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Objective: To clarify the impact of intravenous infusion of gamma globulin (IVIg) on antinuclear antibodies (ANAs) in children., Methods: A retrospective analysis was performed on the data of children with nonspecific autoantibody-related diseases whose antinuclear antibody (ANA) and autoantibody profiles were detected in our hospital from January to March 2022. A total of 108 patients with a clear history of IVIg infusion within 28 days composed the IVIg group, and 1201 patients without a history of IVIg infusion composed the non-IVIg group., Results: All patients in the IVIg group had either positive ANAs or positive autoantibodies. Anti-SSA, anti-Ro52 and anti-AMA Mi2 were the top three autoantibodies in the IVIg group. The proportions of patients who were positive for either of these three autoantibodies in the IVIg group were significantly greater than those in the non-IVIg group (all P<0.5). Spearman correlation analysis revealed that the signal intensities of anti-SSA and anti-Ro52 were negatively correlated with the number of days of ANA detection after IVIg infusion (P<0.05). Multiple logistic analyses revealed that a greater total dosage of IVIg, greater IVIg per kilogram of body weight, and fewer ANA detection days after IVIg infusion were independent risk factors for positive anti-SSA and anti-Ro52 results., Conclusions: It is recommended that if rheumatic diseases are suspected, ANA detection should be carried out beforeIVIg infusion. But for patients who are positive for at least one of these three autoantibodies after IVIg infusion, doctors should first consider adoptive antibodies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Zhou, Zhang, Wang, Yan, Wang, Tang and Luo.)

Rationale: Viruses are the most common pathogens that can cause infection-related non-recurrent death after transplantation, occurring mostly from the early stages of hematopoietic stem cell transplantation (HSCT) to within 1 year after transplantation. Human coronavirus (HCoV)-NL63 is a coronavirus that could cause mortality among patients with underlying disease complications. Serological tests are of limited diagnostic value in immunocompromised hosts and cases of latent infection reactivation. In contrast, macro-genomic high-throughput (DNA and RNA) sequencing allows for rapid and accurate diagnosis of infecting pathogens for targeted treatment., Patient Concerns: In this report, we describe a patient who exhibited acute B-lymphocytic leukemia and developed complicated pulmonary HCoV-NL63 infection after a second allogeneic HSCT (allo-HSCT). Six months after the second allo-HSCT, he developed sudden-onset hyperthermia and cough with decreased oxygen saturation. Chest computed tomography (CT) suggested bilateral multiple rounded ground-glass opacities with the pulmonary lobules as units., Diagnoses: HCoV-NL63 was detected by metagenomic next-generation sequencing (NGS), and HCoV-NL63 viral pneumonia was diagnosed., Interventions: The treatment was mainly based on the use of antiviral therapy, hormone administration, and gamma-globulin., Outcomes: After the therapy, the body temperature returned to normal, the chest CT findings had improved on review, and the viral copy number eventually became negative., Lessons: The latest NGS is an effective method for early infection diagnosis. The HCoV-NL63 virus can cause inflammatory factor storm and alter the neutrophil-to-lymphocyte ratio (NLR). This case suggests that the patient's NLR and cytokine levels could be monitored during the clinical treatment to assess the disease and its treatment outcome in a timely manner., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

We report a case of a patient with a relapse of neuromyelitis optica. The relapse was initially treated with intravenous corticosteroids. A therapy with intravenous gamma globulin was started as there was no symptomatic improvement. The patient responded well to the treatment with no significant side effects. Worldwide experience with gamma globulin treatment of neuromyelitis optica is limited and randomised control trials are lacking, therefore accumulation of data from case reports is of paramount importance., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The causative virus of coronavirus disease 2019 (COVID-19) may cause severe fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to acute renal injury due to COVID-19 in patients who have undergone renal transplantation are scarce. We herein report two cases of COVID-19 along with acute kidney injury following kidney transplantation. Case presentation: Two patients with COVID-19 underwent renal transplantation and were subsequently diagnosed with acute kidney injury. The first patient presented with progressive respiratory symptoms and acute renal injury. He was treated with diuretics and suspension of immunosuppressive therapy; however, the patient died. The second patient presented with respiratory tract symptoms, hypoxemia, and progressive deterioration of renal function followed by improvement. Her mycophenolate mofetil was stopped after admission, and tacrolimus was discontinued 10 days later. Moxifloxacin and methylprednisolone were continued in combination with albumin and gamma globulin infusion. A diuretic was administered, and prednisone was gradually reduced along with tacrolimus. The patient exhibited a satisfactory clinical recovery., Conclusion: Patients who develop COVID-19 after kidney transplantation are at risk of acute kidney injury, and their prednisone, immunosuppressant, and gamma globulin treatment must be adjusted according to their condition.

Objective: To explore the curative effects of vancomycin and cefotaxime combined with gamma globulin respectively in neonatal septicemia and their influences on PCT, CRP, and hs-CRP, so as to provide references for clinical treatment., Patients and Methods: 181 patients with neonatal septicemia admitted to Huangshi Maternity and Child Health Hospital from April 2012 to August 2014 were selected as the study subjects. Patients treated with vancomycin combined with gamma globulin were selected as group A (96 cases) and those treated with cefotaxime combined with gamma globulin were selected as group B (85 cases). The improvement time of clinical symptoms (milk rejection, nervous system symptoms, body temperature), hospital stays, mortality, medicine curative effects, adverse reactions, complications, and levels of serum CRP, PCT, and hs-CRP of patients before and after treatment were compared between the two groups., Results: The improvement time of clinical symptoms like body temperature, milk rejection, and neurological symptoms, as well as hospital stays in group A were lower than those in group B (p<0.05); the total effective rate of medicine curative effects in group B was better than that in group A (p<0.05); there was no significant difference in levels of serum CRP, PCT, and hs-CRP between the two groups before treatment (p>0.05); after treatment, levels of serum CRP, PCT, and hs-CRP in both groups decreased significantly, and levels of serum CRP, PCT, and hs-CRP in group B decreased more significantly than those in group A (p<0.05)., Conclusions: Cefotaxime combined with gamma globulin in the treatment of patients with neonatal septicemia has short improvement time in clinical symptoms, high total effective rate of drugs, low mortality, fewer adverse reactions and complications, and can significantly reduce levels of serum CRP, PCT, and hs-CRP, which is worthy of further promotion and application in clinical practice.

The adsorption of γ-globulin was evaluated with experiments with silica particles marketed as Syloid AL1-FP (S AL ), XDP-3150 (S XDP ), and 244FP (S FP ). The influence of pH, pore sizes, and degree of surface porosity on the extent of γ-globulin immobilization was examined. Protein adsorption on these particles was largely related to their surface porosity and pore sizes. The adsorption capacity was established to be greater with mesoporous S FP and S XDP particles at 474 and 377 mg/g, respectively, when compared to significantly low-porosity S AL (16 mg/g). Additionally, γ-globulin immobilization was favored at pH closer to iso-electric point. A key aim of this work was to better understand and improve the limited reversibility of protein adsorption. Protein desorption was found to be lower in simulated intestinal fluid (SIF) in comparison to pH 7.4 phosphate buffer (PB). The use of displacer molecules (sodium dodecyl sulfate [SDS]/Tween 80/Pluronic F127 [PF127]) promoted protein desorption from the adsorbent surface by the exchange mechanism. The PF127 provided substantial release in both studied condition but the highest release of 83% of γ-globulin from S XDP was obtained with tween 80 in PB. The released protein was analyzed with circular dichroism (CD) spectroscopy which indicated that the secondary structure of desorbed γ-globulin was dependent on the pH and displacer molecule. The conformation largely remained unchanged when desorption was carried out in SIF but changed markedly in PB specially in the presence of SDS.

Background: Down syndrome is characterized by a variety of dysmorphic features and congenital malformations, such as congenital heart disease, gastrointestinal disease, and other conditions like leukemia and autoimmune disorders. Patients with Down syndrome are highly prone to respiratory tract infections, which might be fatal to them. However, there are only few available data on patients diagnosed with Down syndrome and agammaglobulinemia. In this report, we describe a case of successful prevention of post-dental treatment complications (e.g., pneumonia and other bacterial infections) in a patient with Down syndrome and agammaglobulinemia., Case Presentation: A 43-year-old man with Down syndrome, untreated agammaglobulinemia, and a history of recurrent pneumonia, was referred to our clinic for tooth mobility. To reduce the risk of post-operative infections, gammaglobulin treatment and prophylactic administration of antibiotics was scheduled before the dental procedure. Furthermore, the dental treatment, which included a filling and extractions, was conducted under general anesthesia and with the supervision of a hematologist. The dental procedures were successfully performed without any post-operative infection, and the patient is undergoing follow-up care., Conclusions: The purpose of this case report was to recommend a close liaison between physicians and dentists who may encounter a similar case, and to emphasize the importance of improving oral health of immunodeficient patients to prevent infections caused by oral microbial flora.

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40-9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

Objective: We hope it will provide a reference for early detection, early diagnosis, and early treatment of atypical Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with non-typical autonomic dysfunctions as the first symptom., Patients and Methods: We present a 15-year-old girl with the repetition of conscious disturbance at different levels, but no abnormal movements. Initially, there were no positive findings on routine electroencephalography (EEG) and dynamic video-electroencephalography (V-EEG), but the head-up tilt test (HTT) suggested neurocardiogenic syncope (vascular rejection type), which seemed to be the final diagnosis. However, the patient later experienced several episodes of disturbance of consciousness with unexplained abdominal pain. Abnormalities were discovered on EEG, which indicated the possibility of "epileptic seizures with autonomic-gastrointestinal features". Based on these findings, we finally tested the autoimmune encephalitis-related antibodies for the patient after the literature search and review., Results: The patient was finally diagnosed with anti-NMDAR encephalitis. Her symptoms were fully controlled after glucocorticoid and gamma globulin treatment, and she left the hospital with complete recovery., Conclusions: Although autonomic nervous dysfunction occurred in our patient, her prognosis was good because she did not have respiratory or (and) circulatory failure. Exclusive diagnosis and early treatment are important in patients with anti-NMDAR encephalitis. Abdominal pain with positive HTT may be a manifestation of autonomic dysfunction in this disease.

Since the wild poliovirus no longer circulates, the number of cases of acute flaccid paralysis decreased. However, cases related to non-polio enteroviruses and neurotrope viruses continue to occur. We present a nine-year-old patient with meningitis and myelitis with motor involvement in the lower limbs and neurogenic bladder associated with enterovirus, with complete resolution of the neurological symptoms following the administration of hyperimmune gammaglobulin., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Rationale: Spinal cord infarction is one of the complications of epidural steroid injections (ESIs), but has only been reported in cervical vertebra by transforaminal injection and lumbar vertebra by transforaminal injection; and up to now, there is no reporting about spinal cord infarction caused by caudal injection. Here, we report a case., Patient Concerns: A 52-year-old man was admitted to our hospital. He was diagnosed as lumbar disc herniation in other hospital, and the patient suffered bilateral lower limb motor and sensory disorders after administration of caudal ESI., Diagnosis: Spinal cord infarction, tethered cord syndrome (TCS), and acute myelitis., Interventions: High doses of hormones, gamma globulin impact therapy, and rehabilitation were performed., Outcomes: The patient's condition was stable when he discharged from the hospital after 20 days of treatment. Discharge status: grade 0 of bilateral lower limbs muscle strength, inability to urinate and defecate by himself, slightly decreased touch, and needling sensation below the umbilical plane., Lessons: When patients are diagnosed with lumbar disc herniation and need to receive invasive treatments, magnetic resonance imaging (MRI) should be performed before the invasive procedures.

Purpose:: To determine if the combination of lidocaine with epinephrine or gamma globulin would decrease the rate or reduce the amount of local absorption of lidocaine through the airway., Methods:: Twenty adult male cats were randomly and evenly distributed into four groups: 1) Group LG: lidocaine administered with gamma globulin; 2) Group LS: lidocaine administered with physiological saline); 3) Group LE: lidocaine administered with epinephrine; 4) Group C: control group. Invasive blood pressure, heart rate, and concentration of lidocaine were recorded before and after administration., Results:: The peak of plasma concentrations appeared difference (Group LG: 1.39 ± 0.23 mg/L; Group LS: 1.47 ± 0.29 mg/L and Group LE: 0.99 ± 0.08 mg/L). Compared to Group C, there were significant differences in the average heart rate of Groups LG, LS, and LE (P < 0.05). The average systolic blood pressures were significantly different when each group was compared to Group C (P < 0.05). The biological half-life, AUC0-120, peak time, and half-life of absorption among the three groups have not presented statistically significant differences (P > 0.05)., Conclusion:: Administering lidocaine in combination with gamma globulin through airway causes significant decrease the rate and reduce the amount of local absorption of lidocaine in cats.

Serum (1→3) beta-D-glucan (BG) measurement is a useful test for systemic mycoses, and often used. On the other hand, various factors, including administration of intravenous immunoglobulins (IVIG) may cause false-positives. In the present study, we measured BG concentration of seven IVIG preparations with three lots respectively. BG levels varied with individual IVIG preparations (<3.0 - >300 pg/mL), and contamination from manufacturing processes was suspected. With serum BG concentration of clinical specimens obtained in Niigata University Medical & Dental Hospital, the difference between before and after administration of IVIG were calculated. The false-positive rate of BG due to IVIG administration was 9.8 %, and the positive predective value was reduced to 37.5%. Above all, administration of IVIG can complicate the BG test's interpretation, and caution is required.

Objective: To investigate the clinical efficacy and safety of intravenous injection of low-dose versus high-dose gamma globulin combined with glucocorticoid pulse therapy in the treatment of children with moderate/severe acute Guillain-Barré syndrome (GBS)., Methods: A total of 100 children with moderate/severe acute GBS were randomly assigned to low-dose group (n=48) and high-dose group (n=52). The children in the low-dose and high-dose groups were treated with 0.2 g/(kg · d) and 0.4 g/(kg · d) gamma globulin respectively combined with methylprednisolone. The two groups were compared in terms of the time to improvements of symptoms after treatment, serum levels of inflammatory factors, proportion of children undergoing invasive ventilation, treatment response rate, and adverse events., Results: After 5 days of treatment, the low- and high-dose groups had significant reductions in serum levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein, and there were no significant differences in the reductions of these markers between the two groups. There were no significant differences between the two groups in the time to recovery of respiratory muscle paralysis, time to an improvement in muscle strength of one grade, time to recovery of sensory disturbance, and length of hospital stay. There was no significant difference in the treatment response rate between the low- and high-dose groups (90% vs 92%). There were also no significant differences in the incidence rates of pyrexia, headache, nausea, and palpitation between the two groups., Conclusions: Low-dose versus high-dose gamma globulin combined with methylprednisolone pulse therapy have comparable clinical efficacy and safety in the treatment of children with moderate/severe acute GBS.

Objective: To study the clinical effect of high-dose gamma globulin pulse therapy for abdominal Henoch-Schönlein purpura (HSP)., Methods: Thirty-three children with abdominal HSP were randomly assigned to dexamethasone group (15 children) and gamma globulin group (18 children). The children in the dexamethasone group were treated with dexamethasone and conventional treatment, and those in the gamma globulin group were treated with high-dose gamma globulin pulse therapy in addition to the conventional treatment. Clinical outcome and recurrence rate were observed in both groups., Results: Compared with the dexamethasone group, the gamma globulin group had a significantly shorter onset time of rash, a significantly shorter time to complete regression of rash, a significantly shorter time to abdominal pain remission, and a significantly shorter time to disappearance of bloody stool, as well as comparable time to vomiting remission and length of hospital stay. The gamma globulin group had a significantly higher response rate than the dexamethasone group (95% vs 65%; P<0.05) and a significantly lower recurrence rate within 6 months than the dexamethasone group (5.6% vs 33.3%; P<0.05)., Conclusions: High-dose gamma globulin pulse therapy has a marked clinical effect in the treatment of abdominal HSP. It is safe and reliable and has a low recurrence rate, and therefore, it holds promise for clinical application.

Objective: Treatment of chronic urticaria (CU) can be difficult in many patients. Achieving long-term remission and reducing the requirement of antihistamines are vital in CU. The objective of this study was to assess the effectiveness of injection histaglobulin, a complex of histamine and human immunoglobulin, in producing relief in patients with CU., Materials and Methods: Fifty-one patients with CU were enrolled into this prospective clinical study. Patients were administered 1 ml of injection histaglobulin subcutaneous for 8 consecutive weeks. They were also prescribed tablet levocetirizine 5 mg to be taken when required (but not more than the permitted dosage). Efficacy was assessed using urticaria activity score (UAS) which has a maximum score of 33/day, during each weekly visit. Final assessment was done after 24 weeks., Results: Twenty-nine patients had completed the entire 8-week drug regimen. Mean basal UAS was 18.9 ± 6.3 and it reduced to 80.4% by 8 weeks. The angioedema sub-score reduced by 89.8%. Anti-histamine pill burden also reduced significantly. By 24 weeks of starting the therapy, 23 patients (45%) had attained complete remission. No adverse effects to the drug were observed., Conclusions: Histaglobulin was found to be effective in producing long-term remission and it reduced the antihistamine requirement as well. Thus, it can serve as an effective alternative to existing treatment modalities.

X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels and clinically by extracellular bacterial infections which mainly compromise the respiratory tract as well as recurrent diarrheas. The mainstay of treatment is gammaglobulin replacement therapy, which allows most patients to reach adulthood with high quality of life. We analyzed the clinical features of 14 patients over 18 years of age with XLA diagnosis that received treatment in our unit from the year 2003, the date the first patient was derived, until 2015. The average age at which patients were referred was 20.4 years old; age at the last consult was 25.5. The average follow-up time was 59.8 months. Previously to being diagnosed all patients had suffered infections, most frequently respiratory. After diagnosis all were started on intravenous gammaglobulin replacement treatment and in spite of infections being reduced in severity and frequency, there were cases of severe disease with long term sequelae. At the beginning of our follow-up 35.7% presented impaired respiratory function with only one case being severe. In no cases during this period did the respiratory function worsen, nor were there severe clinical complications. Three patients were switched to subcutaneous immunoglobulin treatment with good tolerance. The number of XLA cases is increasing, as most reach the second decade of life without serious complications and remain free of severe infectious disease and further impairment of their respiratory functions with the treatment.

Henry K. Beecher was a pioneer of research ethics and a prominent whistleblower with regard to ethically problematic studies. Most of his work focused on research in adults, not children, but he did speculate about the implications of his ethical concerns for research in minors. This paper reviews Beecher's response to Krugman's studies of hepatitis at the Willowbrook State School and the debate that Beecher's article stimulated between Ramsey and McCormick. That debate shaped the terms that were used in current federal regulations for research in children. The paper then speculates about whether Beecher would have approved of our current regulatory system.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated syndrome caused by the production of anti-NMDAR receptor antibodies. The syndrome characterised by psychosis, seizures, sleep disorders, hallucinations and short-term memory loss. Ovarian teratoma is the confirmed tumour associated with anti-NMDAR antibodies. The patients with anti-NMDAR encephalitis complicated by ovarian teratoma require surgical treatment under general anesthesia. NMDARs are important targets of many anesthetic drugs. The perioperative management and complications of anti-NMDAR encephalitis, including hypoventilation, paroxysmal sympathetic hyperactivity (PSH) and epilepsy, are challenging for ansthesiologists., Case Presentation: This report described two female patients who presented for resection of the ovarian teratoma, they had confirmed anti-NMDAR encephalitis accompanied by ovarian teratoma. Two patients received gamma globulin treatments and the resection of the ovarian teratoma under total intravenous anesthesia. They were recovered and discharged on the 20(th) and 46(th) postoperative day respectively., Conclusions: There is insufficient evidence about the perioperative management, monitoring and anesthesia management of anti-NMDAR encephalitis. This report was based on the consideration that controversial anesthetics that likely act on NMDARs should be avoided. Additionally, BIS monitoring should to be prudently applied in anti-NMDAR encephalitis because of abnormal electric encephalography (EEG). Anesthesiologists must be careful with regard to central ventilation dysfunctions and PSH due to anti-NMDAR encephalitis.

Background: Control of rubella is desired because infection in early pregnancy can result in miscarriage, foetal death or congenital abnormality. Primary studies examining the effectiveness of immunoglobulins for post-exposure prophylaxis of rubella have small sample sizes and varying results. National public health recommendations suggest a degree of effectiveness., Objectives: To assess the effectiveness of intramuscular injection or intravenous infusion of polyclonal immunoglobulins of human sera or plasma origin for preventing rubella and congenital rubella syndrome when administered to exposed susceptible people before the onset of disease., Search Methods: We searched CENTRAL (2014, Issue 7), MEDLINE (1946 to August week 2, 2014), EMBASE (1974 to August 2014), CINAHL (1981 to August 2014), LILACS (1982 to August 2014) and Web of Science (1955 to August 2014). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry on 16 October 2014. We searched the reference lists of relevant retrieved reviews and studies and identified national public health guidelines., Selection Criteria: For the outcome 'preventing cases of rubella', we included randomised controlled trials (RCTs) and quasi-RCTs. We found several studies addressing this outcome where the design was a controlled clinical trial (CCT) (with exposure to rubella virus controlled by the investigators) but the method of allocation of participants to groups was not reported. We found an alternative report of one of these studies that indicated participants were assigned to groups randomly. We therefore included such studies as meeting criteria for RCTs or quasi-RCTs and undertook sensitivity analyses. For the outcomes, 'congenital rubella infection' and 'congenital rubella syndrome', we included RCTs, quasi-RCTs and prospective controlled (cohort) studies. Participants were necessarily susceptible and exposed to rubella. Polyclonal immunoglobulins derived from human sera or plasma must have been administered intramuscularly or intravenously as the only intervention in at least one group., Data Collection and Analysis: We used the standard methodological procedures expected by The Cochrane Collaboration., Main Results: We included 12 studies (430 participants) in the review: seven RCTs and five CCTs where it was not clear whether participants were randomly allocated to groups. We did not include any unpublished studies. Participants included children and adults of both sexes. Only one study included pregnant women. All studies were conducted in high-income countries.The quality of the 11 studies in the initial meta-analysis was moderate, although we classified no study as having a low risk of bias on all criteria.We included 11 studies in the initial meta-analysis of gamma-globulin (concentrated polyclonal immunoglobulins) versus control (saline or no treatment) for rubella cases. The result favoured the intervention group (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.45 to 0.83) but was heterogenous (Chi² test = 36.59, df = 10 (P value < 0.0001); I² statistic = 73%). Heterogeneity was explained by subgrouping studies according to the estimated volume of gamma-globulin administered per pound of bodyweight and then removing those studies where the intervention was administered more than five days after participant exposure to rubella (post hoc analysis). The test of subgroup differences demonstrated heterogeneity between subgroups according to our protocol definition (P value < 0.1; I² statistic > 60%) and there appeared to be greater effectiveness of the intervention when a greater volume of gamma-globulin was administered ('0.027 to 0.037 ml/lb' RR 1.60 (95% CI 0.57 to 4.52); '0.1 to 0.15 ml/lb' RR 0.53 (95% CI 0.29 to 0.99); '0.2 to 0.5 ml/lb' RR 0.20 (95% CI 0.04 to 1.00)).None of the studies reported the outcome 'congenital rubella infection'. One included study reported on congenital rubella syndrome, with no cases among participants who were fewer than nine weeks pregnant at enrolment and who were randomised to one of two gamma-globulin groups ('high' or 'low' rubella titre). However, the study did not report how congenital rubella syndrome was measured and did not report the length of follow-up according to intervention group. This study did not include a non-treatment group.No included study measured adverse events., Authors' Conclusions: Compared to no treatment, polyclonal immunoglobulins seem to be of benefit for preventing rubella. The available evidence suggests that this intervention may be of benefit up to five days after exposure, and that effectiveness is dependent on dose. Considering the attack rate for rubella cases in the control group of the highest volume gamma-globulin subgroup (333 per 1000), the absolute risk reduction (calculated from the RR) for this volume of gamma-globulin was 266 (95% CI 0 to 320) and the number needed to treat to benefit is four (95% CI 3 to incalculable).The included studies did not measure rubella-specific antibodies in the immunoglobulin products used in a standard way and thus estimation of the dose of rubella-specific antibodies in international units administered was not possible. As the concentration of rubella-specific antibodies in today's polyclonal immunoglobulin products may vary from those products used in the studies in the review, the volume required per pound of bodyweight to produce similar results may also vary.There is insufficient evidence to make direct conclusions about the effectiveness of polyclonal immunoglobulins for preventing congenital rubella syndrome. This is an area requiring further research.

Adaptive immunity in homeotherms depends greatly on CD4+ Th cells which release cytokines in response to specific antigen stimulation. Whilst bony fish and poikilothermic tetrapods possess cells that express TcR and CD4-related genes (that exist in two forms in teleost fish; termed CD4-1 and CD4-2), to date there is no unequivocal demonstration that cells equivalent to Th exist. Thus, in this study we determined whether CD4-1+ lymphocytes can express cytokines typical of Th cells following antigen specific stimulation, using the zebrafish (Danio rerio). Initially, we analyzed the CD4 locus in zebrafish and found three CD4 homologues, a CD4-1 molecule and two CD4-2 molecules. The zfCD4-1 and zfCD4-2 transcripts were detected in immune organs and were most highly expressed in lymphocytes. A polyclonal antibody to zfCD4-1 was developed and used with an antibody to ZAP70 and revealed double positive cells by immunohistochemistry, and in the Mycobacterium marinum disease model CD4-1+ cells were apparent surrounding the granulomas typical of the infection. Next a prime-boost experiment, using human gamma globulin as antigen, was performed and revealed for the first time in fish that zfCD4-1+ lymphocytes increase the expression of cytokines and master transcription factors relevant to Th1/Th2-type responses as a consequence of boosting with specific antigen.

Hepatitis B is currently an excellent indication for liver transplantation due to the highly effective strategies of prophylaxis and treatment for recurrent hepatitis B infection. The combined administration of low-dose hepatitis B hyperimmune gamma globulin and a nucleoside/nucleotide analogue with a high genetic barrier to resistance, such as entecavir (except for patients with lamivudine resistance) or tenofovir, represents the standard for the prophylaxis of recurrent hepatitis B infection and is used in most centers. The drawbacks of long-term administration of hyperimmune gamma globulin have led to research on regimens in which this agent is withdrawn after a certain amount of time in combination treatment, a strategy that appears to be safe in patients with undetectable viremia at the time of liver transplantation if the patients adhere to the treatment. In recent years, there has also been research into regimens of gamma-globulin-free prophylaxis, based only on the administration of oral antiviral drugs, which appear to be safe if antivirals with a high genetic barrier to resistance are used. Hepatitis B prophylaxis should be maintained indefinitely; therefore, the total withdrawal of prophylaxis is not an accepted strategy at present in daily clinical practice if not in the context of a clinical trial., (Copyright © 2014 Elsevier España, S.L. All rights reserved.)

Background: Measles outbreaks continue to occur in countries with high vaccination coverage. Passive immunisation is generally considered to prevent measles in someone who is not immune and has been exposed to infection. Estimates of effectiveness have varied and no minimum effective dose has been determined., Objectives: To assess the effectiveness and safety of intramuscular injection or intravenous infusion of immunoglobulins (passive immunisation) for preventing measles when administered to exposed susceptible people before the onset of symptoms., Search Methods: We searched CENTRAL (2013, Issue 7), MEDLINE (1946 to July week 5, 2013), CINAHL (1981 to August 2013) and EMBASE (1974 to August 2013)., Selection Criteria: We included randomised controlled trials (RCTs), quasi-RCTs and prospective, controlled (cohort) studies if: participants were susceptible and exposed to measles, polyclonal immunoglobulins derived from human sera or plasma were administered intramuscularly or intravenously as the only intervention in at least one group and the number of subsequent measles cases was measured. We excluded studies of other sources of immunoglobulins., Data Collection and Analysis: Two authors independently extracted data and critically appraised the included studies. We attempted to contact study authors for missing information. We described the results of studies not included in meta-analyses., Main Results: We included one RCT, two quasi-RCTs and 10 cohort studies (3925 participants). No studies were rated as low risk of bias for all criteria. Critical appraisal was constrained by a lack of information in most studies. The overall quality of the evidence was moderate.Seven studies (1432 participants) assessed cases of measles after immunoglobulin versus no treatment. Heterogeneity was explained by subgrouping according to the blood product used as an approximation of dose of immunoglobulin. When given within seven days of exposure, immunoglobulins were effective at preventing measles: gamma globulin (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.08 to 0.36), convalescent serum (RR 0.21, 95% CI 0.15 to 0.29 to RR 0.49, 95% CI 0.44 to 0.54) and adult serum (RR 0.52, 95% CI 0.45 to 0.59). The differences in the effectiveness of different blood products were supported by studies not included in the meta-analysis and by two studies (702 participants) that found gamma globulin more effective than serum (RR 0.56, 95% CI 0.46 to 0.69).Based on three studies (893 participants) immunoglobulin was effective at preventing death due to measles compared to no treatment (RR 0.24, 95% CI 0.13 to 0.44).Two studies included measles vaccine alone among the intervention groups. Meta-analysis could not be undertaken. Both studies suggested the vaccine was more effective than gamma globulin.No serious adverse events were observed in any of the included studies, although reporting of adverse events was poor overall. Non-serious adverse events included transient fever, rash, muscle stiffness, local redness and induration., Authors' Conclusions: Passive immunisation within seven days of exposure is effective at preventing measles, with the risk for non-immune people up to 83% less than if no treatment is given. Given an attack rate of 45 per 1000 (per the control group of the most recent included study), gamma globulin compared to no treatment has an absolute risk reduction (ARR) of 37 per 1000 and a number needed to treat to benefit (NNTB) of 27. Given an attack rate of 759 per 1000 (per the attack rate of the other included study assessing gamma globulin), the ARR of gamma globulin compared to no treatment is 629 and the NNTB is two.It seems the dose of immunoglobulin administered impacts on effectiveness. A minimum effective dose of measles-specific antibodies could not be identified.Passive immunisation is effective at preventing deaths from measles, reducing the risk by 76% compared to no treatment. Whether the benefits of passive immunisation vary among subgroups of non-immune exposed people could not be determined.Due to a paucity of evidence comparing vaccine to passive immunisation, no firm conclusions can be drawn regarding relative effectiveness.The included studies were not specifically designed to detect adverse events.Future research should consider the effectiveness of passive immunisation for preventing measles in high-risk populations such as pregnant women, immunocompromised people and infants. Further efforts should be made to determine the minimum effective dose of measles-specific antibodies for post-exposure prophylaxis and the relative effectiveness of vaccine compared to immunoglobulin.

Pompe disease is a storage disorder characterized by deficient or absent activity of the enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen accumulates in muscle tissues. Patients with a classic infantile-onset form present by the first few months of life with hypertrophic cardiomyopathy and muscle weakness. If left untreated, these patients rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alpha antibody titers. However, CRIM-positive patients also sometimes develop robust antibody titers. High antibody titers complicate therapeutic management, and those patients have a worse clinical outcome of enzyme replacement therapy (ERT).Four years ago, we successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom ERT had to be discontinued because of severe infusion-associated reactions. She was found to be positive for anti-alglucosidase alpha antibodies. IMT (rituximab, methotrexate, and intravenous gammaglobulin) was started, and ERT was safely reintroduced during the IMT induction phase without any complications. Antibodies disappeared; IMT was tapered and discontinued; and cardiomyopathy steadily improved. During more than 3 years of follow-up, she remained ventilator dependent, and no gains in motor skills were noticed. The antibodies are still undetectable, and no adverse reactions associated with IMT had occurred. The cardiomyopathy is gradually increasing, but there is still ~ 50 % reduction as compared with the highest value measured. Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant cannot be solely attributed to IMT, this protocol proved itself efficient and safe.

Ectopic cervical thymoma (ECT) is a rare tumor that is frequently misdiagnosed as a thyroid tumor or other malignancy. A 34-year-old male with a right palpable neck mass had been mistakenly diagnosed with T-cell lymphoblastic lymphoma even after an open biopsy. The atypical clinical course, including hypogammaglobulinemia, led us to the correct diagnosis; ECT accompanied by Good's syndrome (GS). After the intravenous infusion of gammaglobulin, tumor resection and a subsequent video-assisted thoracoscopic extended thymectomy were performed. The final diagnosis was type AB thymoma, Masaoka stage I. This report is, to the best of our knowledge, the first description of this extremely rare combination.

Common variable immunodeficiency (CVID) is a common primary immunodeficiency characterized by a failure in B-cell differentiation with defective immunoglobulin production. Affected patients are uniquely susceptible to recurrent infection with encapsulated organisms and have an increased propensity for the development of inflammatory and autoimmune manifestations. The diagnosis of CVID is commonly delayed and the underlying cause of the disorder is not understood. Replacement antibody therapy reduces the risk of serious infections. However, optimal treatment regimens for the uncommon manifestations associated with this disease, such as granulomatous lymphocytic interstitial lung disease, require further research.

Intravenous immunoglobulins (IVIGs) are used for a variety of immunologic and hematologic disorders. Hemorheologic alteration or the rapid increase of platelet counts by IVIG administration can cause thrombotic adverse events. We present a 58-year-old woman with a previous diagnosis of idiopathic thrombocytopenic purpura who developed cerebellar infarction immediately after IVIG treatment. We discuss a possible role of IVIG in cerebral ischemia and management strategies., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Introduction: The risk of hepatitis B virus (HBV) transmission through donor organs with HBsAg(-) and anti-HBc(+) serology has not been extensively studied in lung transplantation. The objectives of this study are to ascertain the influence of the anti-HBc(+) on the acceptance of the lung for transplantation, to comment on the published literature and to suggest an algorithm for action., Methods: A survey conducted in the 7 Spanish lung transplantation teams. The updated search of the literature was performed using medical databases from 1994 to February 2012., Results: All of the teams vaccinate the lung recipients against HBV, although none quantify the anti-HBs titers. When given an anti-HBc(+) donor, 3 teams change their strategy: one does not accept the offer, one selects the receptor from among patients in emergency status and another adds pharmacological prophylaxis. Only 3 publications refer to the serologic evolution of the receptors. At the moment there have been no reported cases of hepatitis B or HBsAg positivity post-transplant, but 4 out of the 50 anti-HBc(-) receptors changed to anti-HBc(+) in the follow-up., Conclusions: The presence of anti-HBc in the donor influences the decision to accept a lung donor, although there is little information on its repercussions. To date, there has been no reported case of transmission of HBV, but post-transplant anti-HBc seroconversions have been described, which suggests contact with viral particles. Although rare, an anti-HBc(+) donor can harbor a hidden HBV infection. The risk of infection can be reduced with adequate anti-HBs titers or with appropriate pharmacological measures., (Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.)

Purpose of Review: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which T and B cells recognize platelet antigens and initiate antiplatelet destructive mechanisms such as peripheral Fc receptor-mediated phagocytosis in the spleen or megakaryocyte destruction/inhibition within the bone marrow. The purpose of this review is to report on the ITP pathophysiology literature published from January 2011 to early in 2012., Recent Findings: The underlying stimulus of platelet autoimmunity is not known; however, in 2011, as in previous years, there has been a significant contribution of published studies addressing the pathophysiology of ITP. At least half of the 2011 ITP pathophysiology literature was associated with T-cell dysregulation particularly with respect to T-helper 17 cell and related cytokine and genetic studies. There were also studies related to B-cell responses, human spleen cells and the potential role of oxidative stress in ITP. With respect to therapeutic research, the mechanisms of action of intravenous gammaglobulin relating to Fc inhibitory receptors and sialylation have been challenged., Summary: The overall landscape of pathophysiological research into ITP still is overwhelmed by studies on abnormal T-cell responses and these studies are beginning to clarify the underlying immune mechanisms that are responsible for the disorder.

It was stated, that with bilateral photochemically induced thrombosis of the prefrontal cortex peptide semax and the AB-Glu by intranasal injection provoke pronounced neuroprotective and antiamnestic action. Intranasal injection semax (250 mkg/kg/daily during six postoperative days) and AB-Glu (250 mkg/kg in 1 hour after phototrombosis) demonstrate diminishing of cortex damage volume and relieve preservation and reproduction rat passive avoidance reflex, acquired before bilateral photochemically induced thrombosis of prefrontal cortex.

A 66-year-old male was hospitalized with muscle weakness and gait disturbance. Examination revealed IgM 3,407 mg/dl (IgM, κ-type M protein) and he was diagnosed as having IgM-MGUS neuropathy. He suffered from paralysis of respiratory muscles and required a respirator support. Plasmapheresis and intravenous immunoglobulin were performed and he was weaned from the respirator. Rituximab given as 8 weekly infusions improved gait disturbance. A 71-year-old male was hospitalized with lumbago, numbness of lower extremities and gait disturbance. Examination revealed IgM 1,553 mg/dl (IgM, λ-type M protein) and he was diagnosed with IgM-MGUS neuropathy. Rituximab given as 8 weekly infusions improved gait disturbance. It was concluded that rituximab is a well-tolerated treatment that may be effective in some patients with IgM-MGUS neuropathy.

Anaphylactic reactions to immunoglobulin infusions in immunodeficient patients with undetectable IgA have been attributed in several reports to IgG or IgE anti-IgA antibodies. However, other reports have not supported an association between such antibodies and the development of severe reactions. We have reviewed the articles reporting reactions to immunoglobulin products in IgA-deficient patients, as well as those describing the presence of such antibodies in the absence of reactions to infusions. A variety of factors might influence the association of adverse reactions with anti-IgA antibodies, including the serum concentration and isotype (IgG or IgE) of the anti-IgA antibody, its specificity (class or subclass specific), the method of measurement, and the IgA content of the gamma globulin infusion and its route of administration. The role of anti-IgA antibodies in causing anaphylaxis in IgA-deficient patients receiving gamma globulin therapy is still controversial. Larger (multicenter) studies are needed to further evaluate this association., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis., Methods: Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14., Results: Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment., Conclusion: This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes.

Since the 1999 US Food and Drug Administration (FDA) warning of renal failure/dysfunction associated with intravenous gammaglobulin (IVIg), there has been a movement towards developing safer, more convenient formulations. Until now, the scope of renal failure associated with IVIg, has not been well described. The FDA Adverse Event Reporting System (AERS) from 2004 through 2009 was examined for renal impairment reactions due to IVIg and associated demographic features, comorbidities and indications. Anaphylaxis cases associated with IVIg administration were used as a comparison group. There were 90 renal impairment cases associated with IVIg administration. Neuromuscular disorders (33/37%) and hematologic disorders (32/36%) were the predominant treatment indications. When reported anaphylaxis versus renal impairment due to IVIg was examined as a binary outcome in logistic regression modeling, renal impairment was predicted by sucrose presence, increasing age and non-hypogammaglobulinemic indications. Of the 34 hemodialysis cases, the excipient was known in 28 and all but 1 consisted of sucrose. IVIg containing sucrose was used in 33 of 48 nonhemodialysis cases. More hemodialysis cases also had diabetes mellitus. When the interval between renal impairment and the first IVIg infusion was determined, the renal impairment was reported by the second day in 43.3% of cases, and between 3 and 5 days in 41.7% of cases. Despite an evolution in clinical usage and formulations, renal impairment after IVIg administration continues to be reported. Sucrose as the excipient in IVIg plays a major role, but other factors are also important. These findings have implications in the management of patients treated with IVIg.

A 64-year-old man with a 10-year history of Good syndrome had been treated with periodic replacement of γ-globulin. He also had a 6-year history of lichen planus of the tongue. In 2009, the patient was diagnosed as having pure red cell aplasia (PRCA) based on bone marrow aspiration. Thymectomy was not effective. Then, immunosuppressive therapy with PSL and cyclosporine was initiated. Twenty days after treatment painful ulcer appeared on the left side of the tongue. Biopsy specimen of the ulcer demonstrated cells infected with cytomegalovirus and herpes simplex virus. Cytomegalovirus antigenemia was also positive. The tongue ulcer promptly improved after gancyclovir administration for a few weeks. Viral glossitis should be considered as part of the differential diagnoses of oral lesions not only in patients with HIV infection but also in those under immunosuppressive therapy.

In contrast to normal mice, autoimmune-prone New Zealand Black (NZB) mice are defective in susceptibility to tolerance induced by deaggregated bovine γ globulin (DBGG). To examine whether this defect is related to the loss of self-tolerance in autoimmunity, susceptibility loci for this defect were examined by genome-wide analysis using the F(2) intercross of nonautoimmune C57BL/6 (B6) and NZB mice. One NZB locus on the telomeric chromosome 1, designated Dit (Defective immune tolerance)-1, showed a highly significant linkage. This locus overlapped with a locus containing susceptibility genes for autoimmune disease, namely Fcgr2b and Slam family genes. To investigate the involvement of these genes in the defective tolerance to DBGG, we took advantage of two lines of Fcgr2b-deficient B6 congenic mice: one carries autoimmune-type, and the other carries B6-type, Slam family genes. Defective tolerance was observed only in Fcgr2b-deficient mice with autoimmune-type Slam family genes, indicating that epistatic effects of both genes are involved. Thus, common genetic mechanisms may underlie the defect in foreign protein antigen-induced tolerance and the loss of self-tolerance in NZB mouse-related autoimmune diseases., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epistasis is fast becoming central to the understanding of the complex relationship between genotype and phenotype observed in autoimmune disease. A study in this issue of the European Journal of Immunology uses in-depth analysis of genome-wide mapping by polymorphic microsatellite markers to shed light on the genomic control of autoimmunity and self-tolerance., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Kawasaki disease, a systemic vasculitis of unknown etiology, develops frequently in infants and demonstrates a variety of clinical symptoms during the disease course. The most important complication, coronary artery lesions, is found in 15-25% of untreated patients. Meanwhile, acute myocarditis, another complication that can occur during the acute phase of severe systemic vasculitis, has been found in more than 50% of affected individuals when asymptomatic cases are included. However, cases that require treatment are rare as reported by Yoshikawa et al. (Circ J 70:202-205, 2006). As for neural complications, aseptic meningitis is well known, but it is extremely rare for these patients to develop encephalitis or encephalopathy as reported by Imai et al. (Jpn Soc Emerg Pediatr 8:50-55, 2009). Recently reported magnetic resonance images (MRIs) have shown reversible lesions in the median splenium of patients complicated with encephalitis or encephalopathy. Reversible lesions have also been observed after the administration of an antiepileptic agent, drastic weight loss, and development of metabolic abnormalities as reported by Massimo et al. (Neuroradiology 49:541-544, 2007) and Tada et al. (Neurology 63:1854-1858, 2004). Aggressive therapy for such lesions is not considered necessary because most disappear without neurologic aftereffects. However, the clinical significance and pathogenesis of the condition remain largely unknown. We present the first known report of a Kawasaki disease case complicated with acute myocarditis and mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). These findings may be valuable for the diagnosis and treatment of affected patients.

Development of long-term humoral immunity, characterized by the formation of long-lived plasma cells (PCs) in the bone marrow and memory B cells, is a critical component of protective immunity to pathogens, and as such it is the major goal of vaccination. However, the mechanisms involved in the generation of long-term humoral immunity remain poorly understood. In this study, we used IL-21R-deficient (IL-21R.KO) mice to examine the role of the IL-21 pathway in the development of the B cell memory response. Primary IgG serum Ab responses to the T cell-dependent Ag 4-hydroxy-3-nitrophenylacetyl (NP) hapten conjugated to chicken γ globulin were delayed in IL-21R.KO mice, but reached normal titers within 3 to 4 wk of immunization. IL-21R.KO mice formed germinal centers and generated normal numbers of PCs in their bone marrow. Additionally, memory B cell formation was similar in wild-type and IL-21R.KO mice. However, NP-specific memory B cells and PCs failed to expand following secondary immunization of IL-21R.KO mice, and consequently, secondary IgG Ab responses to NP hapten conjugated to chicken γ globulin were significantly impaired. These results identify the IL-21 pathway as a critical component of the memory B cell response.

This case report describes polymyxin B-immobilized fiber (PMX-F) treatment of septic shock caused by pyelonephritis in a 68-year-old woman with autosomal dominant polycystic kidney disease. She was admitted for severe lower left abdominal pain, high fever (40°C) and gross hematuria. Her endotoxin and high-mobility group box-1 protein (HMGB1) levels were extremely elevated. Her blood pressure was 68/36 mm Hg. Urinalysis revealed innumerable white blood cells (WBCs). Blood and urine cultures were positive for Klebsiella pneumoniae and Pseudomonas aeruginosa. Plain abdominal radiography showed large kidney shadows and calcium deposition. Septic shock with endotoxemia was diagnosed. Her symptoms of septic shock persisted for 3 days with antibiotics, γ-globulin and dopamine. Direct hemoperfusion was performed twice with a PMX-F column. The patient's body temperature, WBC count and C-reactive protein level decreased. Her blood endotoxin level and blood HMGB1 level also decreased to an almost normal level. She was discharged on day 23 after admission., (Copyright © 2011 S. Karger AG, Basel.)

Mechanisms by which cell surface levels of the BCR are regulated remain largely unknown. We found that B cells lacking the lysosomal-associated protein transmembrane 5 (LAPTM5) expressed higher levels of cell surface BCR than did wild-type (WT) B cells after Ag stimulation in vitro and in vivo. In addition, LAPTM5-deficient mice contained an increased frequency of Ag-specific B cells and produced greater amounts of Abs than did WT mice after immunization with a T-dependent Ag. Adoptive transfer of LAPTM5-deficient B cells with WT T cells into RAG1-deficient mice revealed that the increased surface BCR levels and the enhanced B cell activation and Ab production were due to a B cell intrinsic defect. As they aged, the LAPTM5-deficient mice had increased titers of serum IgM and autoantibodies and immune complex deposition in the kidney. Immunofluorescent and biochemical analysis revealed that LAPTM5 physically interacted with the BCR complex and promoted its degradation in the lysosomal compartment in mouse B cells. These results demonstrate a role for LAPTM5 in the negative regulation of cell surface BCR levels and B cell activation.

Objective: To investigate the etiology and perinatal outcome of pregnancies complicated with extremely severe thrombocytopenia [at least two times of platelets count (PLT) < 10 × 10(9)/L during pregnancy]., Methods: Clinical data, including basic information, etiology, management and outcomes of pregnant women with extremely severe thrombocytopenia, admitted to Peking University People's Hospital from January 2004 to March 2009, were retrospectively collected. The management of these cases varied according to different etiology and the symptoms: (1) PLT were maintained > 20 × 10(9)/L and hemoglobulin > 70 g/L in those women without spontaneous bleeding; (2) PLT transfusion would be required when PLT < 10 × 10(9)/L or bleeding occur and RBC would be supplied when hematocrit < 25% and hemoglobulin < 70 g/L; (3) Hemoglobulin should be > 70 g/L and PLT > 30 × 10(9)/L before cesarean section or delivery; (4) Predinisone and/or intravenous immunoglobulin G (IVIG) would be given in women complicated with idiopathic thrombocytopenic purpura (ITP) when PLT < (20 - 30) × 10(9)/L or bleeding. PLT would be given if all the above management were failed, or PLT < 10 × 10(9)/L, or bleeding. Women without bleeding would be closely monitored and delivery would be planned., Results: (1) Twenty-six cases were identified among 9302 deliveries during the study period (0.28%), with an average of maternal age of 29. Seventeen were diagnosed before conception and 9 during pregnancy. Among the 26 women, half received regular prenatal check in our hospital and the average gestations at diagnosis was 24 weeks and the other half without regular prenatal visits and the average gestations at diagnosis was 32 weeks. Etiology was identified in 24 out of the 26 women, including 14 (54%) ITP, 5 myelodysplastic syndrome (MDS), 4 chronic aplastic anaemia (CAA) and 1 systemic lupus erythematosus (SLE). (2) MANAGEMENT: All of the 26 women received blood products. Among the 14 ITP cases, 6 received predinisone and IVIG and 8 only took predinisone. Nine of the 26 patients (35%) had pregnant complications, among which 6 (6/9) were preeclampsia. The overall average gestation at delivery was 36 weeks. Only 2 delivered vaginally with the average blood loss of 83 ml and 23 cesarean sections were performed with the average blood loss of 410 ml. (3) Perinatal outcomes: There were 26 perinatal babies, among which 1 died intrauterine and 25 were born alive (12 preterm infants). The average birth weight was 2877 g. Neonatal severe thrombocytopenia presented in 2 newborns whose mother complicated with ITP., Conclusions: The main cause of extremely severe thrombocytopenia during pregnancy is ITP, managed mainly by predinisone and IVIG, followed by CAA and MDS, which may require supportive treatment. Pregnancy complicated with extremely severe thrombocytopenia is not an indication of termination. Better maternal and fetal outcomes can be achieved through proper treatment based on the etiology, intensive care in prevention and management of complications and cesarean section.

Introduction: The clinical manifestations and risk factors for developing coronary artery abnormalities (CAA) in Kawasaki disease (KD) might differ depending on age., Materials and Methods: From January 2001 to July 2007, 161 patients with an age younger than 1 year (younger group) and 60 patients with an age older than 5 years (older group) were diagnosed with KD at the Korea University Medical Center. Their medical records were reviewed retrospectively and the two groups were compared in terms of a number of variables commonly associated with the development of CAA, including clinical manifestations and laboratory findings., Results: While the overall incidence of KD-associated CAA in our hospital was 6.7%, CAA developed in 20 (12.4%) of the younger group and ten (16.7%) of the older group, respectively. The CAA (+) cases of the younger group had a longer duration of total fever (9.1 +/- 3.3 vs 6.3 +/- 1.9 days, p = 0.002) and showed fewer diagnostic symptoms (3.0 +/- 1.2 vs 4.3 +/- 1.1, p < 0.001) than the CAA (-) cases. The CAA (+) cases of the older group had a longer duration of total fever (14.1 +/- 10.4 vs 6.5 +/- 1.9 days, p = 0.045), especially with respect to post-intravenous gamma globulin (IVGG) fever (7.9 +/- 9.6 vs 1.1 +/- 0.8 days, p = 0.052), and had higher total white blood cell counts, erythrocyte sedimentation rates, C-reactive protein levels, total bilirubin levels, and Harada scores and lower serum albumin and sodium levels than the CAA (-) cases. Multivariable logistic regression analysis revealed that the factors that were associated significantly with the development of CAA were the number of total symptoms (OR = 0.494, 95% confidence interval (CI) = 0.281-0.871, p = 0.015) in the younger group and the duration of post-IVGG fever (OR = 1.958, 95% CI = 1.098-3.492, p = 0.023) and the Harada score (OR = 3.455, 95% CI = 1.012-11.796, p = 0.048) in the older group., Conclusion: Incomplete clinical manifestations in the younger group and IVGG nonresponsiveness in the older group are associated with the development of KD-associated CAA. These age-specific characteristics could aid the customization of the diagnostic and therapeutic strategies of KD, thereby helping to improve the outcome of this disease.

Objective: To compare the rates of intravenous gamma globulin (IVIG) non-responder and coronary complication among early, conventional and late IVIG treatment in children with Kawasaki disease (KD)., Methods: All children with KD and IVIG treatment were retrospectively analyzed at 45 hospitals in Beijing during the 5-year period from 2000 through 2004. The time of IVIG treatment was classified as early (Day 1 - 4), conventional (Day 5 - 9) and late treatment group (Day 10 or later). The efficacy of IVIG was judged by the rate of IVIG non-responder. Echocardiography was used to assess the coronary complication at acute (1 - 2 weeks after onset) and sub-acute (3 - 6 weeks after onset) stage., Results: A total of 1052 patients (680 boys, 372 girls) aged 2 months to 13.8 years were included. They were grouped as early, conventional and late treatment in 108, 763 and 181 children respectively. The rate of IVIG non-responders was higher in early (28.7%, 31/108) as compared with conventional (11.9%, 91/763) and late treatment group (7.2%, 13/181, both P < 0.01). The incidences of coronary complications were similar in early (17.6%, 19/108 and 5.9%, 4/68) and conventional treatment group (18.3%, 140/ 763 and 5.5%, 25/452), while significantly higher in late treatment group (33.7%, 61/181 and 12.8%, 15/117) in acute and sub-acute stages (both P < 0.01)., Conclusions: IVIG treatment in children with KD for a disease duration of 1 - 4 days appeared to increase the rate of IVIG non-responders. Children with IVIG given at Day 10 or later had a higher incidence of acute and sub-acute coronary complications. IVIG given at Day 5 - 9 seems to be the best time for IVIG therapy in KD.