Allergy Partners of North Texas, Medical City Children's Hospital, Dallas, TX, USA.
Most primary immunodeficiency diseases (PIDDs) resulting in antibody deficiency require intravenous or subcutaneous immunoglobulin G (SCIG) replacement therapy. The flow and distribution of SCIG to the vasculature is impeded by the glycosaminoglycan hyaluronan in the extracellular matrix, which limits the infusion rate and volume per site, necessitating frequent infusions and multiple infusion sites. Hyaluronidase depolymerizes hyaluronan and is a spreading factor for injectable biologics. Read More
Background: Hard ticks are the main vectors of tick-borne encephalitis virus (TBEV). Free carnitine (FC) and acylcarnitines (AC) have the basic role in β-oxidation as well as the modulation of immune and nervous system. Homeostasis of carnitines in the TBE patients was not studied so far. Read More
Vitronectin (VN), one of the serum proteins, is known to be involved in the regulation of blood coagulation, fibrinolysis, and cell migration. It has been proposed that the regulation of fibrinolysis by VN promotes the blood-brain barrier (BBB) recovery from brain injuries such as traumatic injury and subarachnoid hemorrhage. The effects of VN on fibrinolysis in the injured brain remain unclear, however. Read More
Background: The World Health Organization (WHO) considers early and rapid diagnosis as one of the strategies to control malaria. This study compared the performance of Quantitative Buffy Coat (QBC) test and the Plasmodium lactate dehydrogenase (pLDH) rapid diagnostic test (RDT) with microscopy as the gold standard.
Materials And Methods: The study involved children ages 0-5 years who presented with a history of fever at the University College Hospital, Ibadan, Nigeria. Read More
Background: Pulmonary dendritic cells drive lung responses to foreign antigens, including Saccharopolyspora rectivirgula, a causative agent of hypersensitivity pneumonitis. While the airway inflammatory mechanisms involved in hypersensitivity pneumonitis are well described, the mechanisms leading to the break in homeostasis and hypersensitivity pneumonitis onset are not well-described, and could involve CD103+ dendritic cells, which are found at baseline and during inflammatory responses in the lung. However, recent demonstration of the ability of CD103+ dendritic cells to induce inflammatory responses starkly contrasts with their classically described role as regulatory cells. Read More
Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study, the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n = 178). The domain specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins. Read More
Context: Deficient anterior pituitary with variable immune deficiency (DAVID) syndrome is a rare disorder in which children present with symptomatic adrenocorticotropic hormone (ACTH) deficiency preceded by hypogammaglobulinemia from B-cell dysfunction with recurrent infections, called common variable immunodeficiency (CVID). Subsequent whole exome sequencing studies have revealed germline heterozygous C-terminal mutations of NFKB2 as a cause of DAVID syndrome or of CVID without clinical hypopituitarism. However, to the best of our knowledge there have been no cases in which the endocrinopathy has presented in the absence of a prior clinical history of CVID. Read More
Background: In addition to the deleterious effect on health, there is considerable economic and psychosocial morbidity associated with primary immunodeficiency diseases (PID). Also, the cost of a late diagnosis frequently results in a heavy disease burden on the patient. The objective of this study was to collect and analyze data on patients with PID in the state of Guanajuato in Mexico, to indirectly estimate the burden of the disease. Read More
The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). Read More
A high ambient temperature is a highly relevant stressor in poultry production. Heat stress (HS) has been reported to reduce animal welfare, performance indices and increase Salmonella susceptibility. Salmonella spp. Read More
The growth factor receptor Kit is involved in hematopoietic and nonhematopoietic development. Mice bearing Kit defects lack mast cells; however, strains bearing different Kit alleles exhibit diverse phenotypes. Herein, we investigated factors underlying differential sensitivity to IgG-mediated arthritis in 2 mast cell-deficient murine lines: KitWsh/Wsh, which develops robust arthritis, and KitW/Wv, which does not. Read More
Background: Patients with primary immune deficiency (PID) often require immunoglobulin G (IgG, commonly referred to as Ig) replacement therapy to prevent infections and associated comorbidities. Ig therapy can be given either through intravenous or subcutaneous routes, and both can be done in the home setting. There is limited information available on the real-world diagnosis, management, and outcomes of this patient population, given the variable disease presentation and treatment options. Read More
Panzyga(®) is a new glycine-formulated immune globulin intravenous 10% liquid for the treatment of patients suffering from immunodeficiencies and autoimmune diseases. Panzyga(®) is a high purity, native and functional IgG product with an IgG subclass distribution equivalent to normal plasma. The levels of hemagglutinins and accompanying plasma proteins (including IgA and IgM) are low. Read More
Studies demonstrated that deficiency in 17β-estradiol (E2) in postmenopausal women influences their immune system. However, few studies have reported alterations in immunologic presentation during nonnatural menopause in young females. Here we compared the differences in immune response between young C57BL/6N mice with surgical or medical variectomy and aged C57BL/6N mice with the common feature of E2 deficiency following Con A stimulation. Read More
Patients with primary antibody deficiency (PAD) are being increasingly diagnosed in the developing world. However, care of these children continues to remain suboptimal due to financial and social constraints. Immunoglobulin (Ig) trough level is an important predicting factor for infections in children on replacement immunoglobulin therapy. Read More
Purpose: This phase 3, multicenter, open-label, randomized, two-period, crossover bioequivalence trial evaluated the safety, tolerability, and pharmacokinetics of intravenous immunoglobulins (IVIGs) Gammaplex 5% and Gammaplex 10% in 33 adults and 15 children with primary immunodeficiency diseases (PIDs).
Methods: Eligible adults received five Gammaplex 5% infusions followed by five Gammaplex 10% infusions, or vice versa, stratified by a 21- or 28-day dosing regimen. Pediatric subjects received five Gammaplex 10% infusions only. Read More
Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Read More
Iron is an essential nutrient for normal cell growth, and reprogramming of iron metabolism is essential to tumor cell survival and progression. HTLV-1-associated adult T-cell leukemia/lymphoma (ATLL) has no effective therapy and high levels of cell surface transferrin receptor 1 (TFR1) expression have been reported in ATLL by us and other groups. In this study, to develop a novel molecular-targeted therapy against TFR1 to modulate iron metabolism, we initially determined the expression pattern of several iron-related genes along with TFR1 and found that ATLL cells presented characteristic of an iron-deficiency state such as high expression of iron-regulatory protein 2 (IRP2) and low expression of its E3 ubiquitin-ligase, FBXL5. Read More
Background: The etiology of Crohn's disease (CD) is still unknown although new theories are based on defects in innate immunity. We have previously shown a decrease in γδ T cells in CD patients. Previous studies have shown a high prevalence of anti-A. Read More
Clin Immunol 2017 May 2;178:56-63. Epub 2017 Feb 2.
Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan. Electronic address:
Formation of antibodies against a therapeutic enzyme is an important complication during enzyme replacement therapy (ERT) for lysosomal storage diseases. Fabry disease (FD) is caused by a deficiency of alpha-galactosidase (GLA), which results in the accumulation of globotriaosylceramide (GL-3). We have shown immune tolerance induction (ITI) during ERT in FD model mice by using an anti-B lymphocyte stimulator (anti-BlyS) antibody (belimumab). Read More
Transfus Apher Sci 2017 Feb 30;56(1):45-49. Epub 2016 Dec 30.
Université Paris Descartes, Faculté de Médecine, Service de Médecine Interne, Centre de référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Paris, France. Electronic address:
Taking advantage of the "World Apheresis Association/Société Française d'Hémaphérèse" meeting held in Paris in April 2016, this article reviews the current knowledge on the mechanisms of action of intravenous immunoglobulins. Immunoglobulins are a plasma-derived drug, which have been initially used as a replacement therapy for patients with antibody deficiency. Since 1980 they have also been used for their anti-inflammatory and immunomodulating efficacy in auto-immune diseases. Read More
Objective: Retrospective audit of IVIG Request Forms in four Ontario tertiary care centres: to determine the case mix of new IVIG requests, to authenticate information provided, and to determine documentation of clinical efficacy.
Aims: To understand contributors to increases in IVIG utilisation and to determine whether IVIG is being used and monitored appropriately.
Introduction: Intravenous immunoglobulin (IVIG) use in Canada is high compared with other developed countries. Read More
Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. Read More
Objective: To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).
Methods: Patients with moderate-to-severe SLE (score of ≥8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Responder Index (SRI4) at week 52. Read More
1 Department of Surgery, University of Alabama at Birmingham, Birmingham, AL. 2 Department of Surgery, Indiana University, School of Medicine, Indianapolis, IN. 3 Transplant Surgery, University of Alabama at Birmingham, Birmingham, AL.
Background: Antipig antibodies are a barrier to clinical xenotransplantation. We evaluated antibody binding of waitlisted renal transplant patients to 3 glycan knockout (KO) pig cells and class I swine leukocyte antigens (SLA).
Methods: Peripheral blood mononuclear cells from SLA identical wild type (WT), α1, 3-galactosyltransferase (GGTA1) KO, GGTA1/ cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) KO, and GGTA1/ CMAH /b1,4 N-acetylgalactosaminyl transferase (B4GalNT2) KO pigs were screened for human antibody binding using flow cytometric crossmatch (FCXM). Read More
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Read More
Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. Read More
J Immunol 2017 Feb 11;198(4):1595-1605. Epub 2017 Jan 11.
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, D-30625 Hannover, Germany;
Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Read More
Intravenous immunoglobulin (IVIg) is accepted as an effective and well-tolerated treatment for primary and secondary immunodeficiencies (ID) and immune thrombocytopenia (ITP). Adverse reactions of IVIg are usually mild, comprising transient flu-like symptoms, change in blood pressure and tachycardia. However IVIg therapy can be burdensome for both patients and healthcare facilities, since the infusion may take up to 4h to administer. Read More
Vitamin B12 deficiency may be responsible of serious hematologic and neurodevelopmental abnormalities. We report the case of an infant who was hospitalized because of recurrent infections, failure to thrive, hypotonia, and weakness. He was 8 months old and had been exclusively breastfed. Read More
Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence-based guideline on immunoglobulin therapy, last published in 2006. Read More
Objective: To evaluate the effect of rituximab on pathogenic autoantibodies and total Ig levels, and to identify serious adverse events in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with continuous B cell depletion.
Methods: We conducted a retrospective analysis of 239 patients with AAV treated with rituximab-induced continuous B cell depletion. Two treatment cohorts were analyzed: an induction group (n = 52) and a maintenance group (n = 237). Read More
Primary antibody deficiencies (PAD) constitute the majority of all primary immunodeficiency diseases (PID) and immunoglobulin replacement forms the mainstay of therapy for many patients in this category. Secondary antibody deficiencies (SAD) represent a larger and expanding number of patients resulting from the use of a wide range of immunosuppressive therapies, in particular those targeting B cells, and may also result from renal or gastrointestinal immunoglobulin losses. While there are clear similarities between primary and secondary antibody deficiencies, there are also significant differences. Read More
We present a case of acquired dysfibrinogenemia caused by an autoantibody that inhibited fibrin polymerization in a patient previously diagnosed with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes). The patient showed prolonged PT, aPTT, and thrombin time. There was no factor deficiency but fibrinogen antigen and activity were decreased. Read More
Human polyclonal immunoglobulin G (IgG) for therapeutic use has been available for decades. This drug was developed for treatment of antibody deficiency (replacement therapy), although its use has expanded into many anti-inflammatory and immunomodulatory applications in recent years. This review focuses on IgG prescribing for replacement therapy. Read More
Galactose-deficient IgA1 (Gd-IgA1) and IgA-IgG complexes are known to play an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed therefore to determine the impact of immunosuppression on the serum levels of Gd-IgA1, total IgA1 and IgA-IgG complexes in IgAN patients. In a retrospective study, serum samples from IgAN patients collected before transplantation (t0) and at 3- and 6-month posttransplant (t3 & t6) were used to measure the levels of Gd-IgA1, total IgA1 and IgA-IgG complexes. Read More
In patients with primary antibody deficiencies, subcutaneous administration of IgG (SCIG) replacement is effective, safe, well-tolerated, and can be self-administered at home. A new SCIG replacement at 20% concentration (Hizentra(®)) has been developed and has replaced Vivaglobin(®) (SCIG 16%). An observational prospective multi-centric open-label study, with retrospective comparison was conducted in 15 Italian centers, in order to investigate whether and to what extent switching to Hizentra(®) would affect frequency of infusions, number of infusion sites, patients' satisfaction, and tolerability in patients previously treated with Vivaglobin(®) or intravenous immunoglobulins (IVIG). Read More
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. Read More
Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid α-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Read More
Front Cell Infect Microbiol 2016 10;6:148. Epub 2016 Nov 10.
Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical BranchGalveston, TX, USA; Sealy Center for Vaccine Development and World Health Organisation Collaborating Center for Vaccine Research, University of Texas Medical BranchGalveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical BranchGalveston, TX, USA.
We evaluated the extent of attenuation and immunogenicity of the ΔlppAB and ΔlppAB ΔmsbB mutants of Salmonella enterica serovar Typhimurium when delivered to mice by the oral route. These mutants were deleted either for the Braun lipoprotein genes (lppA and lppB) or in combination with the msbB gene, which encodes an acetyltransferase required for lipid A modification of lipopolysaccharide. Both the mutants were attenuated (100% animal survival) and triggered robust innate and adaptive immune responses. Read More
Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown. We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum hydroxide (Alum) adjuvant (MPL+Alum) in inducing immunity after immunization of CD4 knockout (CD4KO) and wild-type (WT) mice with T-dependent influenza vaccine. MPL+Alum adjuvant mediated IgG isotype-switched Abs, IgG-secreting cell responses, and protection in CD4KO mice, which were comparable to those in WT mice. Read More
There is a high demand for public immunization against Rotavirus (RV), especially in Africa. In Africa, the attenuated RV vaccination is contraindicated in patients with immune diseases and nutrition deficiency. Therefore, the inactivated RV vaccine (IRVV) could be an alternative. Read More
Objective: To investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012.
Methods: We used the 2003-2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008-2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. Read More
Allergy Partners of North Texas Research, Dallas, Texas (Ms Miars); Division of Basic and Clinical Immunology, University of California, Irvine, Irvine, California (Dr Tran); and Baxalta US Inc, now part of Shire, Knoxville, Tennessee (Ms Duff). Linda K. Miars, LVN, is affiliated with Allergy Partners of North Texas Research in Dallas, Texas. Her interests in the field of infusion therapy include patient education and management of adverse reaction to immunoglobulin G (IgG) administered subcutaneously (IGSC) and IgG administered intravenously (IGIV). Michelle Tran, DNP, FNP-C, is affiliated with the University of California, Irvine in Irvine, California. Her interests in the field of infusion therapy include the management of IGIV adverse reactions and barriers to weight loss in patients with primary immunodeficiency diseases. Kimberly Duff, BSN, RN, has been a manager of clinical education in global medical affairs for Shire for the past 5 years. She has 31 years of experience in nursing, with the last 17 in the field of immunology. She provides clinical expertise to support the development of new products and helps others understand the patient experience. Ms Miars and Dr Tran have no conflicts of interest to report. Ms Duff is an employee of Shire. Editorial support was provided by BlueMomentum, a division of Ashfield Healthcare Communication (a UDG Healthcare plc company) and was funded by Shire.
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. Read More
The worldwide seroprevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) has changed over the last two decades, indicating a declining incidence of HAV and HBV infections. Therefore, vaccinations against HAV and HBV are recommended for unimmunized people before traveling to an endemic area. Unfortunately, primary antibody deficiency (PAD) patients can only obtain humoral immunity through intravenous immunoglobulin G (IVIG) replacement and not from vaccination because of a defect in antibody production. Read More
Background: Intravenous immunoglobulin G (IVIG) replacement therapy is used to prevent invasive infections in patients with primary antibody deficiency (PAD). However, few studies have functionally evaluated specific antibodies against encapsulated bacteria that cause invasive infection in patients with PAD. In this study, functional antibodies against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococci), and Neisseria meningitidis (meningococci) in IVIG therapy were evaluated. Read More
Objective: To evaluate the tolerability and safety of Octagam® 5% and 10% across all indications, ages, and treatment regimens, using data from four non-interventional post-authorization safety studies (PASS); this analysis was performed following changes in the preparation of raw material used to manufacture Octagam.
Methods: All four studies included in- and out-patients prescribed Octagam for treatment of their medical condition. Physicians used case report forms to document baseline demographics, Octagam treatment details, and data on the efficacy of Octagam, and recorded all adverse drug reactions (ADRs) and other safety data. Read More