Papers by Abdullah Alangari
Introduction: As manuka honey (MH) exhibits immunoregulatory and anti-staphylococcal activities, ... more Introduction: As manuka honey (MH) exhibits immunoregulatory and anti-staphylococcal activities, we aimed to investigate if it could be effective in the treatment of atopic dermatitis (AD). Methods: Adult volunteers with bilateral AD lesions were asked to apply MH on one site overnight for seven consecutive days and leave the contralateral site untreated as possible. Three Item Severity score was used to evaluate the response. Skin swabs were obtained from both sites before and after treatment to investigate the presence of staphylococci and enterotoxin production. In addition, the ability of MH and its methanolic and hexane extracts to down regulate IL4-induced CCL26 protein release from HaCaT cells was evaluated by enzyme linked immunosorbent assay. Also, the ability of MH to modulate calcium ionophore-induced mast cell degranulation was assessed by enzyme immunoassay. Results: In 14 patients, AD lesions significantly improved post MH treatment versus pre-treatment as compared to control lesions. No significant changes in the skin staphylococci were observed after day 7, irrespective of honey treatment. Consistent with the clinical observation, MH significantly down regulated IL4-induced CCL26 release from HaCaT cells in a dose-dependent manner. This effect was partially lost, though remained significant, when methanolic and hexane extracts of MH were utilized. In addition, mast cell degranulation was significantly inhibited following treatment with MH. Conclusions: MH is potentially effective in the treatment of AD lesions based on both clinical and cellular studies through different mechanisms. This needs to be confirmed by randomized and controlled clinical trials.
Urticarial vasculitis is an uncommon from of cutaneous vasculitis and is extremely rare to presen... more Urticarial vasculitis is an uncommon from of cutaneous vasculitis and is extremely rare to present during childhood, especially in boys. It typically presents with multiple systemic inflammatory manifestations. Skin biopsy is needed to confirm the diagnosis. In this report a 10 years old Saudi boy with prolonged urticarial rash, fever, and arthritis is presented. His skin biopsy was consistent with leukocytoclastic vasculitis. His treatment course with several anti-inflammatory agents is described.
Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort
Genetics in medicine : official journal of the American College of Medical Genetics, Jan 3, 2015
Dysmorphology syndromes are among the most common referrals to clinical genetics specialists. Ina... more Dysmorphology syndromes are among the most common referrals to clinical genetics specialists. Inability to match the dysmorphology pattern to a known syndrome can pose a major diagnostic challenge. With an aim to accelerate the establishment of new syndromes and their genetic etiology, we describe our experience with multiplex consanguineous families that appeared to represent novel autosomal recessive dysmorphology syndromes at the time of evaluation. Combined autozygome/exome analysis of multiplex consanguineous families with apparently novel dysmorphology syndromes. Consistent with the apparent novelty of the phenotypes, our analysis revealed a strong candidate variant in genes that were novel at the time of the analysis in the majority of cases, and 10 of these genes are published here for the first time as novel candidates (CDK9, NEK9, ZNF668, TTC28, MBL2, CADPS, CACNA1H, HYAL2, CTU2, and C3ORF17). A significant minority of the phenotypes (6/31, 19%), however, were caused by ge...
Intravenous immunoglobulin utilization in a tertiary care teaching hospital in Saudi Arabia
Saudi medical journal, 2008
To evaluate the effect of intravenous immunoglobulin IVIG utilization at King Khalid University H... more To evaluate the effect of intravenous immunoglobulin IVIG utilization at King Khalid University Hospital, an 850 bed tertiary care academic center, over a-3-year period. Patients who received IVIG in the period from January 2003 to December 2005 at King Khalid University Hospital were identified retrospectively using the hospital computer system. Their charts were subsequently reviewed. We collected data pertaining to patients' demographics, indication of IVIG, dose regimen and physician specialty. Indications were categorized into 4 different categories: US Food and Drug Administration FDA-labeled; off-label recommended as first line; off-label recommended as alternative; and not recommended. A total of 305 patients were identified. Intravenous immunoglobulin was given to 109 (35.7%) patients for FDA-labeled indications, 29 (9.5%) patients for off-label recommended as first line indications, 97 (31.8%) for off-label recommended as alternative indications, and 70 (23%) for not r...
Intravenous immunoglobulin is the IgG plasma fraction prepared from thousands of donors. It is us... more Intravenous immunoglobulin is the IgG plasma fraction prepared from thousands of donors. It is used in the treatment of many clinical conditions. Most adverse reactions that result from its infusion are considered to be mild and self limited. We aimed to examine our local experience of immediate adverse reactions to Intravenous immunoglobulin.
Menetrier`s disease in a Saudi child
Saudi medical journal, 2013
Menetrier`s disease is a rare form of acquired gastropathy that presents mostly during adulthood,... more Menetrier`s disease is a rare form of acquired gastropathy that presents mostly during adulthood, but is extremely rare in children. It is a clinicopathological diagnosis that typically presents with abdominal pain, vomiting, and edema secondary to hypoalbuminemia. Endoscopy usually shows giant gastric mucosal folds, and gastric biopsy shows foveolar hyperplasia and decreased oxyntic glands. Here, we describe a 5-year-old boy from Saudi Arabia with typical presentation of Menetrier`s disease and serological evidence of acute cytomegalovirus infection.
A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis
A disintegrin and metalloproteinase (ADAM) 33 is a susceptibility gene associated with inflammato... more A disintegrin and metalloproteinase (ADAM) 33 is a susceptibility gene associated with inflammatory lung and skin diseases. It is selectively expressed in mesenchymal cells, and its metalloprotease activity has been linked to angiogenesis and tissue remodelling. A soluble form of ADAM33 (sADAM33) has been identified in the bronchoalveolar lavage fluid (BALF) of asthmatic patients, and its levels inversely correlate with lung function. Because of its association with inflammatory lung diseases, it was hypothesized that sADAM33 is elevated in BALF of patients with pulmonary sarcoidosis. After removal of Ig using Protein A/G and enrichment using Concanavalin A beads, sADAM33 was identified in BALF by Western blotting. A fluorescence resonance energy transfer peptide cleavage assay was used to assess ADAM33-like activity in BALF. sADAM33 protein in BALF was detected as a 25 kDa fragment, and levels were significantly increased in samples from sarcoid patients when compared to healthy controls (P < 0.05). Levels of sADAM33 were inversely correlated with lung function (FVC%) (P < 0.05) and DL(CO) % predicted (P < 0.01). No difference in sADAM33 enzymatic activity was observed between healthy and sarcoid BALF samples. Release of sADAM33 is increased in sarcoid and may be associated with abnormal lung function. sADAM33 may be a biomarker of lung tissue inflammation and remodelling in sarcoid.
A Novel Homozygous Mutation in G6PC3 Presenting as Cyclic Neutropenia and Severe Congenital Neutropenia in the Same Family
Journal of Clinical Immunology, 2013
Budesonide Nebulization Added to Systemic Prednisolone in The Treatment of Acute Asthma in Children: Double-Blind, Randomized, Controlled Trial
Chest, Jan 2, 2014
Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, hav... more Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, have also been suggested as a therapy for acute asthma when given at high doses. A double-blind, randomized, placebo-controlled trial was conducted in children aged 2 to 12 years with moderate or severe acute asthma, as determined based on a clinical score of 5 to 15 points, where 15 is the most severe. We compared the addition of budesonide 1,500 μg vs placebo to standard acute asthma treatment, which included salbutamol, ipratropium bromide, and a single dose of prednisolone 2 mg/kg given at the beginning of therapy. The primary outcome was hospital admission rate within 4 h. A total of 906 ED visits by children with moderate or severe acute asthma were evaluated. Seventy-five cases out of 458 (16.4%) in the budesonide group vs 82 of 448 (18.3%) in the placebo group were admitted (OR, 0.84; 95% CI, 0.58-1.23; P=.38). However, among cases with high baseline clinical score (≥13), significantly fewer children were admitted in the budesonide group (27 of 76 [35.5%]) than in the placebo group (39 of 73 [53.4%]; OR, 0.42; 95% CI, 0.19-0.94; P=.03). The addition of budesonide nebulization did not decrease the admission rate of children with acute asthma overall. However, it may decrease the admission rate of children with severe acute asthma. ClinicalTrials.gov; No.: NCT01524198; URL: www.clinicaltrials.gov
Annals of thoracic medicine, 2014
Asthma is a prevalent chronic disease of the respiratory system and acute asthma exacerbations ar... more Asthma is a prevalent chronic disease of the respiratory system and acute asthma exacerbations are among the most common causes of presentation to the emergency department (ED) and admission to hospital particularly in children. Bronchial airways inflammation is the most prominent pathological feature of asthma. Inhaled corticosteroids (ICS), through their anti-inflammatory effects have been the mainstay of treatment of asthma for many years. Systemic and ICS are also used in the treatment of acute asthma exacerbations. Several international asthma management guidelines recommend the use of systemic corticosteroids in the management of moderate to severe acute asthma early upon presentation to the ED. On the other hand, ICS use in the management acute asthma has been studied in different contexts with encouraging results in some and negative in others. This review sheds some light on the role of systemic and ICS in the management of acute asthma and discusses the current evidence be...
Saudi Pharmaceutical Journal, 2014
True allergic reactions to local anesthetics are extremely rare and constitute less than 1% of al... more True allergic reactions to local anesthetics are extremely rare and constitute less than 1% of all reactions. In addition, many of those allergic reactions are caused by the preservative constituents of the local anesthetics. Here we report a 12 year old girl with anaphylaxis to lidocaine (an amide local anesthetic) on two occasions. The allergy was confirmed by positive skin prick test to the drug. Skin testing and challenge to another amide local anesthetic (articaine) were negative. Subsequently, its use was well tolerated in a dental procedure. Up to our knowledge, this is the first report of a patient who is allergic to lidocaine and tolerant to articaine.
The effect of sand storms on acute asthma in Riyadh, Saudi Arabia
Annals of thoracic medicine
Major sand storms are frequent in the Middle East. This study aims to investigate the role of air... more Major sand storms are frequent in the Middle East. This study aims to investigate the role of air particulate matter (PM) level in acute asthma in children in Riyadh, Saudi Arabia. An aerosol spectrometer was used to evaluate PM < 10μm in diameter (PM10) and PM < 2.5 μm in diameter (PM2.5) concentrations in the air every 30 minutes throughout February and March 2012 in Riyadh. Data on children 2-12 years of age presenting to the emergency department of a major children's hospital with acute asthma during the same period were collected including their acute asthma severity score. The median with interquartile range (IQR) levels of PM10 and PM2.5 were 454 μg/m(3) (309,864) and 108 μg/m(3) (72,192) respectively. There was no correlation between the average daily PM10 levels and the average number of children presenting with acute asthma per day (r = -0.14, P = 0.45), their daily asthma score (r = 0.014, P = 0.94), or admission rate ( r= -0.08, P = 0.65). This was also true fo...
T1 and T2 ADAM33 single nucleotide polymorphisms and the risk of childhood asthma in a Saudi Arabian population: a pilot study
Annals of Saudi medicine
Genetic association studies have demonstrated that over 100 variants in target genes (including A... more Genetic association studies have demonstrated that over 100 variants in target genes (including ADAM33) are associated with airway remodeling and hyper-responsiveness in different ethnic groups; however, this has never been evaluated in Arabic populations. The objective of this study was to determine whether ADAM33 polymorphisms that are associated with asthma in a population of asthmatic children from Saudi Arabia. A cross-sectional pilot study comparing the polymorphisms of normal subjects and asthmatic patients from Saudi Arabia over a period of 1 year. One hundred and seven Saudi asthmatic children and 87 healthy Saudi children of 3-12 years old were assessed for allelic association of ADAM33 T1 (rs2280091), T2 (rs2280090), ST+4 (rs44707) and S1 (rs3918396) SNPs to asthma. Genotyping was done by real-time PCR, multiplex ARMS and PCR-RFLP. T1 and T2 SNP genotype frequencies in asthmatic children were significantly different compared to controls (P < .05), indicating allelic as...
Inherited IL-12p40 Deficiency
Medicine, 2013
Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of m... more Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor β1 (IL-12Rβ1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular.
Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells
Journal of Clinical Investigation, 2009
Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous autosomal recess... more Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous autosomal recessive immune disorder characterized by the occurrence of uncontrolled activation of lymphocytes and macrophages infiltrating multiple organs. Disease-causing mutations in the perforin (PRF1; also known as FHL2), Munc13-4 (UNC13D; also known as FHL3), and syntaxin-11 (STX11; also known as FHL4) genes have been identified in individuals with FHL. These genes all encode proteins involved in the cytotoxic activity of lymphocytes. Here, we show that the gene encoding syntaxin-binding protein 2 (Munc18-2; official gene symbol STXBP2) is mutated in another subset of patients with FHL (designated by us as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;FHL5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;). Lymphoblasts isolated from these patients had strongly decreased STXBP2 protein expression, and NK cells exhibited impaired cytotoxic granule exocytosis, a defect that could be overcome by ectopic expression of wild-type STXBP2. Furthermore, we provide evidence that syntaxin-11 is the main partner of STXBP2 in lymphocytes, as its expression required the presence of STXBP2. Our work shows that STXBP2 deficiency causes FHL5. These data indicate that STXBP2 is required at a late step of the secretory pathway for the release of cytotoxic granules by binding syntaxin 11, another component of the intracellular membrane fusion machinery.
Journal of Allergy and Clinical Immunology, 2008
RATIONALE: The process of mast cell and basophil degranulation is rapid, but little is known of t... more RATIONALE: The process of mast cell and basophil degranulation is rapid, but little is known of the kinetics of release and clearance of granule mediators in the upper airways of patients with allergic rhinitis following allergen challenge. METHODOLOGY: Thirty one asymptomatic grass pollen-sensitive subjects (mean age 35.3 y; range 17-51) with seasonal allergic rhinitis underwent nasal challenge out-of season. Mixed grass pollen extract was administered in escalating doses until a 50% reduction in minimum nasal cross sectional area, as measured by acoustic rhinometry, was provoked. Nasal lavage was performed at 0, 0.5, 1, 2, 4, and 6 hours. Mast cell carboxypeptidase, tryptase and histamine were measured in the lavage fluid by specific ELISA and the basophil marker, basogranulin, by dot blotting. RESULTS: Carboxypeptidase reached maximal concentrations at 0.5 hours and remained elevated at least until the 6 hour time-point. Tryptase and histamine, on the other hand, reached peak levels at 0.5 hours and thereafter returned to baseline concentrations. A second rise in the histamine concentration was evident at 4 hours in the absence of a change in tryptase levels. This coincided with a slow rise in basogranulin concentration consistent with the degranulation of basophils that had migrated to the site of inflammation. CONCLUSION: Following secretion from mast cell subpopulations and from basophils that accumulate in the tissues, granule derived mediators are released and cleared from the upper airways at quite different rates. While tryptase and histamine may have a short duration of action, carboxypeptidase may act for several hours following mast cell activation. Funding: The British Council, Thrasher Research Fund, and the Wellcome Trust 585 B cell-activating Factor of the TNF Family (BAFF) and a
Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries
Medicine, 2010
Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibil... more Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infec...
Annals of Saudi Medicine, 2009
Journal of Clinical Investigation, 2011
X-linked lymphoproliferative disease with Growth Hormone deficiency
Journal of Allergy and Clinical Immunology, 2005
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Papers by Abdullah Alangari