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PubMedDate not supplied

The molecular biology of immunoglobulin D.

Immunoglobulin D (IgD) is co-expressed with immunoglobulin M (IgM) on the membranes of most B cells, yet its biological function has remained a mystery. Recent detailed information on the structure and transcription of the unusual IgD heavy chain (delta) gene in mouse suggests a complex genetic control. A model is presented for the developmental regulation of IgM and IgD and roles suggested for the membrane and secreted forms of IgD in the immune network.

Animals↗
PubMed1998

Anti-D immunoglobulin in Rh(D) negative volunteers: clearance of Rh(D) positive red cells and kinetics of serum anti-D levels.

Properties of a new anti-D immunoglobulin were assessed in Rh(D) negative healthy male adults. Six volunteers received intravenous, and five volunteers intramuscular injections of 200 micrograms anti-D, 48 hours after pre-treatment with 5 mL of Rh(D) positive erythrocytes. Immediately after intravenous administration of anti-D, a rapid decrease of the Rh(D) positive erythroyctes was noted. After intramuscular injection of anti-D, there was a lag phase of 6 hours until the erythrocytes decreased, and the elimination rate was slower. Twenty-four hours after injection of anti-D, the Rh(D) positive erythrocytes were at the detection limit or no longer detectable in all volunteers. After intravenous administration, anti-D serum levels decreased from 45 ng/mL at 2 hours to 29 ng/mL at 24 hours, whereas after intramuscular administration, anti-D became detectable at 4 hours and increased to 11 ng/mL at 24 hours. During subsequent months, anti-D serum levels decreased at similar rates in both groups. After six months, anti-D was not detectable in any of the volunteers. Thus, the new anti-D immunoglobulin induced elimination of the Rh(D) positive erythrocytes and suggested that Rh(D) immunization of the volunteers was prevented.

Adult↗
PubMed2006

Molecular characterization of immunoglobulin D in mammals: immunoglobulin heavy constant delta genes in dogs, chimpanzees and four old world monkey species.

Antibodies are adaptor molecules that neutralize pathogens and link humoral and cellular defence mechanisms. Immunoglobulin D (IgD), one of the five antibody classes present in mammals, is expressed as an antigen receptor on naïve B cells. The functional role that IgD plays in the immune response is still poorly understood, but the recent characterization of immunoglobulin heavy constant delta genes (IGHD) in a variety of species challenges the view that IgD is of minor importance and is not present in many animals. On the basis of serological studies, IgD appears to be expressed in the majority of mammalian species examined. To confirm, at the molecular level, that IgD is present in different species, we cloned and sequenced IGHD cDNA from dogs and five non-human primate species (chimpanzee, rhesus macaque, cynomolgus macaque, baboon and sooty mangabey). Our results show that in all six species, IgD heavy chains possess three immunoglobulin domains and a long hinge region encoded by two exons. Only the hinge region of non-human primates is similar to the human hinge region, with conservation of O-glycosylation sites and multiple charged residues at opposing ends. The preservation of IgD in primates, dogs and previously characterized species suggests an important functional role for IgD, possibly involving binding to a receptor. The high degree of similarity existing between the structural features of human and non-human primate IgD suggests that non-human primates are suitable for in vivo studies designed to define the role that IgD plays in the immune response.

Amino Acid Sequence↗
PubMed1984

Antenatal prophylaxis of Rh immunization with 250 micrograms anti-D immunoglobulin.

Anti-D immunoglobulin (250 micrograms) was given i.m. to 830 Rh-negative primigravidae and multigravidae round the 32nd to 34th week of gestation. The multigravidae had previously been treated with anti-D immunoglobulin post partum or after abortion and had been followed up serologically after 8 months. Five hundred and twenty-nine of the women delivered Rh-positive infants and received another injection of anti-D immunoglobulin (250 micrograms) within 72 hours of delivery. At the serological follow-up 8 months after delivery 2 women (0.4%) had weak anti-D antibodies by the papain technique. No anti-D could be detected in these 2 women 14 and 20 months, respectively, after delivery. In a previously performed postnatal clinical study with 250 micrograms anti-D immunoglobulin the failure rate was 1.6% (10 out of 645 women). Thus, antenatal prophylaxis significantly (p less than 0.05) reduced the incidence of Rh immunization. The haemoglobin and bilirubin levels in cord blood and capillary blood did not differ in the Rh-positive and Rh-negative infants. Three primiparae (0.2%) had anti-D antibodies at the time of the antenatal injection before delivery. Thus, the antenatal regimen of gestation did not give full protection from Rh immunization. It is suggested that an antenatal injection at the 28th week of gestation would have been more effective, as Rh sensitization during pregnancy has been reported to be more frequent from the 29th week of pregnancy. Since the introduction of postnatal anti-D prophylaxis the Rh immunization occurring during pregnancy accounts for most of the observed failures (2, 4, 5, 14, 20). The efficacy and safety of antenatal injection of anti-D immunoglobulin has therefore been investigated (5, 6, 7). At the Växjö Hospital in Sweden, where the incidence of anti-D antibodies was 1.6% (15), 250 micrograms of anti-D immunoglobulin were given at about 32-34 weeks of gestation from March, 1973, to December, 1977. The results are presented here.

Antibodies↗
PubMed1991

IgD receptors on murine T-helper cells bind to Fd and Fc regions of immunoglobulin D.

Receptors for immunoglobulins on animal cells invariably show specificity for Fc regions of the protein and are hence called Fc receptors. The present study shows that immunoglobulin D receptors present an exception to this rule. Binding of IgD-coated erythrocytes to murine IgD-receptor-bearing T-helper cells is competitively inhibited by IgD, by its Fab delta fragments, and by deletion mutants of IgD lacking (i) the first constant domain of the delta heavy chain (KWD1), (ii) that region plus the delta heavy-chain-hinge region (KWD6), or (iii) the third constant domain of the delta heavy chain (Gen. 24). KWD1, Gen. 24, or KWD6 mutants bind to T-helper cells bearing receptors for IgD independently of each other. Furthermore, Gen. 24 and KWD6 mutants also competitively inhibit binding of each other in cross-blocking experiments. These results show that the IgD receptors binds to the Fd delta and the Fc delta and cannot readily be explained by sequence homology between the two parts of the IgD molecule.

Amino Acid Sequence↗
PubMed2000

Audit of anti-D immunoglobulin administration to pregnant Rhesus D negative women following sensitising events.

We performed a retrospective audit of 99 Rhesus D (RhD) negative women to discover if anti-D immunoglobulin (anti-D) prophylaxis was given in accordance with guidelines from the National Blood Transfusion Service Immunoglobulin Working Party (1991). It was found that all patients received appropriate management postpartum. However, more than half of the antepartum sensitising events beyond 20 weeks' gestation were not managed according to the guidelines. Only one patient was sensitised during the studied pregnancy and no sensitising events were recorded in her case. This supports the introduction of a policy of routine anti-D prophylaxis in the third trimester.

Journal Article↗
PubMed1988

[Hepatitis non-A, non-B-associated DNA--demonstration of DNA in proven infectious anti-D-immunoglobulin].

An anti-D-immunoglobulin preparation implicated in a hepatitis non-A,non-B transmission was analyzed for the presence of a DNA, which was originally isolated, cloned and sequenced from feces of a patient with posttransfusion HNANB. The investigation was performed by a DNA polymerase chain reaction using synthetic oligoprimers. Commercially available immunoglobulin preparations served as controls. The demonstration of identical DNA sequences in the infectious material speaks in favour of this up to now unknown circular and partially double-stranded DNA to be a virus genome involved in hepatitis non-A,non-B.

Antibodies, Anti-Idiotypic↗
PubMed1987

Immunoglobulin D in cerebrospinal fluid.

Immunoglobulin D (IgD) was measured by radioimmunoassay in paired cerebrospinal fluid and serum samples from patients with various neurological diseases. The IgD index was calculated for every patient and compared with the IgG index. An increased IgD index was found in 18 out of 41 patients suffering from multiple sclerosis and in 52 out of all 122 patients investigated. An increased IgD index did not always coincide with an increased IgG index. An increased IgD index suggests an abnormal intrathecal synthesis of this immunoglobulin within the central nervous system. We conclude that the determination of IgD in the cerebrospinal fluid yields additional information on immunological reactions within the central nervous system.

Humans↗
PubMedDate not supplied

A follow-up study of 49 adult patients with idiopathic thrombocytopenic purpura treated with high-dose immunoglobulins and anti-D immunoglobulins.

BACKGROUND: We analyze here short- and long-term results in 49 patients with idiopathic thrombocytopenic purpura (ITP), consecutively treated with high-dose (h.d.) immunoglobulins (Ig) or anti-D Ig. The major aims of this study were to assess the prognostic power of some patient characteristics and to verify the possibility that repeated courses of treatment can induce a stable remission. Moreover, the relative efficacy and safety of these two treatments were compared. PATIENTS AND METHODS: Group A included 28 patients with chronic ITP and 17 with ITP of recent onset who were receiving h.d. Ig; Group B included 5 patients with ITP of recent onset and 7 with chronic ITP treated with anti-D Ig. Eight cases, receiving both treatment, were included in both groups. Response to treatment was defined as any increase in platelet count above 30 x 10(9)/l, when the platelet count was less than 10 x 10(9)/l, or any doubling of the basal platelet count otherwise. Remission was defined as any platelet count higher than 100 x 10(9)/l lasting for 3 months or longer without therapy. RESULTS AND CONCLUSIONS: Cumulative response and remission rate was not statistically different in the two groups. Multivariate logistic regression analysis showed no influence of sex, previous therapy or duration of disease. Patients older than 60 years were definitely less responsive to h.d. Ig (58% vs 92%, p = 0.03). In Group A, two patients obtained remission after the first course of h.d. Ig. No additional remissions were obtained by repeated courses of h.d. Ig, apart from a single case of ITP of recent onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

The Yorkshire antenatal anti-D immunoglobulin trial in primigravidae.

2069 Rh(D)-negative women in their first pregnancy received 100 micrograms doses of anti-D immunoglobulin at 28 and 34 weeks' gestation and a further dose at delivery if the infant was Rh(D)-positive. The antibody status was determined at 28 weeks, 34 weeks, at delivery, and 6 months after delivery. The findings were compared with those in a control group of 2000 Rh(D)-negative primigravidae who gave birth to Rh(D)-positive infants and received the standard post-delivery injection of anti-D immunoglobulin. 2 women in the trial group and 18 in the control group became actively immunised during the first pregnancy. 325 women in the trial group have had a further Rh(D)-positive pregnancy and in 2 anti-D antibodies were detected for the first time. 528 control women have had a further Rh(D)-positive pregnancy and anti-D was demonstrable in 29-18 in whom antibodies developed during the first pregnancy and 11 in whom antibodies first appeared during the second. The reduction in the incidence of sensitisation was significant. It is estimated that the extra cost in anti-D immunoglobulin was approximately pounds 1600 for each woman sensitised.

Clinical Trials as Topic↗