HtrA, RseP, and Tsp do not elicit a pathology related serum IgG response during sexually transmitted infection with Chlamydia trachomatis

Chlamydia trachomatis sexually transmitted infection can cause serious reproductive morbidities. This study determined the prevalence of serum IgG response to C. trachomatis putative stress response proteins in females to test for an association with genital tract pathology. There was no significant association of serum IgG to HtrA, Tsp, or RseP with infection or pathology. cHSP60 serum IgG prevalence was significantly associated with infection compared to negative (infertile) controls (p = 0.002), but not with upper genital tract pathology. Serum IgG1-4 antibody subclasses reactive with the antigens was not significantly different between cohorts, although different responses to each antigen were detected.

Transport of IgG across the blood-luminal barrier of the male reproductive tract of the rat and the effect of estradiol administration on reabsorption of fluid and IgG by the epididymal ducts

In rats immunized systemically with tetanus toxoid the concentration of specific anti-tetanus-toxoid-specific IgG in fluid from the rete testis and cauda epididymidis were respectively 0.6% and 1.4% the concentration in blood serum. The extratesticular duct system reabsorbed 97% of the IgG and 99% of the fluid leaving the rete, but estradiol administration affected the site of reabsorption. In untreated rats, the ductuli efferentes reabsorbed 94% of the IgG and 96% of the fluid leaving the rete, whereas estradiol-treated rats reabsorbed 83% of the IgG and 86% of the fluid, and the ductus epididymidis fully compensated for these different effects of estradiol on the ductuli efferentes. The concentrations of IgG in secretions of the seminal vesicles and prostate gland were lower (0.1% and 0.3% respectively of the titers in blood serum) than in fluids from the extratesticular ducts, and were not affected by the administration of estradiol. RT-PCR showed that Fcgrt (neonatal Fc receptor, also known as FcRn) is expressed in the reproductive ducts, where IgG is probably transported across epithelium, being particularly strong in the ductuli efferentes (where most IgG was reabsorbed) and distal caput epididymidis. It is concluded that IgG enters the rete testis and is concentrated only 2.5-fold along the extratesticular duct system, unlike spermatozoa, which are concentrated 95-fold. Further, the ductus epididymidis can recognize and compensate for changes in function of the ductuli efferentes.

Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

Antibodies can play a protective but non-essential role in natural chlamydial infections dependent on antigen specificity and antibody isotype. IgG is the dominant antibody in both male and female reproductive tract mucosal secretions, and is bi-directionally trafficked across epithelia by the neonatal Fc receptor (FcRn). Using physiologically relevant pH-polarized epididymal epithelia grown on Transwells®, IgG specifically targeting an extracellular chlamydial antigen; the Major Outer Membrane Protein (MOMP), enhanced uptake and translocation of infection at pH 6-6.5 but not at neutral pH. This was dependent on FcRn expression. Conversely, FcRn-mediated transport of IgG targeting the intracellular chlamydial inclusion membrane protein A (IncA), induced aberrant inclusion morphology, recruited autophagic proteins independent of lysosomes, and significantly reduced infection. Challenge of female mice with MOMP-specific IgG-opsonized C. muridarum delayed infection clearance but exacerbated oviduct occlusion. In male mice, MOMP-IgG elicited by immunization afforded no protection against testicular chlamydial infection, whereas; the transcytosis of IncA-IgG significantly reduced testicular chlamydial burden. Together these data show that the protective and pathological effects of IgG are dependent on FcRn-mediated transport as well as the specificity of IgG for intracellular or extracellular antigens.

Allergen capture by IgE and IgG enhanced cell-binding by allergen multimers: How complex is it?

Allergic diseases are the most common chronic disease of the western world, costing $7.8 billion per year in lost productivity and medical care in Australia alone.1 IgE is central to the immunopathogenesis of allergic diseases and important advances are now being made on multiple fronts of IgE research. In particular, two groups independently invested in the generation of IgE reporter mice to address the vexing question of the route of development of the elusive IgE+ B cell.2, 3 Two new anti-IgE mAb targeting membrane IgE and cell-bound IgE have the potential to deplete the cellular source of IgE.4, 5 These could be candidates for alternative anti-IgE treatment options with advantages over current anti-IgE therapy (OmalizumAb), which depletes free serum IgE. Researchers are still intrigued by the modes of interaction of IgE with allergen, and with both its receptors; the high affinity FcεR1 on mast cells and basophils, and the low affinity, C-type lectin, IgE receptor, CD23,6 on B cells and monocytes (Figure 1a and b). A new approach to the study of the complexity of these interactions was recently reported by Reginald et al.7 on page 167 of this issue.

DC-SIGN and alpha 2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human dendritic cells

Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases. Several mutually nonexclusive mechanisms are proposed to explain the beneficial effects of IVIg in patients (1, 2). Lately, Ravetch and colleagues (3) demonstrate that anti-inflammatory activity of IVIg is mediated mainly by antibodies that contain terminal _2,6-sialic acid linkages at the Asn297-linked glycan of Fc region.

Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia

Anti-factor VIII (FVIII) inhibitory IgG may arise as alloantibodies to therapeutic FVIII in patients with congenital hemophilia A, or as autoantibodies to endogenous FVIII in individuals with acquired hemophilia. We have described FVIII-hydrolyzing IgG both in hemophilia A patients with anti-FVIII IgG and in acquired hemophilia patients. Here, we compared the properties of proteolytic auto- and allo-antibodies. Rates of FVIII hydrolysis differed significantly between the two groups of antibodies. Proline-phenylalanine-arginine-methylcoumarinamide was a surrogate substrate for FVIII-hydrolyzing autoantibodies. Our data suggest that populations of proteolytic anti-FVIII IgG in acquired hemophilia patients are different from that of inhibitor-positive hemophilia A patients.

Induction of allergen-specific IgE and IgG responses by anti-idiotypic antibodies

In order to explore idiotypic, anti-idiotypic, and anti-anti-idiotypic responses to allergens, BALB/c mice were immunized with affinity- purified human idiotypic antibodies directed against a highly purified shrimp allergen. This resulted in the production of anti-idiotypic antibodies which were quantitated by using rabbit idiotypic antibodies raised against the same purified allergen. The mouse anti-idiotypic antibodies recognized shrimp-specific human idiotypic antibodies of the IgE isotype from 18 of 20 individuals, and IgG antibodies from 14 of 20 shrimp-sensitive patients. Immunization of BALB/c mice with affinity- purified, allergen-specific anti-idiotypic antibodies induced anti- allergen IgE and IgG responses in the absence of the allergen. This paper thus presents evidence that anti-idiotypic antibodies raised against allergen-specific idiotypic antibodies may substitute for the original allergen in the induction of allergen-specific idiotypic antibodies. The demonstration of shared idiotopes on IgG and IgE antibodies in the sera of shrimp-sensitive patients supports the use of allergen-specific anti-idiotypic antibodies as surrogate allergens.

Detection of IgG, IgA, IgM and IgE Antibodies in Invasive Amoebiasis in Endemic Areas

Entamoeba histolytica-specific serum IgG, IgA, IgM and IgE antibodies were assayed in cases of amoebiasis in an endemic area. Patient groups consisted of amoebic liver abscess (n=18), pre-abscess hepatic amoebiasis (n=22) and amoebic colitis (n=30). Control subjects comprised 26 asymptomatic cyst passers, 13 giardiasis cases, 20 typhoid patients and 24 non-amoebic individuals. Serum IgG was assayed by ELISA, using a monoclonal anti IgG β- galactosidase (IgG β-gal) conjugate, a polyclonal avidin biotin horse radish peroxidase (AB-HRP), and a polyclonal anti IgG horse radish peroxidase (IgG HRP) conjugate. IgA and IgM were assayed by the β-gal ELISA and IgE by AB-HRP. Diagnostically significant IgG and IgA while lower IgM and IgE antibody levels were seen in extraintestinal cases. About 40% of suspected pre-abscess hepatic amoebiasis cases were confirmed by antibody estimation. All isotype levels in most dysentery cases were in the range of the controls.

抗 LDH－C4 IgA 和IgG 抗体在粘膜免疫系统的分布及其抗生育作用的研究

已有的研究表明，小鼠背部携带能分泌抗原特异的IgA 单克隆抗体的杂交细 胞瘤，可以保护小鼠抵抗微生物和病毒等多种病原体经粘膜途径感染机体。我们 利用背部携带能分泌抗精子特异抗原（LDH-C4）的IgA 和IgG 杂交细胞瘤、以 及抗DNP 的IgA 骨髓细胞瘤的小鼠为动物模型，采用定量ELISA 法研究了抗 LDH－C4 IgA 与抗DNP IgA 单克隆抗体在呼吸道、肠道及生殖道内转运和分布， 抗LDH-C4 IgG2b 在肠道内转运与分布，以及抗LDH-C4 IgA 和IgG 单克隆抗体 在体内抗生育作用。 研究结果表明，带瘤小鼠血液中含有较高水平抗原特异的 IgA 和IgG 单克 隆抗体。PA4 和MOPC IgA 单克隆抗体在呼吸道、肠道以及雌性生殖道分泌物 内有较高的分布水平。在肠道，PA4 和MOPC IgA 单克隆抗体的分布水平显著 高于IgG（p<0.01 和p<0.05）。在肠道和生殖道的不同部位，IgA 抗体的分布水 平不同。在肠道，结肠分泌物中的IgA 单克隆抗体显著高于其它肠道部位 （p<0.01）。在生殖道，IgA 单克隆抗体分布水平以子宫角分泌物中最高。雄性 的前列腺也有较高的IgA 抗体水平。在呼吸道、肠道以及雌性生殖道相应部位的 分泌物内，PA4 IgA 单克隆抗体的水平显著高于MOPC IgA 单克隆抗体的分布水 平（p<0.05）。PA4 和MOPC IgA 单克隆抗体在粘膜分泌物内的分布水平差异可 能与其IgA 聚合形式的不同有关。另外，除气管外，在两时间点间分泌物中的 IgA 抗体水平没有显著差异。 检测背部带瘤小鼠交配后的两细胞胚胎期，发现携带PA4 和G2b 杂交细瘤 的雌性小鼠的受精率与对照组并没有显著的差异，这表明抗LDH-C4 IgA 和IgG 单克隆抗体在体内不能明显抑制小鼠的精子和卵子的结合或受精过程。注射细 胞后的27 天，检测鼠着床胚胎时，发现带瘤两性小鼠均携带PA4 时或者只有 雌性携带PA4 杂交瘤时，以及雌雄两性小鼠均携带G2b 杂交瘤细胞时，交配后的怀孕率与能分泌抗DNP 抗体的MOPC 的骨髓瘤细胞瘤的相应组别相比，显 著降低（p<0.01）。但PA4 各组与G2b 各组之间无显著差异(p>0.05）。然而，雌 雄的小鼠均带瘤时，最高怀孕减少率未能达100%。这些结果提示，抗LDHC4 IgA 和IgG 单克隆抗体在小鼠体内不能有效地抑制小鼠的精子与卵子的结 合，但能显著地抑制小鼠受精后胚胎的发育。抗LDH-C4 的IgA 和IgG 单克隆 抗体单独存在时，在体内均具有抗生育作用，但不能完全抑制生育。

抗LDH-C4 IgA和IgG抗体在带瘤小鼠生殖道和其它粘膜分泌物内分布特性的研究

中文摘要 　 已有的研究表明，小鼠背部携带能分泌抗原特异的IgA单克隆抗体的杂交细胞瘤，可以保护小鼠抵抗微生物和病毒等多种病原体经粘膜途径感染机体。我们利用背部携带能分泌抗精子特异抗原（LDH-C4）的IgA和IgG杂交细胞瘤、以及抗DNP的IgA骨髓细胞瘤的小鼠为动物模型，采用定量ELISA法研究了抗LDH-C4 IgA与抗DNP IgA单克隆抗体在呼吸道、肠道及生殖道内转运和分布，抗LDH-C4 IgG2b在肠道内转运和分布，以及抗LDH-C4 IgA和IgG单克隆抗体与体内抗生育作用的关系。研究结果表明，带瘤小鼠血液中含有较高水平抗原特异的IgA和IgG单克隆抗体。PA4和MOPC IgA单克隆抗体在呼吸道、肠道以及雌性生殖道分泌物内有较高的分布水平。在肠道，PA4和MOPC IgA 单克隆抗体的分布水平显著高于IgG（p < 0.01和p < 0.05）。在肠道和生殖道的不同部位，IgA抗体的分布水平不同。在肠道，结肠分泌物中的IgA单克隆抗体显著高于其它肠道部位（p < 0.01）。在生殖道，IgA单克隆抗体分布水平以子宫角分泌物中最高。雄性的前列腺也有较高的IgA抗体水平。在呼吸道、肠道以及雌性生殖道相应部位的分泌物内，PA4 IgA单克隆抗体的水平显著高于MOPC IgA单克隆抗体的分布水平（<0.05）。PA4和MOPC IgA单克隆抗体在粘膜分泌物内的分布水平差异可能与其IgA聚合形式的不同有关。另外，除气管外，在两时间点间分泌物中的IgA抗体水平没有显著差异。检测背部带瘤小鼠交配后的两细胞胚胎期，发现携带PA4或G2b杂交细胞瘤的雌雄小鼠的受精率与对照组并没有显著性差异，这表明抗LDH-C4 IgA和IgG单克隆抗体在体内不能显著抑制小鼠的精子和卵子的结合或受精过程。注射细胞后的27天，检测着床胚胎时，发现带瘤两性小鼠均携带PA4时或者只有雌性携带PA4杂交瘤时，以及雌雄性小鼠均携带G2b杂交瘤时，交配后的怀孕率与带能分泌抗DNP抗体的MOPC骨髓瘤细胞瘤的相应组别相比，显著降低（p < 0.01）。但PA4各组与G2b各组之间无显著差异（p < 0.05）。然而，雌雄小鼠均带瘤时，最高怀孕减少率也未达到100%。这些结果提示，抗LDH-C4 IgA和IgG单克隆抗体在小鼠体内不能有效地抑制小鼠的精子和卵子的结合，但能显著地抑制小鼠受精后胚胎的发育。抗LDH-C4 的IgA或者IgG单克隆抗体单独存在时，在小鼠体内均具有抗生育作用，但不能完全抑制生育。

Amplified immunoassay of human IgG using real-time biomolecular interaction analysis (BIA) technology

An automated biomolecular interaction analysis instrument (BI-Acore) based on surface plasmon resonance (SPR) has been used to determine human immunoglobulin G (IgG) in real time. Polyclonal anti-human IgG antibody was covalently immobilized to a carboxymethyldextran modified gold film surface. The samples of human IgG prepared in HBS buffer were poured over the immobilized surface. The signal amplification antibody was applied to amplify the response signal. After each measurement, the surface was regenerated with 0.1 mol/L H3PO4. The assay was rapid, requiring only 30 min for antibody immobilization and 20 min for each subsequent process of immune binding, antibody amplification and regeneration. The antibody immobilized surface had good response to human IgG in the range of 0.12-60 nmol/L with a detection limit of 60 pmol/L. The same antibody immobilized surface could be used for more than 110 cycles of binding, amplification and regeneration. The results demonstrate that the sensitivity, specificity and reproducibility of amplified immunoassay using real-time BIA technology are satisfactory.

口服牦牛血清IgG对小鼠免疫功能的影响

用环磷酰胺（Cy）制造小鼠免疫功能抑制模型，以口服扶正女贞素片的小鼠为阳性对照组，试验组小鼠连续口服耗牛血清IgG，10d后测定小鼠免疫水平的变化。结果，口服牦牛血清IgG的小鼠，抗Cy引起的免疫器官萎缩效果极显著（P＜0．01），抗Cy引起的小鼠血清IgG含量降低（P＜0．05），能提高小鼠血清IgG水平（P＜0．05）；牦牛血清IgG对小鼠急性毒性试验属无毒级。证明口服牦牛血清IgG能显著提高小鼠的免疫功能。

Selective defect of anti-pneumococcal IgG in a patient with persistent polyclonal B cell lymphocytosis.

BACKGROUND: Persistent polyclonal B cell lymphocytosis (PPBL) is a rare condition characterized by increased IgM and large excess of B cells with an IgD(+) CD27(+) phenotype. In normal individuals, these cells play a central role in the defense against pneumococcal infection. So far, few studies have characterized humoral immune responses in PPBL patients. We therefore measured IgG directed against S. pneumoniae antigens in a 51 yr-old woman with PPBL before and after vaccination with a pneumococcal 23-valent polysaccharide vaccine. METHODS: Antibodies against pneumococcal antigens were measured first with an overall immunoassay using microplates coated with the 23-valent pneumococcal vaccine. A serotype-specific test was also performed according to the WHO consensus protocol. RESULTS: Despite a large number of IgD(+) CD27(+) cells, our patient had low baseline titers of IgG directed against pneumococcal antigens and did not significantly respond to a 23-valent polysaccharide vaccine against S. pneumoniae. On the contrary, she had good titers of IgG directed against tetanus toxoid. CONCLUSION: IgM(+) IgD(+) CD27(+) cells which accumulate in this patient with typical PPBL patient failed to perform IgG isotype switch after a polysaccharide vaccine. The potential mechanisms and relationships with the main features of PPBL are discussed. Further studies on a larger number of similar patients are needed.