Research

Specific Antibody Deficiency: Controversies in Diagnosis and Management.

Front Immunol. 2017;8:586

Authors: Perez E, Bonilla FA, Orange JS, Ballow M

Abstract
Specific antibody deficiency (SAD) is a primary immunodeficiency disease characterized by normal immunoglobulins (Igs), IgA, IgM, total IgG, and IgG subclass levels, but with recurrent infection and diminished antibody responses to polysaccharide antigens following vaccination. There is a lack of consensus regarding the diagnosis and treatment of SAD, and its clinical significance is not well understood. Here, we discuss current evidence and challenges regarding the diagnosis and treatment of SAD. SAD is normally diagnosed by determining protective titers in response to the 23-valent pneumococcal polysaccharide vaccine. However, the definition of an adequate response to immunization remains controversial, including the magnitude of response and number of pneumococcal serotypes needed to determine a normal response. Confounding these issues, anti-polysaccharide antibody responses are age- and probably serotype dependent. Therapeutic strategies and options for patients with SAD are often based on clinical experience due to the lack of focused studies and absence of a robust case definition. The mainstay of therapy for patients with SAD is antibiotic prophylaxis. However, there is no consensus regarding the frequency and severity of infections warranting antibiotic prophylaxis and no standardized regimens and no studies of efficacy. Published expert guidelines and opinions have recommended IgG therapy, which are supported by observations from retrospective studies, although definitive data are lacking. In summary, there is currently a lack of evidence regarding the efficacy of therapeutic strategies for patients with SAD. We believe that it is best to approach each patient as an individual and progress through diagnostic and therapeutic interventions together with existing practice guidelines.

PMID: 28588580 [PubMed – in process]

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Molecular Typing of Staphylococcus aureus Isolated from Patients with Autosomal Dominant Hyper IgE Syndrome.

Pathogens. 2017 Jun 06;6(2):

Authors: Sastalla I, Williams KW, Anderson ED, Myles IA, Reckhow JD, Espinoza-Moraga M, Freeman AF, Datta SK

Abstract
Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3). This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with Candida and Staphylococcus aureus. It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci. However, these alterations have not been characterized at the species- and strain-level. Since S. aureus infections are influenced by strain-specific expression of virulence factors, information on colonizing strain characteristics may provide insights into host-pathogen interactions and help guide management strategies for treatment and prophylaxis. The aim of this study was to determine whether the immunodeficiency of AD-HIES selects for unique strains of colonizing S. aureus. Using multi-locus sequence typing (MLST), protein A (spa) typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the S. aureus isolates (n = 13) found on the skin of twenty-one patients with AD-HIES. We found a low diversity of sequence types, and an abundance of strains that expressed methicillin resistance, Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxins K and Q (SEK, SEQ). Our results indicate that patients with AD-HIES may often carry antibiotic-resistant strains that harbor key virulence factors.

PMID: 28587312 [PubMed – in process]

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Granulomatous-Lymphocytic Interstitial Lung Disease in a Patient With Common Variable Immunodeficiency.

Curr Probl Diagn Radiol. 2017 Apr 14;:

Authors: Shah JL, Amin SB, Verma N, Mohammed TL

Abstract
Common variable immunodeficiency is the most common primary immunodeficiency and consists of impaired immunoglobulin production causing recurrent sinopulmonary infections. The most common cause of mortality for this disorder, however, is from the development of malignancy and autoimmune disorders. One common entity that develops is a systemic granulomatous and lymphoproliferative disorder that can cause an interstitial lung disease more formally referred to as granulomatous-lymphocytic interstitial lung disease (GL-ILD). We discuss a case of a 25-year-old woman with common variable immunodeficiency and GL-ILD and review the literature to summarize the most common radiological findings to raise the suspicion for GL-ILD on high-resolution computed tomography and delineate this from infection and other mimickers. We will also review key histopathological characteristics for diagnosis and the clinical approach and treatment options for this rare disease.

PMID: 28583689 [PubMed – as supplied by publisher]

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An Expanded Role for HLA Genes: HLA-B Encodes a microRNA that Regulates IgA and Other Immune Response Transcripts.

Front Immunol. 2017;8:583

Authors: Chitnis N, Clark PM, Kamoun M, Stolle C, Brad Johnson F, Monos DS

Abstract
We describe a novel functional role for the HLA-B locus mediated by its intron-encoded microRNA (miRNA), miR-6891-5p. We show that in vitro inhibition of miR-6891-5p impacts the expression of nearly 200 transcripts within the B-lymphoblastoid cell line (B-LCL) COX, affecting a large number of metabolic pathways, including various immune response networks. The top affected transcripts following miR-6891-5p inhibition are those encoding the heavy chain of IgA. We identified a conserved miR-6891-5p target site on the 3’UTR of both immunoglobulin heavy chain alpha 1 and 2 (IGHA1 and IGHA2) transcripts and demonstrated that this miRNA modulates the expression of IGHA1 and IGHA2. B-LCLs from IgA-deficient patients expressed significantly elevated levels of miR-6891-5p when compared with unaffected family members. Upon inhibition of miR-6891-5p, IgA mRNA expression levels were increased, and IgA secretion was restored in the B-LCL of an IgA-deficient patient. These findings indicate that miR-6891-5p regulates IGHA1 and IGHA2 gene expression at the posttranscriptional level and suggest that increase in miR-6891-5p levels may contribute to the etiology of selective IgA deficiency.

PMID: 28579988 [PubMed – in process]

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Immunomodulatory effect of G2013 (a-L-Guluronic acid) on theTLR2 and TLR4 in human mononuclear cells.

Curr Drug Discov Technol. 2017 Jun 04;:

Authors: Sharifi L, Mohsenzadegan M, Aghamohammadi A, Rezaei N, Tofighi Zavareh F, Bokaie S, Moshiri M, Azizi G, Mirshafiey A, Aghazadeh Z

Abstract
BACKGROUND: Inhibition of Toll-like receptors (TLRs) signaling have been established as a new method for development of anti-inflammatory drugs instead of NSAIDs (non-steroid anti-inflammatory drugs). Since the immunomodulatory role of G2013 was reported in some recent experiments, we decided to assess the effects of G2013 (a-L-Guluronic acid) on the protein expression of TLR2 and TLR4, their downstream signaling cascade, and the secretion of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs).
METHOD: After blood sampling from 16 healthy donors, PBMCs were isolated and treated with/without lipopolysaccharide (LPS), lipopolyteichoic acid (LTA), and G2013. Flow cytometry was done for detecting the protein expression of TLR2 and TLR4. MyD88, IkB, Tollip, and NFkB mRNA expression were assessed by real-time PCR. ELISA was performed for assessing the concentration of IL-1β and IL-6.
RESULTS: G2013 at concentration of 25 mg/mL (high dose) significantly down-regulated NF-κB, IkB and MyD88 mRNA expression and suppressed the secretion of IL-1β by PBMCs. The findings indicate that G2013 may exert its regulatory effect under normal condition via Tollip in a dose dependence pathway. Our results demonstrated that G2013 had no profound impact on the protein expression of TLR2 and TLR4.
CONCLUSION: At the conclusion, our findings point to the immunomodulatory effect of G2013 on the TLR2 and TLR4 signaling cascade and cytokine production by PBMCs. These findings could lead to establishment of new safe anti-inflammatory drugs in the future.

PMID: 28578651 [PubMed – as supplied by publisher]

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A novel germline gain-of-function variant in PIK3CD.

Clin Immunol. 2017 May 31;:

Authors: Rae W, Gao Y, Ward D, Mattocks CJ, Eren E, Williams AP

PMID: 28578023 [PubMed – as supplied by publisher]

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Seven chronic granulomatous disease cases in a single-center experience and a review of the literature.

Asian Pac J Allergy Immunol. 2017 Jun 01;:

Authors: Kutluğ Ş, Şensoy G, Birinci A, Saraymen B, Yavuz Köker M, YΙldΙran A

Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme system. This disease causes the disordered functioning of phagocytic cells. It is characterized by life-threatening and/or recurrent infections by bacteria and fungi. CGD has one X-linked recessive subtype (X-CGD) and four autosomal recessive subtypes (AR-CGD), and the differential diagnosis is important in such chronic inflammatory disorders.
OBJECTIVES: To report the clinical and laboratory characteristics of our CGD patients based on their genetic characteristics.
METHODS: Seven boys with CGD were reviewed based on clinical findings and genetic results. Dihydrorhodamine-1,2,3 (DHR) assay with flow cytometry was used as a diagnostic test. Genetic analysis was conducted to establish definitive diagnoses in all patients with CGD.
RESULTS: The age of diagnosis varied between 1.5 years and 15 years. The most frequent clinical presentation was pneumonia, and two patients had BCG-itis. Four patients had the AR-CGD phenotype, and three patients had the X-CGD phenotype. Severe invasive infections due to Aspergillus, Staphylococcus, and Serratia species were reported. Frequent lung and lymph node involvement was observed during follow-up of the cases.
CONCLUSIONS: CGD is life-threatening disease that involves deep-seated infection. In our patients, the most commonly affected organs were the lungs and lymph nodes. Phagocytic disorders should be considered in cases of recurrent infectious diseases, invasive fungal diseases, BCG complications that are not self-limiting, unexplained lymphadenitis or osteomyelitis, and chronic inflammatory disorders.

PMID: 28577521 [PubMed – as supplied by publisher]

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Differential diagnosis in ulcerative colitis in an adolescent: Chronic granulomatous disease needs extra attention.

World J Gastrointest Pathophysiol. 2017 May 15;8(2):87-92

Authors: Kotlarz D, Egritas Gurkan O, Haskologlu ZS, Ekinci O, Aksu Unlusoy A, Gürcan Kaya N, Puchalka J, Klein C, Dalgic B

Abstract
Chronic granulomatous disease (CGD) is a primary immune deficiency that is commonly diagnosed under the age of 5 years (95%) and is rarely seen in adulthood. CGD may manifest as inflammatory bowel disease (IBD) in childhood. Without proper diagnosis, these patients may be monitored for years as IBD; some may even be regarded as steroid-resistant ulcerative colitis (UC) and end up having a colectomy. In this case report, we described a patient who had been followed-up for years as UC and subsequently underwent colectomy, but was finally diagnosed in adulthood as primary immune deficiency.

PMID: 28573071 [PubMed – in process]

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Identification of Novel JAK3 Mutations by Whole-Exome Sequencing in a Korean Boy With Severe Combined Immunodeficiency.

J Investig Allergol Clin Immunol. 2017 Jun;27(3):187-189

Authors: Shim YJ, Ha JS

PMID: 28570225 [PubMed – in process]

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Associating liver partition and portal vein ligation for staged hepatectomy: A surgical technique for liver resections.

J Res Med Sci. 2017;22:52

Authors: Sanei B, Sheikhbahaei S, Sanei MH, Bahreini A, Jafari HR

Abstract
BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel surgical technique liver resection in traditionally nonresectable primary intrahepatic tumors or colorectal liver metastases.
MATERIALS AND METHODS: From June 2013 to March 2014, patients with primary tumor of liver or colorectal tumors with liver metastasis were selected to evaluate whether they met the initial criteria for ALPPS procedure.
RESULTS: Nine patients enrolled in the study with primary diagnoses of colon and rectosigmoid cancer, carcinoid tumor, gastrointestinal stromal tumor of small intestine, hepatocellular carcinoma, and pancreatic neuroendocrine tumor (PNET). Four candidates excluded from the study prior or during the first step operation due to fatty liver, hepatic fibrosis, peritoneal seeding, and multiple small intestine metastases. Five patients underwent two stages of ALPPS with the interval of about 1 week. Liver hypertrophy was 100% among our candidates after the initial step. One postoperative death happened because of massive pulmonary thromboembolism Recurrence of liver metastasis was seen in one patient. Hepatic failure Class B and A were observed in two patients which did not progress during follow-up period. One patient developed an enterocutaneous fistula.
DISCUSSION: We recommend to use 2 organ bags, one for wrapping right lobe and the other one for covering visceral organs and also do liver biopsy in suspicious cases of damaged liver parenchyma and laparoscopic exploration of abdomen for seeding and multiple metastases prior to laparotomy.
CONCLUSION: As the procedure has not been well established and verified by oncologists yet, further studies are required to define the exact indications of ALPPS.

PMID: 28567071 [PubMed – in process]

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