Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis

BACKGROUND: It is suggested that the highly cation-charged fraction of the IgG and IgG3 subclasses may play a pathogenic role in lupus nephritis. In contrast, immunoadsorbent therapy using a sodium dextransulfate fixed cellulose gel column-low invasive selective immunoadsorbent apheresis therapy (SDSC-IAT) has been applied to lupus nephritis with favorable results. However, elimination using pathogenic IgG by SDSC-IAT has never been investigated. METHOD: Two patients with diffuse proliferative lupus nephritis were treated using SDSC-IAT concomitant with immunosuppressive therapy. The eluates from the SDSC, and the patients' serum obtained before and just after SDSC-IAT were subjected to an IgG charge analysis using isoelectric focusing and immunoblotting, and also to laser nephelometry assay, which is used for measuring IgG subclass concentration. Indirect immunofluorescence staining was performed to detect IgG subclass deposition in the glomerulus. RESULTS: Both of the patients had an immediate decrease in anti-double-strand DNA antibody and in the circulating immune complex with a following clinical improvement. Repeated biopsies demonstrated improvement of glomerular lesions with a marked reduction of IgG and C3 deposition. The IgG of the SDSC eluates consisted of highly cation charged (isoelectric points: 9-10) fractions. In addition, IgG3 was specifically removed from the patients' serum using an SDSC among the IgG subclasses. The subclass of deposited IgG in the glomeruli showed IgG3 predominance. CONCLUSION: SDSC-IAT specifically removed the highly cation charged fractions of IgG and IgG3 from the patients' serum and the elimination of these fractions may have resulted in clinical improvement.     

Evidence for a human IgG1 class switch program

In activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1-expressing human B cells, immortalized by Epstein-Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1-expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.     

Immunoglobulin G4 antibodies to rat urinary allergens, sensitization and symptomatic allergy in laboratory animal workers

BACKGROUND AND OBJECTIVES: We have previously reported that high rat urinary allergen (RUA) exposure was not associated with increased risk of rat allergy in long-term-exposed laboratory animal (LA) workers. We aimed to assess whether strong allergen-specific IgG4 responses could explain the absence of a dose response in these subjects. We investigated whether IgG4 was associated with allergen exposure and prevalence of sensitization or respiratory symptoms to rats. The longitudinal relation between IgG4 and rat allergy was studied using data obtained during 2 years of follow-up. METHODS: Five hundred and twenty-nine LA workers answered a questionnaire on respiratory symptoms and occupational history and participated in skin prick testing. Blood samples were analysed for specific IgG4 and IgE to RUA. Exposure to RUA was estimated based on personal air samples. The relation between IgG4 and newly occurring sensitization or rat allergy was studied in workers who were not sensitized or did not report respiratory symptoms to rats. RESULTS: IgG4 titres were higher in atopic than in non-atopic subjects, and increased with higher allergen exposure. Titres were highest in subjects who were sensitized and reported respiratory symptoms to rats when compared with those who were not (geometric mean [geometric standard deviation] = 202 [5.7] vs. 8.4 [18.3] AU). The association between IgG4 and sensitization or symptomatic rat allergy was independent of estimated allergen exposure. IgG4 was a strong predictor of newly occurring sensitization and symptomatic rat allergy during follow-up in atopic and rat-sensitized subjects. CONCLUSION: High exposure to RUA is associated with a strong allergen-specific IgG4 antibody response. High anti-RUA IgG4 is a strong predictor of prevalent and incident sensitization and symptomatic rat allergy in atopic and rat-sensitized subjects. IgG4 can therefore not explain the absence of a dose response between allergen exposure and allergy in long-term-exposed workers. We consider anti-RUA IgG4 to be a marker that combines aspects of exposure and susceptibility.     

Intrathecal synthesis of anti-myelin basic protein IgG in HIV-1+ patients

Human immunodeficiency virus type 1 (HIV-1)-infected individuals frequently develop a broad spectrum of neurological syndromes, classified as HIV-1-associated cognitive/motor complex. Diffuse demyelination of hemispheric white matter is a commonly observed in HIV-1 infected brain, but the events leading to myelin destruction are still obscure. Since oligodendrocyte infection by HIV-1 is not proven as yet, myelin damage in HIV-1 infection may result from indirect mechanisms such as the excessive release of myelinotoxic substances or the triggering of autoimmune responses directed to myelin constituents. To verify the latter hypothesis, we searched for elevated anti-myelin basic protein (MBP) IgG levels in the cerebrospinal fluid (CSF) and serum of 25 patients with HIV-1 infection, 12 with multiple sclerosis (MS), and 9 with non-inflammatory neurological diseases (NIND). CSF, but not serum, anti-MBP IgG levels were more frequently elevated in HIV-1⁺ (16/25, 64%) than in MS (3/12, 25%) or NIND (0/9) patients. By using the anti-MBP IgG index, the anti-MBP IgG antibody specificity index (ASI), and the search for anti-MBP oligoclonal IgG, we ascertained that anti-MBP IgG were produced within the CNS in 13 of 25 (52%) HIV-1⁺, in 6 of 12 (50%) MS, and in none of NIND patients. The incidence of increased CSF anti-MBP IgG levels was higher among HIV-1⁺ patients at stage II–III (4/4, 100%) or at stage IV B (7/9, 78%) than among those at stage IV C–IV D (5/12, 42%). Although our data indicate that intrathecal anti-MBP IgG may occur early during HIV-1 infection and that they are more common in patients with HIV-1-associated cognitive/motor complex, the possible demyelinating role of these antibodies remains to be demonstrated.     

Humoral immunity to Malassezia furfur serovars A, B and C in patients with pityriasis versicolor, seborrheic dermatitis and controls

Abstract This study examined the humoral immune responses to Malassezia furfur serovars A, B and C of 10 patients with pityriasis versicolor, 10 patients with seborrheic dermatitis and 20 age- and sex-matched controls. A transferable solid-phase ELISA was used to determine titres of total Igs, IgM, IgA and IgG specific to M. furfur serovars A, B and C. The results demonstrated that patients with seborrheic dermatitis had a significantly higher litre of total Igs to serovar A than patients with pityriasis versicolor; and that patients with seborrheic dermatitis had a significantly higher litre of IgA to serovar C than patients with pityriasis versicolor. The litres of total Igs for controls and patienls with seborrheic dermatitis were significantly lower to serovar B than to serovar C. A modified TSP ELISA was used to determine the titres of the IgG subclasses. Titres of IgG _1,3,4 to serovar B were significantly higher in seborrheic dermatitis patients than pityriasis versicolor patients and litres of IgG₃, to serovar A were significantly higher in seborrheic dermatitis patients than pityriasis versicolor patients. However, despite the differences between the patient groups, none of these results was significantly different to those of controls. Thus, this study did not demonstrate any differences in humoral immunity of patients suffering from Malassezia-associated dermatoses when compared to normal controls. These results may suggest that the humoral immune response to M. furfur is not related to the pathogenesis of Malassezia-associated dermatoses, but simply to the carriage of M. furfur on the skin.     

Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.     

长沙地区孕妇CMV感染状况及其临床追踪观察

研究了７７例长沙地区孕、产妇的宫颈排毒（ＣＭＶ）情况及母、婴的免疫状态，并对宫颈排毒及ＣＭＶ一ＩｇＭ阳性的母亲所生小孩进行临床追踪。结果显示：孕妇宫颈排毒率为４．５％，抗ＣＭＶ－ＩｇＧ和抗ＣＭＶ－ＩｇＭ阳性率分别为７７％和１３％，５９例脐血ＣＭＶ－ＩｇＭ阴性。宫颈排毒的３例其抗体检测抗ＣＭＶ－ＩｇＧ均阳性，抗ＣＭＶ－ＩｇＭ仅一例阳性。作者认为，对妊娠期活动性ＣＭＶ感染的诊断，仅检测抗ＣＭＶ－ＩｇＧ和抗ＣＭＶ－ＩｇＭ抗体滴度仍不足，尚须结合病毒分离和其它检测手段。     

哮喘模型豚鼠变态反应机制的实验研究

目的 :观察哮喘豚鼠的变态反应机制是否与人体一致。方法 :健康豚鼠 2 4只 ,随机分为空白组、模型组、药物内服组。以血清总IgE、IgG、IL - 4为效应指标 ,观察 3组动物效应指标的变化。 结果 :各组动物血清总IgE水平没有发生显著性变化 ,模型组与空白组比较 ,IgG含量较空白组显著降低(P <0 .0 5 ) ,IL - 4含量显著升高 (P <0 .0 5 ) ,经药物治疗后 ,IgG含量明显增高 (P <0 .0 5 ) ,IL - 4含量则明显下降 (P <0 .0 5 )。结论 :豚鼠的哮喘是由IgG介导的变态反应 ,与人体哮喘由IgE介导的病理机制有所不同 ,建议实验应用豚鼠哮喘模型应当受到限制。     

A Quantitative Study of Specific Immunoglobulins to Mosquito Salivary Gland Antigen in Hypersensitive and Common Types of Mosquito Bite Reaction

This study was designed with two purposes: first, to elucidate immunologic mechanisms in different cutaneous reactions, particularly in hypersensitivity to mosquito bites, and, second, to develop a more reliable and safer method of identifying the causative species of mosquito in severe cases. The amounts of IgG, IgG₄ and IgE specific to the mosquito salivary gland extract of Aedes albopictus were determined in the sera of 116 volunteers with normal reactions, either immediate or delayed, and 4 patients with severe systemic symptoms caused by mosquito bites. Titers of IgG and IgE in the severe cases were considerably higher than in volunteers with normal reactions, but there were no differences in IgG, titers between the two groups. These results indicate that high titers of IgG and IgE may be involved in development of systemic symptoms in severe cases and verify the possibility of in vitro tests to identify causative species of the mosquito.     

Prevalence and estimated incidence of Toxoplasma infection among pregnant women in Poland: a decreasing trend in the younger population

This study investigated the prevalence of specific Toxoplasma gondii IgG in pregnancy, the incidence of congenital toxoplasmosis and the prevalence trend of T. gondii infection among pregnant Polish women between 1998 and 2003. The study population comprised 4916 women who were admitted to the Polish Mother's Memorial Hospital Research Institute in Łódź. Their sera were tested for specific IgG and IgM antibodies to T. gondii, and the incidence of T. gondii infection was calculated from the increase in prevalence rates of IgG antibodies in various age groups. Specific IgG antibody was found in 41.3% (95% CI 39.9–42.7) of pregnant women, and the prevalence of IgG increased with age. The linear trend was significant (p <0.001), with an annual seroconversion rate of 0.7% (95% CI 0.004–0.010). The risk of primary infection was estimated to be 0.5% for 9 months, i.e., an incidence of 5/1000 pregnancies. Assuming a 30% maternofetal transmission rate, 1.5/1000 neonates were infected in utero. Seroprevalence during the 6-year study period decreased from 45.4% in 1998 to 39.4% in 2003, with a yearly decline in prevalence of 1.0% (p 0.02). The most important contributory factor to this decline was the group of women aged 19–29 years, among whom seroprevalence decreased significantly (p 0.007). Specific IgM was found in 244 (4.9%) women.