Research

Practical Considerations for Self-Administration of Subcutaneous Immunoglobulin G Utilizing Recombinant Human Hyaluronidase, an Advanced Method of Subcutaneous Administration: A Nurse’s Perspective.

J Infus Nurs. 2016 Nov/Dec;39(6):359-368

Authors: Miars LK, Tran M, Duff K

Abstract
An approved subcutaneous infusion of immunoglobulin G using recombinant human hyaluronidase (IGHy) allows adult patients with primary immunodeficiency disease to self-administer every 3 to 4 weeks using 1 to 2 subcutaneous infusion site(s). This article reviews the practical considerations for nurses to simplify patient education and training. Key considerations include pump choice and parameters, ancillary supplies, and technique. Patient education includes infusion log upkeep and management of potential reactions. Educational initiatives should be designed to meet specific patient needs. Successful IGHy self-administration depends on proper patient training and continuing interaction between the health care team and the patient to optimize the patient experience.

PMID: 27828933 [PubMed – in process]

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A Case Report of X-Linked Hyperimmunoglobulin M Syndrome with Lipoma Arborescens of Knees.

Case Rep Med. 2016;2016:5797232

Authors: Dong Q, Zhao J, Yao Z, Liu X, He H

Abstract
The X-linked hyperimmunoglobulin M syndrome (HIGM), caused by mutations in the CD40LG gene, is a kind of primary immunodeficiency disease (PID). Patients with X-linked HIGM are susceptible to infection as well as autoimmune diseases. Lipoma arborescens (LA) is a rare benign tumor, of which the pathogenesis mechanism has not been clearly understood. We report a case of HIGM combined with LA in a 22-year-old male patient. A new deletion mutation of CD40LG gene was detected in this case. The possible relationship between HIGM and LA was also discussed.

PMID: 27818686 [PubMed – in process]

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Triptolide inhibits the migration and invasion of rheumatoid fibroblast-like synoviocytes by blocking the activation of the JNK MAPK pathway.

Int Immunopharmacol. 2016 Oct 27;41:8-16

Authors: Yang Y, Ye Y, Qiu Q, Xiao Y, Huang M, Shi M, Liang L, Yang X, Xu H

Abstract
Triptolide, a primary active ingredient extracted from a traditional Chinese herb, Tripterygium wilfordii Hook F, has been demonstrated to have a positive therapeutic effect on patients with rheumatoid arthritis (RA); however, its mechanism of action against RA is not well established. Therefore, in the present study, we observed the effect of triptolide on the aggressive behavior of RA fibroblast-like synoviocytes (RA FLSs), and we explored its underlying signal mechanisms. We found that triptolide treatment significantly reduced the migratory and invasive capacities of RA FLSs in vitro. We also demonstrated that the invasion of RA FLSs into the cartilage, evaluated in the severe combined immunodeficiency (SCID) mouse co-implantation model, was attenuated by treatment with triptolide in vivo. Additionally, the immunofluorescence results showed that triptolide treatment decreased the polymerization of F-actin and the activation of matrix metalloproteinase 9 (MMP-9). To gain insight into the molecular signal mechanisms, we determined the effect of triptolide on the activation of MAPK signal pathways. Our results indicate that triptolide treatment reduced the TNF-α-induced expression of phosphorylated JNK, but did not affect the expression of phosphorylated p38 and ERK. A JNK-specific inhibitor decreased the migration of RA FLSs. We also observed that triptolide administration improved clinical arthritic conditions and joint destruction in mice with collagen-induced arthritis (CIA). Thus, our findings suggest that the therapeutic effects of triptolide on RA might be, in part, due to its contribution to the aggressive behavior of RA FLSs.

PMID: 27816728 [PubMed – as supplied by publisher]

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Cutaneous and Visceral Chronic Granulomatous Disease Triggered by a Rubella Virus Vaccine Strain in Children With Primary Immunodeficiencies.

Clin Infect Dis. 2016 Oct 6;:

Authors: Neven B, Pérot P, Bruneau J, Pasquet M, Ramirez M, Diana JS, Luzi S, Corre-Catelin N, Chardot C, Moshous D, Leclerc Mercier S, Mahlaoui N, Aladjidi N, Le Bail B, Lecuit M, Bodemer C, Molina TJ, Blanche S, Eloit M

Abstract
Persistence of rubella live vaccine has been associated with chronic skin granuloma in 3 children with primary immunodeficiency. We describe 6 additional children with these findings, including 1 with visceral extension to the spleen.

PMID: 27810866 [PubMed – as supplied by publisher]

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Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing.

J Clin Immunol. 2016 Nov 2;

Authors: Engelhardt KR, Xu Y, Grainger A, Germani Batacchi MG, Swan DJ, Willet JD, Abd Hamid IJ, Agyeman P, Barge D, Bibi S, Jenkins L, Flood TJ, Abinun M, Slatter MA, Gennery AR, Cant AJ, Santibanez Koref M, Gilmour K, Hambleton S

Abstract
PURPOSE: We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions.
METHODS: Of a total of 12 undiagnosed patients with T-B+NK+ SCID, we analyzed eight probands by WES, using GATK to detect single nucleotide variants (SNVs) and small insertions and deletions (INDELs) and ExomeDepth to detect CNVs.
RESULTS: We found heterozygous single- or multi-exon deletions in IL7R, a known disease gene for autosomal recessive T-B+NK+ SCID, in four families (seven patients). In three families (five patients), these deletions coexisted with a heterozygous splice site or nonsense mutation elsewhere in the same gene, consistent with compound heterozygosity. In our cohort, about a quarter of T-B+NK+ SCID patients (26%) had such compound heterozygous IL7R deletions.
CONCLUSIONS: We show that heterozygous IL7R exon deletions are common in T-B+NK+ SCID and are detectable by WES. They should be considered if Sanger sequencing fails to detect homozygous or compound heterozygous IL7R SNVs or INDELs.

PMID: 27807805 [PubMed – as supplied by publisher]

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CD169(+) macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection.

Cell Death Dis. 2016 Nov 3;7(11):e2446

Authors: Shaabani N, Duhan V, Khairnar V, Gassa A, Ferrer-Tur R, Häussinger D, Recher M, Zelinskyy G, Liu J, Dittmer U, Trilling M, Scheu S, Hardt C, Lang PA, Honke N, Lang KS

Abstract
Upon infection with persistence-prone virus, type I interferon (IFN-I) mediates antiviral activity and also upregulates the expression of programmed death ligand 1 (PD-L1), and this upregulation can lead to CD8(+) T-cell exhaustion. How these very diverse functions are regulated remains unknown. This study, using the lymphocytic choriomeningitis virus, showed that a subset of CD169(+) macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169(+) macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus. Lack of CD169(+) macrophages also limited the IFN-I-dependent expression of PD-L1. Enhanced viral replication in the absence of PD-L1 led to persistence of virus and prevented CD8(+) T-cell exhaustion. As a consequence, mice exhibited severe immunopathology and died quickly after infection. Therefore, CD169(+) macrophages are important contributors to the IFN-I response and thereby influence antiviral activity, CD8(+) T-cell exhaustion and immunopathology.

PMID: 27809306 [PubMed – in process]

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STAT mutations as program switchers: turning primary immunodeficiencies into autoimmune diseases.

J Leukoc Biol. 2016 Nov 1;:

Authors: Lorenzini T, Dotta L, Giacomelli M, Vairo D, Badolato R

Abstract
STAT proteins are a family of transcription factors that mediate cellular response to cytokines and growth factors. Study of patients with familial susceptibility to pathogens and/or autoimmune diseases has led to the identification of 7 inherited disorders that are caused by mutations of 4 STAT family genes. Homozygous or compound heterozygous mutations of STAT1 lead to complete or partial forms of STAT1 deficiency that are associated with susceptibility to intracellular pathogens and herpetic infections. Patients with heterozygous STAT1 gain-of-function (GOF) mutations usually present with chronic mucocutaneous candidiasis (CMC) but may also experience bacterial and viral infections, autoimmune manifestations, lymphopenia, cerebral aneurysms, and increased risk to develop tumors. STAT2 deficiency has been described in 5 family members and is characterized by selective susceptibility to viral infections, whereas STAT3 loss-of-function (LOF) mutations are causative of the autosomal-dominant hyper-IgE syndrome (HIES), a condition that is characterized by cutaneous and respiratory infections in association with mucocutaneous candidiasis, eczema, skeletal and connective tissue abnormalities, eosinophilia, and high levels IgE. STAT5B LOF and STAT3 GOF mutations are both associated with disorders characterized by autoimmune or allergic manifestations, together with increased risk of infections. Particularly, STAT5b deficiency results in growth hormone (GH) insensitivity, immunodeficiency, diarrhea, and generalized eczema, whereas STAT3 GOF mutations result in autoimmune cytopenia, lymphadenopathy, short stature, infections, enteropathy, and multiorgan autoimmunity, including early-onset type I diabetes, thyroiditis, hepatitis, arthritis, and interstitial lung disease.

PMID: 27803128 [PubMed – as supplied by publisher]

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Splenic Peliosis Resulting in Spontaneous Splenic Rupture in a Concomitant Hepatic and Renal Allograft Recipient.

Exp Clin Transplant. 2016 Nov;14(Suppl 3):114-115

Authors: Börcek P, Özdemir BH, Yılmaz Akçay E, Haberal M

Abstract
Splenic peliosis is an exceedingly rare complication following liver and kidney transplant, with few previously reported cases. A 24-year-old man with chronic renal and hepatic failure due to primary oxalosis underwent concomitant renal and hepatic transplant. On the eighth day of successful transplant, he showed signs and symptoms of hypovolemia with suspicion of intra-abdominal bleeding. Diagnostic laparotomy was performed, yielding splenic rupture, and a splenectomy was performed. Macroscopically, the spleen was ruptured, and the cut surface displayed multiple parenchymal blood-filled cysts. Microscopically, the splenic microarchitecture was distorted by numerous irregular hemorrhagic lacunes partially lined by sinusoidal endothelium. Splenic peliosis was diagnosed. The patient recovered with splenectomy. Peliosis is a condition characterized by multiple bloodfilled cavities in parenchymatous organs, and it most frequently affects the liver. It is thought to be related to many conditions, including hematologic malignancies, acquired immuno deficiency syndrome, chronic alcoholism, use of oral contraceptives, and posttransplant immunodeficiency state. However, peliosis of the spleen, compared with the liver, is relatively rare, and it may cause spontaneous splenic rupture. Although rare, splenic peliosis and secondary splenic rupture is a significant posttransplant complications leading to unexplained hypovolemia.

PMID: 27805528 [PubMed – in process]

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Inborn errors of T cell immunity underlying autoimmune diseases.

Expert Rev Clin Immunol. 2016 Nov 1;

Authors: Maródi L

Abstract
Immunopathological diseases have traditionally been classified as autoimmune/inflammatory, allergic, and primary immunodeficiency (PID) conditions. Different clinical disciplines have been established along with these classifications resulting in artificial separation of immune disorders in clinical practice and the establishment of professional societies and journals focusing on these seemingly different areas of clinical medicine. Understanding better the genetics of human immunity and immunopathology has changed our approach to such a classification. Monogenic autoimmunity best exemplified by autoimmune polyendocrine syndrome type 1 (APS-1) and immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) has taught us how to re-evaluate previously existing dogmas. Discovery of various genetic errors of immunity has provided powerful insight into a better understanding of disease mechanisms and tolerance to self and non-self. We describe here a few monogenic primary T cell deficiencies as examples that PIDs may actually underlie autoimmune diseases (Table 1).

PMID: 27801603 [PubMed – as supplied by publisher]

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