A New Intravenous Immune Globulin: Novel or Not?

OBJECTIVE: To assess the clinical use and determine the place in therapy for immune globulin intravenous (IV), human-slra, a recently approved IV immune globulin for the treatment of primary immune deficiency diseases (PIDD). DATA SOURCES: A PubMed and MEDLINE search (2010 to April 2020) was conducted for relevant articles. Data were also obtained from the package insert. STUDY SELECTION AND DATA EXTRACTION: English language publications regarding the clinical efficacy and safety of immune globulin-slra were analyzed. Publications focused on use of immune globulin products were also included. DATA SYNTHESIS: Immune globulin-slra is indicated for patients with PIDD and was specifically developed to include donor plasma with high respiratory syncytial virus (RSV) antibody titers. Efficacy was demonstrated through favorable incidence of infections and infection-related complications. Patients treated with immune globulin-slra had increases in anti-RSV neutralizing antibody titers compared with baseline. Adverse events occurred at rates similar to or less than other available immune globulin products. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes a new immune globulin product available for use in patients with PIDD. A novel approach to managing patients at risk of serious infections may be to utilize products with formulations proven to not only boost IgG levels, but also antibodies to specific pathogens. CONCLUSIONS: The choice of which immune globulin product to select for a patient or formulary is complex. Each product is unique, and differences between products should be taken into consideration, along with cost and availability.

Parameters Indicating Development of Influenza-Associated Acute Necrotizing Encephalopathy: Experiences from a Single Center.

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.

Mean platelet volume and response to the first line therapy in newly diagnosed adult immune thrombocytopenia patients: a retrospective study

Background/aim: Immune thrombocytopenia (ITP) is treated by corticosteroids and/or intravenous immune globulin as the first line treatment when necessary. Mean platelet volume (MPV) is a marker of platelet production and function. In this study, we aimed to search the relationship between the MPV and the treatment response in ITP patients and it was hypothesized that MPV can be used as a predictor of the response. Materials and methods: The 70 newly diagnosed adult primary ITP patients and 70 of healthy people were included. MPV between ITP and healthy population, MPV in the diagnosis and after the treatment between the responders and the nonresponders were compared. Results: The responders had significantly higher MPV and the nonresponders had significantly lower MPV than the healthy population (11.09 and 10.21 fL, P = 0.03; 9.38 and 10.21 fL, P = 0.001). MPV in the diagnosis was significantly higher in the responders than the nonresponders (11.09 and 9.38 fL, P = 0.005). MPV significantly changed after the treatment in the responders (11.09 to 9.32 fL, P = 0.004). Conclusion: MPV can be used as a predictor of early response to the first line treatment in newly diagnosed adult primary ITP patients.

Absence of Persistent Hepatitis E Virus Infection in Antibody-Deficient Patients Is Associated With Transfer of Antigen-Neutralizing Antibodies From Immunoglobulin Products.

Background: Persistent hepatitis E virus (HEV) infection is described in a number of immunosuppressive conditions. We aimed to determine the risk of persistent HEV infection in patients with primary or secondary antibody deficiency. Methods: Two hundred forty-five antibody-deficient patients receiving regular immunoglobulin replacement therapy were tested for HEV RNA and anti-HEV immunoglobulin G (IgG). Immunoglobulin products and plasma specimens obtained from 9 antibody-deficient patients before and after intravenous immunoglobulin (IVIG) therapy, 5 recently treated patients with persistent HEV infection, and 5 healthy patients recovered from acute HEV infection were analyzed for anti-HEV IgG and for antibody reacting with HEV antigen. Results: No antibody-deficient patient had detectable plasma HEV RNA. Anti-HEV IgG was detected in 38.8% of patients. All 10 immunoglobulin products tested contained anti-HEV capable of neutralizing HEV antigen. Plasma samples collected following IVIG infusion therapy demonstrated a higher anti-HEV IgG level and neutralizing activity, compared with samples collected before IVIG therapy. Neutralizing activity was similar to that in healthy patients with recent acute HEV infection. Conclusion: The risk of persistent HEV infection in patients with antibody deficiency appears extremely low. This may be due to passive seroprotection afforded by the ubiquitous presence of anti-HEV in immunoglobulin replacement products.

Longitudinal changes in measles antibody titers in plasma donors and minimum antibody levels of immunoglobulin products for treatment of primary immunodeficiency.

BACKGROUND: To ensure that immunoglobulin (Ig) products have adequate functional antibody, the US Food and Drug Administration (FDA) requires that Ig lots contain minimum levels of measles neutralizing antibody; the current minimum is 0.48 x US Reference Ig 176. STUDY DESIGN AND METHODS: In the first part of the study, measles antibody titers were measured in donor plasma samples collected in 2007, 2011, and 2017. In the second part, trough or steady-state serum levels of measles neutralizing antibody were measured in two studies of patients with primary immunodeficiency (PID) who were treated with intravenous (Study 1; N = 46) or subcutaneous (Study 2; N = 18) Ig replacement therapy, meeting previous requirements for lot potency (≥0.6 x US Reference Ig 176). Serum measles neutralizing antibody titers were then estimated for conditions in which the potency of the Ig replacement product was 0.48 or 0.30 x US Reference Ig 176. RESULTS: Measles antibody titers in donated plasma samples declined in donors born after 1963. In the two studies of patients with PID who were treated with intravenous or subcutaneous Ig replacement therapy, all patients exhibited trough (intravenous Ig) or steady-state (subcutaneous Ig) measles neutralizing antibody titers above 0.12 IU/mL, which has been shown to protect against clinical measles in the general population. Estimates suggest that all patients except one would have continued to meet this standard if the Ig lot potency had been 0.48 or 0.30 x US Reference Ig 176. CONCLUSION: These studies provide supporting evidence that the lot release specification can be safely lowered from 0.48 to 0.30 x US Reference Ig 176, which will accommodate declining measles neutralizing antibody levels in donor plasma.

Measles antibody trough levels after treatment with immunoglobulin products and predicted levels assuming lower measles antibody specifications.

BACKGROUND: Widespread vaccination against measles has resulted in decreasing measles antibody levels in human immune globulin (IG) products. As levels continue to decline, it needs to be determined whether the release specifications for measles antibody levels in IG products can be lowered and still provide protection against infection for patients who receive IG treatment for primary immunodeficiency disease. STUDY DESIGN AND METHODS: Trough level measles neutralizing antibodies were measured in 10 pediatric patients with primary immunodeficiency disease (ages 2-16) treated with IG administered both by intravenous and subcutaneous infusion. The results were used to model worst-case (lowest) serum measles antibody levels in two cases: 1) the current case with intravenous dosage at 300 mg/kg at a measles antibody level of 0.48× Center for Biologics Evaluation and Research Reference 176 and 2) a future case with intravenous dosage at 400 mg/kg and 0.30× Center for Biologics Evaluation and Research Reference 176. RESULTS: Serum trough measles neutralizing antibody levels were an average of 11-fold or greater above minimum protective levels for immunocompetent individuals of 0.12 IU/mL in both the intravenous and subcutaneous phases of the study. Modeling using both the current worst-case dose and future case shows average levels for IG intravenous/subcutaneous infusion of 3.9/4.8- and 3.2/4.0-fold above 0.12 IU/mL for the two cases, respectively. CONCLUSION: Lowering the measles antibody level specification to 0.30× Center for Biologics Evaluation and Research Reference 176 in IG products will still provide trough serum antibody levels against measles infection of greater than 0.12 IU/mL when dosed at 400 mg/kg or higher.

HPLC fingerprinting approach for raw material assessment and unit operation tracking for IVIG production from Cohn I+II+III fraction.

The plasma-derived IgG used either for diagnostic purpose or intravenous application (in form of IVIG) in various medical therapies is certainly gaining more and more attention on annual basis. Different manufacturing processes are used to isolate immunoglobulins from human plasma. However, a quest for alternative paths in IgG isolation not only requires development of the most efficient isolation process, but also a rapid and reliable analytics to track the purification. Fast and reliable fingerprint-based method for characterization of IgG prepared from Cohn I+II+III paste is presented in this paper. The fingerprint method bases on partial separation of proteins in linear gradient on CIMac™ quaternary amine, strong anion exchange group (QA) 0.1 mL column. Partial separation of proteins does not allow simple quantitative analysis of the samples during the IgG isolation from Cohn I+II+III fraction paste, but very accurate qualitative information about the composition of the sample can be obtained in less than 5 min. From the differences in the chromatograms of various samples, the ratio between IgG and impurities in each sample can be easily assessed. The method is suitable for input material control, in-line monitoring of the downstream processing, final control of the products, as well as in stability studies and enables taking fast and accurate decisions during fractionation process.

Quantitative Evidence of Wear-Off Effect at the End of the Intravenous IgG (IVIG) Dosing Cycle in Primary Immunodeficiency.

PURPOSE: Intravenous IgG (IVIG) treatment wear-off is commonly experienced by patients, who report increased susceptibility to infection, and decreased quality of life towards the end of their 3- or 4-week dosing cycle, when serum IgG levels approach their trough. We quantified IVIG wear-off in terms of treatment efficacy and patient well-being. METHODS: Data were collected from patients enrolled in three Phase III trials of Sandoglobulin NF Liquid or Privigen, treated every 3- or 4- weeks. Pooled analyses of raw patient data compared the rate of infection and other clinical outcomes during the course of the dosing cycle. Subjective symptoms of wear-off were quantified by comparing patient-reported overall well-being scores. RESULTS: The probability of a first infection in the final week of the IVIG cycle was 1.26 (95% confidence intervals [CI]: 0.76-2.11; p = 0.3621) and 1.55 (95% CI: 1.04-2.32; p = 0.0314) times higher than in the first week, for patients on a 3-week cycle and 4-week dosing cycles, respectively. Wear-off, as manifested by a decrease in overall well-being, was experienced in 10% of all cycles and reported at least once by 61% of the patients on a 3-week cycle, and 43% of those on a 4-week cycle. CONCLUSIONS: These findings confirm the existence of decreased efficacy (treatment wear-off) towards the end of a 3-4 week IVIG dosing cycle, and provide a quantifiable evaluation to a phenomenon typically reported anecdotally. For patients experiencing wear-off, increasing the IgG dose or shortening the dosing interval and/or a switch to SCIG may be beneficial.

Optimizing IgG therapy in chronic autoimmune neuropathies: a hypothesis driven approach.

Prolonged intravenous immunoglobulin (IVIG) therapy is used for the chronic autoimmune neuropathies chronic idiopathic demyelinating polyneuropathy and multifocal motor neuropathy, but the doses and treatment intervals are usually chosen empirically due to a paucity of data from dose-response studies. Recent studies of the electrophysiology and immunology of these diseases suggest that antibody-induced reversible dysfunction of nodes of Ranvier may play a role in conduction block and disability which responds to immunotherapy more rapidly than would be expected for demyelination or axonal damage per se. Clinical reports suggest that in some cases, the effects of each dose of IVIG may be transient, wearing-off before the next dose is due. These observations lead us to hypothesize that that therapeutic IgG acts by competing with pathologic autoantibodies and that individual patients may require different IgG levels for optimal therapeutic effects. Frequent IVIG dosing and weekly subcutaneous IgG have been tried as ways of continuously maintaining high serum IgG levels, resulting in stabilization of neuromuscular function in small case series. Frequent grip strength and disability measurements, performed by the patient at home and reported electronically, can be used to assess the extent and duration of responses to IgG doses. Individualization of IgG treatment regimens may optimize efficacy, minimize disability, and identify nonresponders.

Safety monitoring of the intravenous immunoglobulin preparation Intratect® in primary and secondary immunodeficiencies: a prospective non-interventional study.

OBJECTIVES: To better characterize the risk profile of the intravenous immunoglobulin (IVIG) Intratect®, a non-interventional study was undertaken to systematically collect large-scale safety information under real-life conditions in patients with primary and secondary immunodeficiency. Secondary objectives were data on treatment modalities. METHODS: A prospective, non-interventional study was performed at 95 centers. RESULTS of an interim analysis are reported here. Intratect® (50 g/L) was administered at the physician's discretion. Data were captured from patients with different causes of immunodeficiency (61.5% with malignancy) at routine clinic visits, with a particular focus on the frequency and causality of adverse events. RESULTS: 1,313 patients were followed for a median of 294 days. At study entry, 836 patients (63.7%) were receiving therapy, most frequently IVIG treatment (37.2%). In total, 21,995 Intratect® infusions were documented (median 11 infusions per patient, median dose 200 mL). Median serum IgG level increased from 5.78 (interquartile range 3.70, 8.87) g/L at month 1 to 6.58 (4.82, 9.48) g/mL at month 12. Altogether, 689 adverse events were collected, irrespective of causality. From these, 225 (32.7%) were assessed as related to Intratect® and thus considered suspected adverse drug reactions (ADRs). Thus, the ADR rate was 1.0% per infusion. Seven ADRs (7/225, 3.1%) were graded serious. In all cases, the patients had recovered or were recovering at the time of reporting. CONCLUSIONS: Use of Intratect® for immunoglobulin substitution in primary and secondary immunodeficiency under real-life conditions is associated with a low rate of suspected ADRs. Serious ADRs are rare and manageable.

Assessment of immunoglobulin concentrates on thrombogenic activity by thrombin generation assay, prekallikrein activator assay, and size-exclusion chromatography.

BACKGROUND: Immunoglobulin G (IgG) concentrates have recently been found to be contaminated with procoagulant impurities causing thromboembolic events (TEEs) in vivo. In this study the question was raised whether a thrombin generation assay (TGA) will be able to characterize IgG samples from the Austrian market with regard to their thrombogenic potential. STUDY DESIGN AND METHODS: A total of 44 IgG concentrates have been assayed by TGA employing pooled normal plasma and Factor (F)XI-deficient plasma (FXIdp). Furthermore, the prekallikrein activator assay including determination of blank values, size-exclusion chromatography, and further test systems required for batch release testing of IgG concentrates according to the European Pharmacopeia (Pharm. Eur.) were carried out. RESULTS: All samples complied with acceptance criteria stated in the Plarm. Eur. and/or prescribed by the marketing approval. One intravenous immunoglobulin (IVIG) involved in TEEs exceeded a threshold level of 350 nmol peak thrombin, which was not exceeded after change of manufacture and by all the other IVIGs tested. Two hyperimmune globulins revealed elevated peak thrombin levels of up to 810 nmol in FXI and up to 285 nmol in FXIdp. CONCLUSION: The study indicates that the TGA is able to reliably predict procoagulant activities probably associated with the presence of FXIa and potential thrombogenicity. Comparison of thrombin generation with product-specific acceptance criteria as well as variables from other test systems as amidolytic activity and molecular size can help to monitor IgG quality and manufacturing changes with regard to thrombogenicity.

Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease.

OBJECTIVE: To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs). METHODS: Serum Th1 and Th2 cytokines, including interferon-γ (IFNγ), tumor necrosis factor α (TNFα), interleukin-10 (IL-10), IL-6, IL-4, and IL-2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre-IVIG, at 3 days after temperature normalization following IVIG treatment [post-IVIG], and 1 month posttreatment). RESULTS: Levels of IL-6, IL-10, TNFα, and IFNγ were significantly increased in KD patients pre-IVIG. Post-IVIG, the levels of IL-6, IL-10, and IFNγ quickly decreased. The levels of TNFα decreased significantly after IVIG treatment in KD patients without CALs post-IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post-IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL-4, IL-6, IL-10, and IFNγ were significantly higher in KD patients with CALs than in those without CALs. The post-IVIG levels of IL-6 and IL-10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre-IVIG, an IL-10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNFα level <2 pg/ml had a sensitivity of 66.7% and a specificity of 74.2% for predicting IVIG resistance. Post-IVIG, an IL-6 level >10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL-10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs. CONCLUSION: Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

Effect of anthrax immune globulin on response to BioThrax (anthrax vaccine adsorbed) in New Zealand white rabbits.

Development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a component of anthrax toxins. We evaluated the interaction between AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits. While pharmacokinetics of AIGIV were not altered by vaccination, the vaccine-induced immune response was abrogated in AIGIV-treated animals.

Neutralization of five subgenotypes of Enterovirus 71 by Taiwanese human plasma and Taiwanese plasma derived intravenous immunoglobulin.

Enterovirus 71 (EV71) commonly occurs in children, causing hand, foot and mouth disease (HFMD) in about 29% of patients. Studies have suggested that patients develop meningitis and encephalopathy with a mortality rate of 4-26%. EV71 subgenotypes including B4, B5, C2, C4 and C5 have caused HFMD epidemics in Taiwan. In terms of therapeutical strategy, intravenous immunoglobulin (IVIG) has been shown to improve patient conditions. In this study, the EV71 neutralizing titer was evaluated in 75 human plasmas and 8 lots of Taiwanese plasma derived IVIG. Results showed that human plasmas and IVIG significantly neutralized B4 and C2 subgenotypes. Four percent of human plasma contained neutralizing antibody titer of 1:128 against B4 and C2. Most IVIG lots possessed a median effective dose of over 100 against B4 and C2. IVIG lots had an average neutralizing capacity of 5.60, 0.90, 4.30, 1.12 and 0.77 log10 CCID50/ml against B4, B5, C2, C4 and C5, respectively. In conclusion, effective neutralization of B4 and C2 could be due to their earlier appearance in the EV71 epidemiology timeline of Taiwan. IVIG derived from Taiwanese plasma may be desirable for treatment of patients infected with EV71 of specific subgenotypes.

Retrospective analysis of weekly intravenous immunoglobulin prophylaxis versus intravenous immunoglobulin by IgG level monitoring in hematopoietic stem cell transplant recipients.

Patients undergoing allogeneic hematopoietic stem cell transplant (allo HCT) have a higher incidence of infections partly due to secondary hypogammaglobulinemia. We evaluated the role of IVIG in allo HCT patients who received prophylactic IVIG 200 mg/kg once weekly regardless of IgG level (Group 1, n = 115) compared with patients who received IVIG based on IgG level <400 mg/dL (Group 2, n = 114). Primary endpoints were the utilization of IVIG, incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), and documented infections within the first 100 days after allo HCT. Patients in both groups were similar except for a higher number of matched unrelated donor (MUD) transplants in Group 2 (62 vs. 41, P = 0.01). There were no significant differences in the incidence all grades of GVHD (55 vs. 50), VOD (2 vs. 0) or infections in the two groups except for a higher incidence of para-influenza infections in group 1 (9 vs. 0, P = 0.003) coinciding with the flu season. We recommend monthly monitoring of IgG level and replacement only if IgG level is <400 mg/dL.

Efficacy and safety of Hizentra(®) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy.

A prospective, open-label, multicenter, single-arm, Phase III study evaluated the efficacy and safety of Hizentra(®), a 20% human IgG for subcutaneous administration, in 51 primary immunodeficiency patients over 40 weeks. Patients previously on intravenous or subcutaneous IgG were switched to weekly subcutaneous infusions of Hizentra(®) at doses equivalent to their previous treatment. IgG levels achieved with Hizentra(®) were similar to pre-study levels with subcutaneous, and higher by 17.7% than pre-study levels with intravenous IgG. No serious bacterial infections were reported in the efficacy period. The rate of all infections was 5.18/year/patient, the rates of days missed from work/school, and days spent in hospital were 8.00/year/patient and 3.48/year/patient, respectively. Local reactions (rate 0.060/infusion) were mostly mild (87.3%). No serious, Hizentra(®)-related adverse events were reported. Individual median infusion durations ranged between 1.14 and 1.27 h. Hizentra(®) maintained or improved serum IgG levels without dose increases and effectively protected patients against infections.

The effect of IgG levels on the number of natural killer cells and their Fc receptors in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: High-dose intravenous immunoglobulin (IVIg) is an established treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although Fc receptors on natural killer cells have been suggested as a target for IVIg, the pharmacological effects are not yet clarified. We hypothesize that IVIg therapy, dependent on the plasma IgG level, suppresses the cytotoxic capacity by a reduction in numbers of NK cells and their Fc receptor CD16. PATIENTS AND METHODS: Ten consecutive patients with CIDP in maintenance therapy with IVIg were studied before and immediately after the infusion of 0.7-2.0 g/kg IVIg. Peripheral blood mononuclear cell samples from these patients were analyzed immediately after isolation using flow cytometry and cytotoxicity assays. RESULTS: We found that following IVIg treatment, the cytotoxic activity of NK cells in CIDP patients was suppressed, partly caused by a dose-dependent decline in the number of circulating NK cells. In addition, a dose-dependent blockage of CD16 occurred. CONCLUSIONS: The study implies that IVIg infusion induces a substantial decline in the number of peripheral NK cells and a suppression of NK-cell-mediated cytotoxicity. We propose that these impairments of the NK cells contribute to the therapeutic effect of IVIg in CIDP.

Characteristics and serology of pregnant women with cytomegalovirus immunoglobulin G seroconversion during pregnancy in Japan.

OBJECTIVE: Investigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection. MATERIALS AND METHODS: We retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection. RESULTS: Twenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p < 0.001). Titers of CMV IgM at IgG seroconversion were higher in women without (median 8.66) than with (median 6.54) congenital infection (p = 0.045). The congenital infection rate was high when IgM titers at IgG seroconversion were low (47.1% with 4.00-12.00 titers and 100% with 1.21-3.99 IgM titers) (p = 0.048). CONCLUSIONS: Nulliparous pregnant teenagers have a high risk of CMV IgG seroconversion and the CMV IgM titer at IgG seroconversion may help predict the occurrence of fetal congenital CMV infection.

Association of FcRn expression with lung abnormalities and IVIG catabolism in patients with common variable immunodeficiency.

The neonatal Fc receptor (FcRn) acts as a key regulator of IgG homeostasis and is an important sensor of luminal infection. We analyzed the influence of FcRn expression on disease phenotype and the catabolism of therapeutically administered intravenous immunoglobulins (IVIG) in 28 patients with common variable immunodeficiency (CVID). Patients with generalized bronchiectasis and fibrosis had lower levels of FCRN mRNA compared to patients without these complications (P=0.027 and P=0.041, respectively). Moreover, FCRN mRNA levels correlated negatively with the extent of bronchiectasis and the rate of IgG decline after infusion of IVIG (P=0.027 and P=0.045, respectively). No relationship of FCRN expression with age at disease onset, age at diagnosis, diagnostic delay, IgG levels or frequency of infections before or during replacement immunoglobulin treatment, the presence of lung functional abnormalities, chronic diarrhea, granulomas, lymphadenopathy, splenomegaly or autoimmune phenomena was observed. Our results showed that FcRn might play a role in the development of lung structural abnormalities and in the catabolism of IVIG in patients with CVID.