High-dose intravenous immunoglobulin therapy improved muscle strength in a patient with multifocal motor neuropathy and antibodies against the glycolipid LK1

We report improvement in muscle strength in a patient with multifocal motor neuropathy (MMN) when given high-dose intravenous immunoglobin (i.v.-Ig) treatment. The patient had asymmetrical limb weakness, atrophy and absent or weak reflexes, but no sensory disturbances. Neurography showed multiple conduction blocks in peripheral motor nerves but no sensory nerve abnormalities. Serum and anti-GM1 antibodies were not found, however, the patient had serum antibodies against the glycolipid LK1, an epitope found both in glycolipid and also in some glycoproteins in peripheral nerve myelin. Muscle strength improved 5 days after i.v.-Ig therapy, and lasted about 10 weeks. Repeated courses of treatment resulted in similar improvement. This is, to our knowledge, the first patient reported with MMN found to have antibodies against the glycolipid LK1.     

Immunoglobulin Y Levels in Egg Yolk From Three Chicken Genotypes

Laying hens are very efficient producers of antibodies and provide an interesting alternative for large-scale production of specific antibodies. These antibodies also have biochemical advantages over mammalian antibodies (e.g. rabbit antibodies) that can be used to improve immunoassays where antibodies are used. The concentration of IgY in egg yolk is an important production parameter. The purpose of this study was to investigate the genetic variation of IgY levels in egg yolk. We have compared IgY concentrations in egg yolks from two lines, selected for egg production traits at the Swedish University for Agricultural Sciences (Single Comb White Leghorn and Rhode Island Red) and a cross between the two lines (SLU-1392). Single Comb White Leghorns have the highest mean concentration of yolk IgY, 2.21 mg ml^-1 compared to SLU-1392 1.95 mg ml^-1 and Rhode Island Red 1.68 mg ml^-1. The cross thus had an intermediate IgY concentration in relation two the two other lines. There were great differences between individual animals within each line. Our results indicate that it should be possible to increase yolk antibody production by using a high producing chicken line and by genetic selection within the line. We found three individuals with very low yolk IgY concentrations among the Rhode Island Red hens. Newly hatched chickens with limited amounts of IgY from the hen may be more susceptible to infections.     

Suppression of B cell differentiation by ligation of membrane-bound IgM

Using B cells from the transgenic mouse line B6-Sp6 and control littermates, stimulated by lipopolysaccharide (LPS) under novel culture conditions that provide for the response of all B cells, we show here that specific ligation of the surface IgM molecules always results in inhibition of terminal differentiation and immunoglobulin secretion by activated cells, regardless of the ligand. Thus, monoclonal antibodies to (a) the CH region of Ig (anti-μ. and anti-allotype), (b) the Cx region, (c) the V region (anti-idiotype) of surface IgM, as well as (d) multivalent antigen (2,4,6-trinitrophenyl-bovine serum albumin), all show similar effects and dose-response curves. IgD-negative transgenic B cells are equally sensitive to IgM ligation-dependent inhibition, as control (IgD-positive) B cells. The allotype specificity of this inhibition, assessed by using anti-u, allotype reagents to inhibit and assay the responses, suggests that B cells expressing transgenic or endogenous IgM in transgenic B6-Sp6 mice are largely independent populations. These observations establish that anti-IgM antibodies in conjunction with appropriate LPS stimulation, provide a universal model system for functional characterization of B cell responses.     

Chronic anemia as a complication of parvovirus B19 infection in a pediatric kidney transplant patient

. This is a report of unexplained anemia that persisted for 4 months in an adolescent renal transplant patient receiving immunosuppression that included prednisone, tacrolimus, and mycophenolate mofetil. This patient required monthly blood transfusions for fatigue, palpitations, and hematocrit levels between 15% and 17%. In addition, his posttransplant course was notable for the development of insulin-dependent diabetes mellitus. While receiving low-dose prednisone, he was switched from tacrolimus to cyclosporin and tapered off insulin injections over the next 2 months. At 4.5 months post-transplantation, further diagnostic evaluation was suggestive of parvovirus B19 infection as the cause for our patient’s chronic anemia. After testing negative for serum-specific parvovirus B19 IgM and IgG antibodies, parvovirus B19 infection was detected in blood by the polymerase chain reaction. Treatment with intravenous immunoglobulin (1 g/kg per day × 2 days) resulted in normalization of both his reticulocyte count and hematocrit within 6 weeks. At 4 months after receiving the immunoglobulin infusion, he has maintained a normal hematocrit level and stable renal function without requiring further blood transfusions. Received August 23, 1996; received in revised form and accepted November 20, 1996     

Interactions between membrane IgM and the cytoskeleton involve the cytoplasmic domain of the immunoglobulin receptor

Cross-linking induced interactions between the membrane form of immunoglobulin (mIg) and the cytoskeletal matrix have been described by several groups. To date, the function of mIgM association with the cytoskeleton is not yet understood. Delineation of the molecular basis of these interactions will be instrumental in elucidating their function. We have previously shown that the Igα/β heterodimer is not required for ligand-induced mIgM binding to the cytoskeleton. In this study, we have investigated the role of other B cell-specific proteins in mediating these interactions. For this, we expressed mIgM in the non-hematopoietic human cervical carcinoma cell line HeLa S3 and verified the capacity of the surface-expressed IgM to interact with the cytoskeletal matrix upon cross-linking with anti-μ chain antibodies. We show here that only the mIgM molecule itself and no other B cell-specific protein(s) is required in mediating mIgM interactions with actin filaments. In an attempt to determine the cytoskeleton-binding site of mIgM we investigated the role of the cytoplasmic tail of mIgM (KVK) in binding the receptor to actin-based microfilaments. Using mutated forms of mIgM expressed in J558L cells, we show here that KVK plays a role in mediating these interactions. The absence of KVK did not, however, completely abrogate mIgM-cytoskeletal interactions, suggesting that there are additional molecular requirements for the ligand-induced mIgM binding to the cytoskeletal matrix.     

GM1, a ganglioside that specifically enhances immunoglobulin production and proliferation in human plasma cells

The effects of gangliosides on human plasma cell responses were studied. Among the various gangliosides tested, only GM1 enhanced immunoglobulin (Ig) production and proliferation in the human plasma cell lines, IM-9 and AF-10, while other gangliosides (GM2, GM3, GD1a, GD1b, GD3, GT1b, and GQ1b) had no effect. Among the various cytokines tested, including interleukin (IL)-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, interferon (IFN)-α and IFN-γ, only IL-6 enhanced Ig production and proliferation in IM-9 and AF-10 cells. However, the enhancement of plasma cell responses by GM1 was specific and was not mediated by IL-6, since GM1 activity was blocked by anti-GM1 monoclonal antibody (mAb), but not by control IgM, anti-IL-6 Ab or the anti-IL-6 receptor mAb, PM1. Conversely, the enhancement by IL-6 was blocked by anti-IL-6 Ab and PM1, but not by anti-GM1 mAb. GM1, but not other gangliosides, also enhanced Ig production and proliferation in freshly separated plasma cells from patients with plasma cell leukemia and in plasma cells generated in vitro. These actions of GM1 were specifically blocked by anti-GM1 mAb, but not by anti-IL-6 Ab or PM1. These results indicate that GM1 may be an important regulator of plasma cell responses.     

Cloning of a human immunoglobulin gene fragment containing both VH-D and D-JH rearrangements: Implication for VH-D as an intermediate to VH-D-JH formation

In an Epstein-Barr virus-transformed human B cell line we found an unusual immunoglobulin heavy chain gene rearrangement. Restriction mapping and sequencing analysis led us to conclude that V_H-D and D-J_H recombination took place in a single allele. Both V_H-D and D-J_H complexes still had their recombination signal sequences adjacent and the DNA sandwiched by these two complexes retained a germ line configuration, suggesting the potential for a secondary rearrangement resulting in a V_H-D(-D)-J_H formation. With this finding, we propose a novel pathway, in which the V_H-D complex is an intermediate in the formation of a functional V_H exon.     

Increased monocyte-dependent suppression of polyclonal activation of B lymphocytes from cystinotic children

In infantile cystinosis the amino acid cystine preferentially accumulates in phagocytic cells, polymorphonuclear leucocytes (PMN) and monocytes, rather than in lymphocytes. We previously described functional abnormalities in the oxidative metabolism and locomotion of cystinotic PMN and monocytes. The present study shows an abnormal lymphocyte polyclonal activation as evidenced by a decreased immunoglobulin (Ig) production and generation of Ig-containing cells (ICC) in cultures of peripheral blood mononuclear cells (PBMC) from cystinotic children upon stimultion with pokeweed mitogen andStaphylococcus aureus Cowan I. However, monocyte depletion from cystinotic PBMC fully reconstituted Ig production and ICC generation, indicating: (1) the presence of an increased monocyte-dependent suppression on lymphocyte polyclonal activation, and (2) that the intrinsic ability of cystinotic lymphocytes to respond to polyclonal stimulation was preserved. The increased cystinotic monocytedependent suppressive effect was not mediated by prostaglandin E₂ (PGE₂) since its production by cystinotic PBMC upon polyclonal activation was not different from that of controls. In addition, the sensitivity of cystinotic lymphocytes to the immunosuppressive effect of varying concentrations of exogenous PGE₂ was similar to that of controls. Finally, indomethacin and 2-mercaptoethanol, two agents able to scavenge hydroxyl (OH) radicals, restored Ig production by cystinotic PBMC, suggesting a role for reactive oxygen species in the increased cystinotic monocyte-dependent suppression.     

母儿血型不合IgG抗体效价≥1：512是否提示胎儿病情严重

目的：探讨母儿血型不合IgG抗体效价≥1：512是否提示胎儿病情严重。方法：对6例血清IgG抗A（B）抗体效价≥1：512的母儿血型不合孕妇，进行羊膜腔穿刺抽样羊水作胆红素、IgG抗体效价和胎儿血型物质测定，抽取其新生儿脐血作胎儿血型、胆红素检测及Coombs试验。结果：孕妇血清IgG抗体效价与新生儿溶血病的严重程度并不密切相关。结论：不能单纯以孕妇血清抗体效价的高低作为判断胎儿溶血的唯一依据。     

Prevention of necrotizing enterocolitis in extremely low birth weight infants by IgG feeding?

Oral immunoglobulin has been described as preventing necrotizing enterocolitis(NEC) in preterm infants. To prevent NEC in extremely low birth weight infants (ELBW), we have carried out oral IgG prophylaxis since April 1991. The efficacy of this prophylaxis was examined in a study comparing historical cohorts. ELBW infants delivered in the Department of Obstetrics and Gynaecology of the University of Ulm and treated until day 28 in the level III intensive care nursery, Division of Neonatology, University of Ulm were included. Cohort 1, born between 1.1.1988 and 31.3.1991, received no oral IgG and served as a control [n=84, gestational age: median 26 weeks, range 24–34; birth weight: 811 g, 490–990], cohort 2, born between 1.4.1991 and 31.12.1995 [n=137, gestational age: 26 weeks, 22–32; birth weight: 760 g, 362–995], received 6 × 100 mg/kg human IgG (Beriglobin) orally on days 1–28. NEC, stage 2a and higher according to the modified classification of Bell, was observed in 9 of 84 (10.7%) infants of cohort 1 and in 11 of 137 (8%) infants of cohort 2 until day 28. The difference did not reach statistical significance (P=0.63 Fisher's exact test). Conclusion In this historical cohort study, ELBW infants were not protected against NEC by oral IgG. The present published evidence does not allow recommendation of oral human IgG administration in preterm infants as a prophylactic measure against NEC. Received: 8 June 1997 / Accepted in revised form: 1 January 1998