Immunoglobulin G Deficiency Publications (4868)
Immunoglobulin G Deficiency Publications
ELISA for detection of fibrinogen antibodies were performed and IgG purified from the patient's plasma bound to fibrinogen more strongly than did control IgG, indicating the presence of a fibrinogen-specific antibody. Thrombin-mediated fibrin polymerization was severely impaired in the patient, although thrombin-induced fibrinopeptide A release was normal. Scanning electron microscopy was used to investigate the structure of fibrin clots and revealed many pores on the surface of patient's fibrin clots. Since MELAS is often associated with autoimmune disorders, a work-up for the presence of anti-fibrinogen antibody is necessary when bleeding tendency occurs in MELAS patients along with prolonged thrombin time.
IgG for replacement is most often administered via the intravenous IgG (IVIG) or subcutaneous IgG (SCIG) routes. IVIG is usually administered every 34 weeks, and SCIG is usually administered weekly, although variations may be considered in all cases. Recently, a new product became available that uses hyaluronidase to facilitate absorption of large doses of SCIG less frequently (every 34 weeks, as with IVIG). There are important differences between the pharmacokinetics of these three routes of administration. IVIG therapy leads to high peaks and low troughs between infusions. IgG concentration fluctuates much less over time with SCIG. Hyaluronidase-facilitated SCIG is intermediate. SCIG may have lower bioavailability in comparison with IVIG and may require higher doses over time; this is not true for hyaluronidase SCIG. However, there are large variations in IgG half-life among individuals and with different products. Therefore, individualization of therapy is essential. Mild systemic flu-like adverse effects may affect up to 2025% of patients who receive IVIG, smaller fractions may experience more-severe symptoms, whereas anaphylaxis is exceedingly rare. General flu-like systemic adverse effects are minimal with SCIG (intermediate with hyaluronidase SCIG), but transient (24 hours), mild, local inflammatory symptoms at infusion sites are relatively common with both forms. Additional rare but important complications of IgG therapy include thrombotic events and hemolysis that can be seen at high doses with any route of administration. Renal adverse effects may occur with IVIG as well. The variety of IgG products and routes of administration available today creates many opportunities for physicians to work with patients to find the optimal therapy for all.
Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status. We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well. These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies for ERT for IOPD, e.g. modifying the enzyme to enhance uptake into skeletal muscle and/or to cross the blood brain barrier (BBB), will be required.
In this study, we aimed to develop a pentavalent-IRVV using the most circulating RV strains in Egypt and evaluate it against the commercially available Rotarix(®) vaccine. Trial-IRVV was developed with 5% sucrose, 2% polysorbate-80, and adsorbed on Alum to potentiate the vaccine immune response. Then, it was injected subcutaneously into mice groups at 0-, 21-, and 35-time intervals. In parallel, Rotarix was administered twice on 0 and 28(th) day. The success of the pentavalent-IRVV/monovalent-Rotarix vaccine immunity rested on achieving immunoglobulin G (IgG) exceeding 1:6,400 that implies less susceptibility to RV infection (RVI). IRVV stimulating IgG >1:6,400 could be an alternative vaccination approach to reach a reasonable protective immunization level against RVI. In addition, Alum adjuvant incorporation effectively provoked a triple elevation of the immunization pattern.
However, few studies have analyzed the titers of antibodies against HAV or HBV in IVIG products. In this study, the titers of anti-HAV and anti-HBs antibodies were measured in nineteen lots of IVIG products from five manufacturers from three countries (A, B from Korea; C, D from Japan; and E from the USA), and trough titers in plasma were estimated. Concentrations of anti-HAV antibody ranged from 1,888-8,927 mIU/mL and estimated trough titers exceeded the minimal protective value in all evaluated IVIG products. Concentrations of anti-HBs antibody ranged from 438-965 mIU/mL in products A and B and were 157, 123, and 1,945 mIU/mL in products C, D, and E, respectively. Estimated trough titers in products A, B, and E exceeded the minimal protective value but those in products C and D did not reach this threshold. These data demonstrated that available IVIG products generally provide sufficient antibodies against HAV and HBV to protect patients with PAD, although the trough concentrations of anti-HBs antibody in two IVIG products did not reach the minimum protective value.
Sixteen lots of IVIG products prepared by two Korean manufacturers (Products A and B) were evaluated. The functional antibodies were measured by serum bactericidal assay for Hib and four meningococcal serogroups and by multiplexed opsonophagocytic assay for 26 pneumococcal serotypes. The estimated trough levels of antibodies against Hib, pneumococcus, and meningococcus were calculated to determine whether the usual IVIG dose is appropriate for protecting patients with PAD.
The functional antibody levels for Hib were similar in all of the IVIG products. In contrast, serum bacterial indices of meningococcal serogroups A and Y showed significant differences between products A and B. Opsonic indices to pneumococci varied depending on the serotype in each IVIG product. The estimated trough levels of antibodies against Hib, pneumococcus, and meningococcus exceeded the protective levels in most of the IVIG products except for the antibodies against two pneumococcal serotypes.
Most of the tested commercial IVIG products had sufficient functional antibodies against Hib, pneumococcus, and meningococcus to protect patients with PAD receiving IVIG treatment. Regular and continuous evaluation of IVIG products is necessary to maintain an optimal therapeutic effect.
Altogether 21,780 infusions of Octagam in 2,397 patients were included in our analysis. The most frequent indication for Octagam was secondary immunodeficiencies (SID; n = 1,368, 11,348 infusions), followed by primary immunodeficiencies (PID; n = 363; 3,923 infusions). During the individual patient observation, 83% of SID and 67% of PID patients were free of any infection. In up to 85% of all investigator assessments, Octagam was rated to have a favorable effect. In autoimmune diseases, investigators assessed Octagam as being beneficial in 70% (immune thrombocytopenia) up to 100% (Guillain-Barré syndrome), depending on the indication. The majority of patients (92%) tolerated Octagam treatment without any ADR. The overall incidence of reported ADRs was 1.0% for all infusions. The majority of ADRs were considered non-serious (93%) and mild or moderate (87%) in severity. No unexpected ADR signal was detected.
This analysis demonstrates that the changes in the preparation of raw material used to manufacture Octagam did not affect the safety profile of Octagam® 5% and 10%. *At the time of study realization.
In a cross-sectional study, 35 adults with isolated growth hormone deficiency due to a homozygous mutation in the growth hormone releasing hormone receptor gene and 31 controls were submitted to a clinical questionnaire, physical examination serology for tripanosomiasis, leishmaniasis, HIV, tetanus, hepatitis B and C, and serum total immunoglobulin G, M, E and A measurement. The immune response was evaluated in a subset of these subjects by skin tests and response to vaccination for hepatitis B, tetanus, and bacillus Calmette-Guérin. There was no difference between the groups in history of infectious diseases and baseline serology. Isolated growth hormone deficiency subjects had lower total IgG, but within normal range. There was no difference in the response to any of the vaccinations or in the positivity to protein Purified Derived, streptokinase or candidin. Adult untreated isolated growth hormone deficiency does not cause an increased frequency of infectious diseases, and does not alter serologic tests, but is associated with lower total IgG levels, without detectable clinical impact.
This historic cohort study was performed on IBD patients with obtained IgG/IgG1 levels. The primary outcome was defined as any IBD-related bowel resection surgery and/or hospitalization. Subgroup analyses assessed particular surgical outcomes in Crohn's disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC), and ileal pouch-anal anastomosis (IPAA). The secondary outcomes included IBD drug escalations and C. difficile or cytomegalovirus infections.
A total of 136 IBD patients had IgG/G1 levels checked and adequate follow-up, 58 (42.6 %) with normal IgG/G1 levels and 78 (57.4 %) having low levels. A total of 49 patients (62.8 %) with low immunoglobulin levels had IBD-related surgeries or hospitalizations, compared to 33 patients (56.9 %) with normal levels [odds ratio (OR) 1.28, 95 % confidence interval (CI) 0.64-2.56; p = 0.49]. Low IgG/G1 levels were associated with IBD-related surgery in CD in univariate analysis [hazard ratio (HR) 4.42, 95 % CI 1.02-19.23; p = 0.048] and in Kaplan-Meier survival curve analysis (p = 0.03), with a trend toward significance on multivariate analysis (HR 3.07, 95 % CI 0.67-14.31; p = 0.15). IBD patients with low IgG/G1 levels required more small bowel resections (12.8 vs. 1.7 %, p = 0.024) and 5-aminosalicylate initiations (28.2 vs. 13.8 %, p = 0.045).
Our study demonstrated a possible association between low IgG/G1 levels and poor outcomes in CD including surgery. Future implications include using immunoglobulin levels in IBD patients as a prognostic indicator or boosting humoral immunity as a treatment in this subset.
Prior to the frozen donor egg transfer cycle, prednisone and intravenous immunoglobulin G (IVIg) treatment was initiated and patient achieved dichorionic diamniotic twin pregnancies. During pregnancy, proportion (%) of switched memory B cells CD27+IgD- increased, while percent of total CD19+ B cells and CD27-IgD+ naive B cells were gradually decreased with a high dose IVIg treatment. She developed cervical incompetence at 20 weeks of gestation, received a Cesarean section at 32 weeks of gestation due to preterm labor, and delivered twin babies. B cell subset abnormalities may be associated with infertility, RPL and preterm labor, and further investigation is needed.