Gonzalez-Loaiza D, Sierra JE, Casanova JL, Bustamante J, Franco JL

Abstract
PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia.
METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives.
RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70.
CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rβ1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.

PMID: 28865061 [PubMed – indexed for MEDLINE]

Successful sequential liver and haematopoietic stem cell transplantation in a child with CD40 ligand deficiency and Cryptosporidium-induced liver cirrhosis.

January 30, 2018 By Manish Butte

Successful sequential liver and haematopoietic stem cell transplantation in a child with CD40 ligand deficiency and Cryptosporidium-induced liver cirrhosis.

Transplantation. 2018 Jan 26;:

Authors: Quarello P, Tandoi F, Carraro F, Vassallo E, Pinon M, Romagnoli R, David E, Dell Olio D, Salizzoni M, Fagioli F, Calvo PL

Abstract
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a seven-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in one young adult to date.
METHODS: a closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft.
RESULTS: combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur.
CONCLUSIONS: hopefully this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child, will encourage others to adopt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies.

PMID: 29377874 [PubMed – as supplied by publisher]

Measurement of Typhim Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency.

January 30, 2018 By Manish Butte

Measurement of Typhim Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency.

Clin Exp Immunol. 2018 Jan 29;:

Authors: Evans C, Bateman E, Steven R, Ponsford M, Cullinane A, Shenton C, Duthie G, Conlon C, Jolles S, Huissoon AP, Longhurst HJ, Rahman T, Scott C, Wallis G, Harding S, Parker AR, Ferry BL

Abstract
Vaccine specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens but interpretation may be complicated. Typhim Vi®, a polysaccharide vaccine for Salmonella typhoid fever, maybe an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multicentre study describing the analytical and clinical performance of a Typhi Vi IgG ELISA calibrated to an affinity purified Typhi Vi IgG preparation. Intra- and inter-assay imprecision were low and the assay was linear between 7.4-574 U/mL (Slope=0.99-1.00; R2 >0.99). 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations >7.4U/mL, the concentration range was 7.7-167 U/mL. In antibody deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were <25 U/mL. In vaccinated normal healthy volunteers, the median concentration post vaccination was 107 U/mL (range 31-542U/mL). 8/8 (100%) had post vaccination concentration increases of at least 3-fold and 6/8 (75%) of at least 10-fold. In an antibody deficient population (n=23), only 30% had post vaccination concentration increases of at least 3-fold and 10% of at least 10-fold. The antibody responses to Pneumovax II and Typhim Vi® correlated. We conclude that IgG responses to Typhim Vi® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies. This article is protected by copyright. All rights reserved.

PMID: 29377063 [PubMed – as supplied by publisher]

Haploidentical stem cell transplantation in a boy with chronic granulomatous disease.

January 27, 2018 By Manish Butte

Haploidentical stem cell transplantation in a boy with chronic granulomatous disease.

Allergol Immunopathol (Madr). 2018 Jan 16;:

Authors: Regueiro-García A, Fariña-Nogueira S, Porto-Arceo JÁ, Couselo-Sánchez JM

Abstract
Chronic granulomatous disease is a primary immunodeficiency caused by mutations in any one of the five components of the NADPH oxidase in phagocytic leucocytes. This causes impaired microbial killing, which leads to severe life-threatening bacterial and fungal infections. Currently, allogenic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for chronic granulomatous disease, although gene therapy may provide a new therapeutic option for the treatment of patients with CGD. Haploidentical HSCT provides a potentially curative treatment option for patients who lack a suitably HLA-matched donor, but only a few cases have been reported in the literature. Herein, we report a boy with X-linked chronic granulomatous disease treated successfully by haploidentical HSCT with post-transplant cyclophosphamide using a treosulfan-based conditioning regimen.

PMID: 29373243 [PubMed – as supplied by publisher]

Leukocyte adhesion defect: An uncommon immunodeficiency.

January 27, 2018 By Manish Butte

Leukocyte adhesion defect: An uncommon immunodeficiency.

J Pak Med Assoc. 2018 Jan;68(1):119-122

Authors: Nigar S, Khan EA, Ahmad TA

Abstract
Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency disorder with autosomal recessive inheritance which is characterized by presence of a defect of phagocytic function resulting from a lack of leukocyte cell surface expression of b2 integrin molecules (CD11 and CD18) that are essential for chemotaxis. The classic symptoms of the disease are failure of separation of the umbilical cord and recurrent bacterial infections, which continue throughout life. We describe here two cases of infants who presented with characteristic history of recurrent infections, delayed separation of umbilical cord and marked leukocytosis.

PMID: 29371732 [PubMed – in process]

Photoletter to the editor: Atypical primary cutaneous mucormycosis of the scalp.

January 26, 2018 By Manish Butte

Photoletter to the editor: Atypical primary cutaneous mucormycosis of the scalp.

J Dermatol Case Rep. 2017 Dec 01;11(2):32-34

Authors: García-Sepúlveda R, Navarrete-Solís J, Villanueva-Lozano H, de J Treviño-Rangel R, González GM, Enríquez-Rojas J, Molina-Durazo J, Arenas-Guzmán R

Abstract
Mucormycosis of the scalp is a rare cutaneous presentation of the disease. It is also an unusual infection in children. We present the case of a 4-year-old girl with acute lymphoblastic leukemia, who presented with atypical cutaneous mucormycosis simulating an ecthyma gangrenosum lesion. Risk factors for the infection are diabetes, neoplastic diseases, immunosuppression in organ transplant recipients, and neutropenia. The cutaneos forms have been associated with trauma, burns and surgical wounds. First line treatment is amphotericin B. Posaconazole was recently approved to treat invasive mucormycosis. Surgical removal of the infected tissue is indicated.

PMID: 29367872 [PubMed]

Purinergic signaling in B cells.

January 24, 2018 By Manish Butte

Purinergic signaling in B cells.

Acta Biochim Pol. 2018 Jan 23;:

Authors: Przybyła T, Sakowicz-Burkiewicz M, Pawełczyk T

Abstract
Adenosine and adenosine triphosphate are involved in purinergic signaling which plays an important role in control of the immune system. Much data have been obtained regarding impact of purinergic signaling on dendritic cells, macrophages, monocytes and T lymphocytes, however less attention has been paid to purinergic regulation of B cells. This review summarizes present knowledge on ATP- and Ado-dependent signaling in B lymphocytes. Human B cells have been shown to express A1-AR, A2A-AR, A2B-AR and A3-AR and each subtype of P2 receptors. Surface of B cells exhibits two antagonistic ectoenzymatic pathways, one relies on constitutive secretion and resynthesis of ATP, while the second one depends on degradation of adenosine nucleotides to nucleosides and their subsequent degradation. Inactivated B cells remain under the suppressive impact of autocrine and paracrine Ado, whereas activated B lymphocytes increase ATP release and production. ATP protects B cells from Ado-induced suppression and exerts pro-inflammatory effect on the target tissues, and it is also involved in the IgM release. On the other hand, Ado synthesis is necessary for optimal development, implantation and maintenance of the plasmocyte population in bone marrow in the course of the primary immune response. Moreover, Ado plays an important role in immunoglobulin class switching, which is a key mechanism of humoral immune response. Disruption of purinergic signaling leads to severe disorders. Impairment of Ado metabolism is one of the factors responsible for common variable immunodeficiency. There are several lines of evidence that dysfunction of the immune system observed during diabetes may in part depend on disrupted ATP and Ado metabolism in the B cells.

PMID: 29360885 [PubMed – as supplied by publisher]