Experience with Subgam, a Subcutaneously Administered Human Normal Immunoglobulin (ClinicalTrials.gov--NCT02247141).

Background And Objectives: A multi-centre, non-comparative study examining the efficacy and safety of Subgam, a normal immunoglobulin (IgG) given weekly as a rapid subcutaneous infusion to patients with primary immune deficiency (PID), is reported. Also included is a summary of adverse drug reactions associated with the use of marketed Subgam in the UK.

Materials And Methods: 50 patients with stable PID on IgG therapy were enrolled: Stage 1 included three infusions with prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term Subgam therapy up to 4 years.

New insights into the chemical and isotopic composition of human-body biominerals. I: Cholesterol gallstones from England and Greece.

We have analyzed gallstones from four patients of Europe and particularly from England (including samples from a mother and a daughter) and Greece. According to the XRD, FTIR, NMR and laser micro-Raman results the studied materials correspond to typical cholesterol monohydrate (ChM). The micro-morphology of cholesterol microcrystals was investigated by means of SEM-EDS.

Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort.

Introduction: This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort.

Methods: The magnitude of association for each genotype was assessed in 1,046 RA subjects from the Yorkshire Early RA cohort and in 5,968 healthy UK controls. Additional exploratory subanalyses were undertaken in subgroups defined by autoantibody status (rheumatoid factor and anti-cyclic citrullinated peptide) or disease severity (baseline articular erosions, Health Assessment Questionnaire (HAQ) score and swollen joint count (SJC)).

The shared epitope hypothesis in rheumatoid arthritis: evaluation of alternative classification criteria in a large UK Caucasian cohort.

Objective: Many classification systems for the HLA-DRB1 allelic association with rheumatoid arthritis (RA) have been reported, but few have been validated in additional populations. We sought to evaluate 3 different DRB1 allele classification systems in a large cohort of Caucasian RA patients and control subjects in the UK.

Methods: HLA-DRB1 typing was undertaken in 1,325 Caucasian RA patients and 462 healthy Caucasian controls who were residents of the UK.

A pilot study of combination anti-cytokine and anti-lymphocyte biological therapy in rheumatoid arthritis.

Background: Immunological tolerance in humans using anti-T-cell monoclonal antibodies (mAbs) may be hampered by a pro-inflammatory microenvironment. All clinical trials of such therapies in rheumatoid arthritis (RA), however, have selected patients with active disease at baseline. Concurrent neutralization of inflammation with a TNFalpha antagonist should maximize the potential of anti-T-cell mAbs to induce tolerance in RA.

A novel TNFRSF1A splice mutation associated with increased nuclear factor kappaB (NF-kappaB) transcription factor activation in patients with tumour necrosis factor receptor associated periodic syndrome (TRAPS).

Objective: To characterise and investigate the functional consequences of a novel TNFRSF1A splice site mutation causing tumour necrosis factor receptor associated periodic syndrome (TRAPS) in a 16-year-old male patient and his mother.

Methods: Mutational DNA screening was performed in the patient and his mother. Western blotting was used to analyse protein expression levels of TNFR1.

Asthma and airways collapse in two heritable disorders of connective tissue.

Objectives: This study investigated the clinical impression that there was an increased prevalence of respiratory disorders in both the Hypermobility Syndrome (HMS)/Benign Joint Hypermobility Syndrome (BJHS) and Ehlers-Danlos Syndrome (EDS), compared with the normal population.

Methods: A questionnaire was distributed to 509 subjects (221 healthy controls, 126 HMS, 162 EDS) who documented respiratory symptoms and previously diagnosed respiratory and atopic disorders. A subgroup of 157 responders underwent full clinical and serological assessments, and 57 subjects were assessed physiologically.

Low gammaglobulin subclass 2 levels in paediatric cystic fibrosis patients followed over a 2-year period.

The aim of this study was to relate serum immunoglobulin G2 subclass levels in a large paediatric population with cystic fibrosis, to clinical status and antibody levels to Haemophilus influenzae type b and Streptococcus pneumoniae and to observe any changes over a 2-year period. IgG subclasses were measured in 131 patients. Results were compared with levels from age-related normal population data.

The measurement of whole blood pre-treatment cyclosporine A: metabolite ratios predicts the onset of renal dysfunction in recipients of allogeneic stem cell transplantation.

Background: In the context of post-transplant immunosuppression, cyclosporine A (CSA) is dose adjusted in accordance with whole blood drug monitoring. While currently available immunoassay systems primarily target the parent drug, cross-reactivity results in the detection of the major circulating CSA metabolites, though their contribution to both immunosuppression and toxicity remain unclear. This study examines the relationship of CSA metabolites to hepatic and renal dysfunction and the incidence of graft-versus-host disease (GvHD) through parallel assaying of parent drug and drug/metabolites expressed as a metabolite ratio (Cp:mR).

Immunoglobulin and IgG subclass levels in a regional pediatric cystic fibrosis clinic.

The aim of this study was to report serum immunoglobulin (Ig) and IgG subclass levels in a large pediatric population with cystic fibrosis, and relate these to measures of disease severity. Total immunoglobulin levels were measured in 154 patients, and IgG subclass levels were measured in 136 patients and compared to age-related normal population data and to levels reported in previously published studies of children with cystic fibrosis. Clinical data were also collected: genotype; height, weight, and BMI standard deviation scores; FEV(1) (as percent predicted); Shwachmann-Kulczycki (S-K) and Northern chest X-ray scores; and Pseudomonas aeruginosa infection status.

Influence of recipient and donor IL-1alpha, IL-4, and TNFalpha genotypes on the incidence of acute renal allograft rejection.

Aims: To determine whether polymorphisms of the genes encoding donor or recipient interleukin 1alpha (IL-1alpha), tumour necrosis factor alpha (TNFalpha), or IL-4 have any impact on the incidence of acute rejection after renal transplantation.

Methods: All donors and recipients were genotyped for three polymorphisms in the three cytokine genes: IL1A -889, TNFA -308, and IL4 -590.

Results: Statistical analysis of the data obtained revealed no association between the cytokine gene polymorphisms tested and the incidence of post-transplant acute rejection.

Intravenous immunoglobulin-induced panel reactive antibody A reduction: not all preparations are created equal.

Background: Use of intravenous (IV) immunoglobulin (Ig) to obtain panel reactive antibody (PRA) A reduction in sensitized patients has been widely reported. Because no IVIg preparation is formulated specifically for this purpose, the authors have sought to determine whether, through laboratory testing, they could guide the rational choice of product for clinical use.

Methods: Using a flow cytometric approach, the authors have quantitatively determined the capacity of 22 different IVIg preparations to cause PRA reduction.

Does the shared epitope genotype influence either the susceptibility to or the phenotype of corneal melting?

Purpose: To investigate the role of the shared epitope alleles in determining susceptibility to and the phenotype of corneal melting in patients with rheumatoid arthritis (RA).

Methods: The HLA class 1 and 2 genotype was determined for 17 patients with rheumatoid-associated comeal melting by the phototyping method. HLA-DR4 subtyping was performed by PCR sequence-based typing.

The carriage of pro-inflammatory cytokine gene polymorphisms in recurrent pregnancy loss.

Problem: Recurrent pregnancy loss (RPL) affects 2-4% of couples, and remains largely unexplained. Recent studies have examined the role of cytokines in the maintenance of normal pregnancy, which is linked with an increased expression of Th2 cytokines. Overexpression of Th1 cytokines is associated with RPL.

Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups.

Objective: To investigate a possible association between a functional polymorphism in the intermediate-affinity receptor for IgG called Fc-gamma receptor type IIIA (FcgammaRIIIA [CD16]) and rheumatoid arthritis (RA).

Methods: This was an allelic association study in which a single nucleotide polymorphism in FcgammaRIIIA was examined as a susceptibility and/or severity factor for RA. The FcgammaRIIIA-158V/F polymorphism was genotyped by direct sequencing in 2 well-characterized ethnic groups, UK Caucasians (141 RA patients and 124 controls) and North Indians and Pakistanis (108 RA patients and 113 controls).

Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis.

The major cause of mortality in patients with cystic fibrosis (CF) is lung disease. Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene product in the airways is a potential treatment. Clinical studies in which the CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in modest, transient gene expression.

No strong association between alleles of tumour necrosis factor alpha and interleukin-1 receptor antagonist and corneal melting associated with systemic vasculitis.

Aims: To investigate polymorphism within the tumour necrosis factor alpha (TNF-alpha) promoter region and within the interleukin-1 receptor antagonist (IL-1Ra) gene in a group of patients with vasculitis associated corneal melting.

Methods: The polymorphic regions at position -308 on the TNF-alpha promoter region and in intron 2 of the IL-1Ra gene were amplified by the polymerase chain reaction (PCR). The resultant products were separated by electrophoresis on agarose gels and visualised by ethidium bromide staining.

The effect of sulphasalazine on neutrophil superoxide generation in rheumatoid arthritis.

The production of superoxide by the peripheral blood neutrophils of 19 patients with active rheumatoid arthritis was measured during treatment with sulphasalazine (SASP). The response to drug treatment was determined by change in plasma viscosity, CRP, early morning stiffness and articular index over a 10-point scale. Of the 19 patients studied, eight were considered to have responded well to SASP and seven to have responded poorly or not at all.

An assessment of the comparative utility of functional and molecular level analyses in the investigation of patients with thrombophilia.

Aim-To determine the relation of the low anticoagulant response phenotype with the Factor V Q506 (Leiden) mutation in a cohort of patients with thrombophilia.Methods-Fifty four patients with either a personal or family history of deep vein thrombosis were investigated both for their anticoagulant response by the activated protein C resistance test (APCR) and their genetic status in respect of the Leiden mutation by means of a PCR-RFLP method.Results-Low APCR ratios do not necessarily predict possession of the Leiden mutation.