Appearance Of IgG Research Articles

Diagnostic Accuracy of LDBIO-Toxo II IgG and IgM Western Blot in Suspected Seroconversion in Pregnancy: A Multicentre Study.

The high sensitivity of the automated tests used for Toxoplasma gondii serology can yield false-positive IgM results due to aspecific reactions. On the other hand, specific therapy can delay IgG production and, therefore, the diagnosis of seroconversion. There is a need for confirmation tests to early detect seroconversions during pregnancy. We conducted a multicentre study to evaluate the diagnostic accuracy of the Toxo II IgG and a new, not yet commercialised Toxo II IgM western blot (WB) (LDBio diagnostics Lyon France) on 229 sera corresponding to 93 patients with seroconversions and 158 sera corresponding to 68 patients with nonspecific IgM. Sensitivity was 97.8% for IgM WB and 98.9% for IgG WB. Specificity was 89.7% and 100%, respectively. The concordance between IgM and IgG Toxo WB with the final diagnosis was very good, K = 0.89 and K = 0.99, respectively. In 5 cases (5.4%), the appearance of IgM, and in 55 cases (59.1%), the appearance of IgG was recorded by WB earlier than by traditional tests. In 10 cases (10.8%), IgM was detected after the traditional tests and in 2 cases (2.2%) for IgG. The association of IgG and IgM WB on the same sample not only detected all seroconversions but also correctly identified most of the false-positive results.

Production of SARS-CoV-2 Antibodies and Emergence of the Clinical Symptoms of COVID-19

Coronavirus disease 2019 (COVID-19) is a worldwide public health problem that has attracted much attention due to its clinical findings. Measurement of IgG and IgM antibodies is of great importance for researchers and it will help to develop a new diagnostic and therapeutic method in clinical care. In this cross-sectional study, we aim to measure the IgG and IgM antibody levels in 401 suspected COVID-19 volunteers. We also measure the time duration for the appearance of IgG and IgM antibodies from the onset of symptoms to sampling time. Of 401 participants enrolled in the study, 255 (63.59%) were healthy, 79 (19.70%) were a carrier, 59 (14.71%) were cured and 8 (1.99%) were borderline. Of 142 subjects diagnosed with COVID-19, 41 (28.87%) presented with gastrointestinal (GI) symptoms, 83 (58.45%) had no GI symptoms, and 18 (12.68%) were asymptomatic. According to our findings, the measurement of IgG and IgM antibodies will provide the tool for the diagnosis of COVID-19 and significantly boost research into novel diagnostic and therapeutic approaches.

Comparison of the clinical manifestations between different age groups of patients with overseas imported COVID-19.

The current study investigated the clinical manifestations and outcomes of different age groups of patients with overseas imported COVID-19. In total, 53 COVID-19 patients admitted to the designated Beijing Xiaotangshan Hospital between March 16 and April 15 of 2020 were included. Based on the percentage of disease aggravation during hospital stay according to CT, the patients were divided into two groups: ≤40 years (group A; n = 41) and >40 years (group B; n = 12). The demographic data, epidemiological history, disease courses, potential complications, clinical symptoms, lab indices, chest CT outcomes, treatment protocols and turnovers of the two groups were compared. According to clinical typing, compared with group A, group B had a significantly greater proportion of the common type of COVID-19 (P<0.05) and greater comorbidity of type 2 diabetes (P<0.001). The two groups presented significantly different lab indices. Group B showed significantly more frequent CT abnormalities, with greater proportions of multiple lesions and bilateral lung involvement (P<0.05). During hospitalization, group B had a greater proportion of disease aggravation according to CT (P<0.01). Compared with group A, group B received a significantly greater proportion of antiviral therapy and presented a significantly greater occurrence of adverse drug reactions (P<0.05). The two groups did not significantly differ in time from admission to clinical symptom improvement or from disease onset to negative outcomes according to nucleic acid testing, the appearance of IgG or the appearance of IgM. They also did not significantly differ in length of stay. Older imported COVID-19 patients, particularly those with type 2 diabetes, showed a broader pulmonary extent and faster development of the disease, more severe pathogenetic conditions and a greater risk of developing a critically severe type. Increased attention should be given to this population in clinical practice.

Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed “original antigenic sin.” The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.

Antibody response patterns in chikungunya febrile phase predict protection versus progression to chronic arthritis

Chikungunya virus (CHIKV) infection causes acute febrile illness in humans, and some of these individuals develop a debilitating chronic arthritis that can persist for months to years for reasons that remain poorly understood. In this study from India, we characterized antibody response patterns in febrile chikungunya patients and further assessed the association of these initial febrile-phase antibody response patterns with protection versus progression to developing chronic arthritis. We found 5 distinct patterns of the antibody responses in the febrile phase: no CHIKV binding or neutralizing (NT) antibodies but PCR positive, IgM alone with no NT activity, IgM alone with NT activity, IgM and IgG without NT activity, and IgM and IgG with NT activity. A 20-month follow-up showed that appearance of NT activity regardless of antibody isotype or appearance of IgG regardless of NT activity during the initial febrile phase was associated with a robust protection against developing chronic arthritis in the future. These findings, while providing potentially novel insights on correlates of protective immunity against chikungunya-induced chronic arthritis, suggest that qualitative differences in the antibody response patterns that have evolved during the febrile phase can serve as biomarkers that allow prediction of protection or progression to chronic arthritis in the future.

Continuous milking of dairy cows disrupts timing of peak IgG concentration appearance in mammary secretions.

The length of the dry period in commercial dairy production is under close scrutiny. While the main concern is the composition and volume of milk produced, the evaluation of colostrum quality under these new paradigms has suggested a decline in IgG concentrations, while some reports indicate no change. Colostrum quality has been defined as an adequate concentration (>50mg/ml) of immunoglobulin in the secretions to provide the newborn with maximal disease resistance. We investigated the appearance of IgG in mammary pre- and post partum secretions in cows without a dry period (continuously milked, Dry0) and compared the secretions with cows that experienced a dry period of 60d (Dry60). Blood was collected during the experimental period and plasma analysed for progesterone (P4) and prolactin (Prl). Approximately -6d relative to parturition, the Dry0 animals exhibited increased concentration of IgG in their secretions to an average of ∼35mg/ml that remained rather constant through subsequent pregnancy and following parturition. Dry0 cows were producing an average IgG concentration in parturition colostrum of 44·2±17·6mg/ml that was not different than that of controls (66·86±16·8mg/ml). However, Dry0 cows exhibited high variation, different peak times (day) of IgG concentration including times that occurred both pre and post parturition. IgG mass of the Dry0 cows remained rather constant pre- and post partum and did not show the same declining mass following parturition that was shown for the Dry60 cows. The change in plasma P4 and Prl were shown to have no timing effect on colostrum IgG concentration.

Utility of Immunoblotting for Early Diagnosis of Toxoplasmosis Seroconversion in Pregnant Women

Congenital transmission of Toxoplasma gondii occurs mainly when a mother acquires the infection for the first time during pregnancy. It was recently shown that although early treatment of the primary infection during pregnancy has little or no impact on the fetomaternal transmission rate, it does reduce the incidence of sequelae in infected infants. Seroconversion is defined by the appearance of IgG. Commercial reagents continue to vary considerably in detecting low concentrations of antibodies, as during early seroconversion. We compared two routinely used immunoassays (IA) (Platelia and Elecsys Toxo IgG) and an indirect immunofluorescence assay (IIF) with a qualitative test based on immunoblot analysis (Toxo II IgG) (IB) to assess their abilities to diagnose seroconversion at its earliest stages. This prospective study was carried out between January and November 2010. It included 39 pregnant women with monthly follow-up who seroconverted during pregnancy. On first sera that were IgM positive but IgG negative (or equivocal) as detected by IA, IB diagnosed seroconversion twice as often as IIF (26/39 [66.7%] versus 13/39 [33.3%]; P < 0.001; χ(2) test). Serum samples were retaken 2 to 5 weeks later for the other 13 cases (IgG negative by IB on first serum). Seroconversion was demonstrated as follows: IB for 5 cases where IA remained negative or equivocal, IB and IIF for 5 cases where IA remained negative or equivocal, IA for 2 cases, and no method for 1 case (a third sample was necessary). In summary, IB permitted toxoplasmosis seroconversion diagnosis before other means in 92.3% of cases (36/39) and thus earlier therapeutic intervention.

Transition from inflammatory to anti-inflammatory immune responses in deer mice infected with Sin Nombre virus (105.20)

Abstract Hantavirus cardiopulmonary syndrome (HCPS) is characterized by pronounced inflammation that is thought to contribute to its pathogenesis. Deer mice (Peromyscus maniculatus) are the principal reservoir hosts of Sin Nombre virus (SNV), the etiologic agent of the great majority of HCPS cases in North America. Deer mice have life-long apathogenic persistence with periods of viral shedding in excrement. Virus-specific CD4+ T cells from deer mice possess features of regulatory T cells at persistence. We examined the post-infection kinetics of viral load and immune gene expression in deer mice on days 2, 5, 7, 10, 15 and 20. Viral RNA peaked on day 10 in the lungs and day 15 in the heart, with decreased RNA correlating with the appearance of IgG on day 15. In spleens, Ccl3 and Ccl5 expression was elevated on day 2, while Ccl2 expression was elevated on days 7-15. Several inflammatory cytokine genes were elevated on days 5 and 7, including IL-12p35, IL-21 and IL-23, but then declined. TGFβ1 expression occurred early in infection, but markedly declined and reappeared on days 15 and 20. CD4 expression was elevated on day 7 while CD8 and TCRβ expression were elevated on days 7 and 10, perhaps reflecting a stalled antiviral T cell response. These data suggest that early in infection an inflammatory immune response occurs, but it transitions to an anti-inflammatory response. This switch may interfere with viral clearance and contribute to the persistence and ecology of SNV.

Sequential Intramolecular Epitope Spreading of Humoral Responses to Human BPAG2 in a Transgenic Model

Bullous pemphigoid (BP) is a subepidermal autoimmune disease characterized by a humoral response to an epidermal basement membrane (BM) component, BP antigen 2 (BPAG2). BP patients have IgG autoantibodies against an immunodominant BPAG2 extracellular domain termed NC16A as well as additional epitopes located both in the intracellular and extracellular domains (ICD and ECD, respectively) of this autoantigen. To study the evolution of humoral responses to BPAG2, sequential serum samples obtained from C57BL/6Ncr mice grafted with otherwise syngeneic skin from transgenic mice expressing human BPAG2 (hBPAG2) in epidermal BM were studied for IgG reactivity to seven ECD and ICD hBPAG2 epitopes. All grafted mice developed specific IgG against hBPAG2 ECD and ICD epitopes. In seven of eight mice, anti-hBPAG2 IgG was initially directed against ECD epitopes; in six mice, humoral responses subsequently targeted additional ECD and ICD BPAG2 epitopes. In contrast to IgG specific for ECD epitopes, IgG against ICD epitopes was present at lower levels, detectable for shorter periods, and non-complement fixing. Interestingly, the appearance of IgG directed against ICD epitopes correlated with the development of graft loss in this experimental model. These studies provide a comprehensive and prospective characterization of the evolution of humoral immune responses to hBPAG2 in vivo.

Expression of all six human Torque teno virus (TTV) proteins in bacteria and in insect cells, and analysis of their IgG responses

Torque teno virus (TTV) is a non-enveloped human virus with a circular (∼ 3800 nt) ssDNA genome. TTV transcription results in three viral mRNAs and six proteins, the function or antigenicity of which are unknown. The six open reading frames of TTV genotype 6 were expressed in bacteria and insect cells. Expression of the ORF1/1-encoded protein was inefficient, while expression of the others was successful, with ORF1 and ORF1/2 as arginine-rich region depleted. All six recombinant TTV proteins were antigenic. Of healthy adults, 11 / 25 (44%) showed strong IgG reactivity with one or more proteins. Four subjects, two of whom were genotype-6-DNA positive, were followed. One of the latter showed concurrently a strong IgG response against the ORF1 protein. The other showed appearance of IgG against the ORF2 protein concomitantly with resolution of the genotype-6 viremia. The genotype-6 sequences remained unaltered for years, suggesting that some mechanisms other than amino acid substitutions play a role in TTV immune evasion.

Kinetics of Immune Responses and Tumor Burden in Patients with Indolent B Cell Lymphomas Receiving Recombinant Idiotype Vaccination as the Sole Treatment.

Immunization of patients with B-cell non-Hodgkin's lymphoma with the individual idiotype expressed by the malignant clone can induce tumor-specific immune responses that correlate with improved remission duration and survival rates after cytoreductive chemotherapy. We have developed a production method for a recombinant idiotype vaccine based on expression of Fab fragments in E. coli. Intradermal administration of this vaccine mixed with lipid-based adjuvant and subcutaneous coadministration of GM-CSF has excellent immunogenicity as demonstrated by a high and idiotype-specific immune response rate in a phase I trial in advanced lymphoma patients with a severely impaired immune status (Bertinetti et al., Cancer Research 2006). Of a cohort of 15 patients with newly diagnosed or relapsed indolent B cell malignancies who had not been treated with conventional cytoreductive therapy and received 6 monthly immunizations of this idiotype vaccine, we observed 6 cases (40%) with objective quantitative evidence of tumor regression. 5 of these patients were in primary “watch and wait” situation for indolent NHL, and 1 follicular lymphoma patient had recurrence of nodal disease after a complete remission achieved in the phase I trial. At weeks 0, 8, 24, 36, and 52 after initiation of vaccination, staging examinations were performed including enumeration of circulating tumor cells by quantitative real-time PCR, and immune responses were assessed by ELISPOT and ELISA. Beginning with the 4th vaccination, evidence for reduction of nodal disase was noted in 5 cases, 4 of which achieved an objective partial response after all 6 scheduled immunizations according to standard staging criteria. These patients received continuing vaccinations in intervals of 1–3 months, and no progression has occurred after a follow-up of 9–32 months. Of 6 patients who had detectable lymphoma cells in the peripheral blood, 4 showed a continuous, at least 10fold decrease of the number of circulating lymphoma cells during the course of the vaccination. Two of the partial responders had never evidence for circulating tumor cells. A T cell response to the vaccine developed in 4/5 evaluated patients with evidence of tumor regression and in 3/6 patients without evidence for a clinical response. These cellular responses were maintained at stable levels during the vaccination and continued to be present 6 months after the last vaccination. Humoral immune responses were induced in 5/5 patients with declining tumor burden and in 2/6 non-responders. In 3 cases, the anti-idiotypic antibody titers declined after 6 months. In cases where anti-idiotype antibodies of IgM and IgG isotype occurred, IgM preceded the appearance of IgG. All objective clinical responders mounted a combined cellular and humoral immune response. The temporal association of immune responses with tumor regression provides support for the assumption that recombinant idiotype vaccination in the chosen format may play a causal role for a favorable disease course in previously untreated indolent lymphomas and may hence obviate the need for cytoreductive chemotherapy for extended time periods.

Breaking of tolerance to native DNA in nonautoimmune mice by immunization with natural protein/DNA complexes

A major event in the pathogenesis of systemic lupus erythematosus (SLE) is the breaking of tolerance to native DNA and the appearance of IgG anti-double-stranded (ds) DNA antibodies. The mechanisms of the losing of tolerance are not well understood. Continuous efforts have been made in the past to induce anti-native DNA IgG autoantibodies in non-autoimmune animals but the relevance of the approaches used to what happens in spontaneous disease is unclear. We succeeded in breaking tolerance to native DNA in nonautoimmune-prone BALB/c mice by immunization with natural DNA/protein complexes. These complexes included nucleosomes, crude commercial histone and nucleohistone preparations. The anti-dsDNA IgG response lasted for more than an year. IgG deposition in the kidneys of the animals was repeatedly shown. As DNA-specific B cells behave in many ways as non-autoreactive B cells, we suggest that the activity of the self-reactive B lymphocytes could be selectively inhibited in a way that mimics a physiological mechanism controlling the magnitude and duration of the IgG antibody response to foreign antigens.

Characterization of immunoglobulin gamma 1 from a monotreme, Tachyglossus aculeatus.

A full-length immunoglobulin gamma clone from the echidna (Tachyglossus aculeatus) was isolated from a spleen cDNA library. The clone was 1,664 base pairs long and encoded the entire open reading frame, incorporating the V, D, J and C regions. The echidna clone had approximately 41% identity and 67% similarity at the amino acid level with both marsupial and eutherian IgG molecules. The presence of IgG in the monotremes confirms that the appearance of IgG occurred prior to the separation of the three extant mammalian lineages, but after their separation from the reptilian lineage, pinpointing the date to between 310 and 170 million years ago. Phylogenetic analyses using the immunoglobulin sequence data strongly support the 'Theria' hypothesis, with the monotreme lineage diverging prior to the separation of the marsupial and eutherian lineages.

Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA.

Autoantibodies against cytochromes P-4502E1 and P-4503A in alcoholics.

Autoantibodies against soluble liver enzymes have been reported among alcoholics, but the targets of self-reactivity toward membrane proteins of the liver have not been characterized. Previously, among alcoholics, we found antibodies against ethanol-derived radical protein adducts that are dependent on cytochrome P-4502E1 (CYP2E1) for their formation. To further investigate autoantibodies against cytochrome P-450s during alcohol abuse, sera of rats chronically treated with ethanol in the total enteral nutrition model and sera from alcoholics with or without alcohol liver disease and from control subjects were analyzed by enzyme-linked immunosorbent assay and Western blotting for the presence of IgG against rat and human CYP2E1, rat CYP3A1, and human CYP3A4. A time-dependent appearance of IgG against rat CYP3A1 and CYP2E1 was evident during chronic ethanol feeding of rats. Anti-CYP2E1 reactivity showed positive correlation with the levels of hepatic CYP2E1 and was inhibited by the CYP2E1 transcriptional inhibitor chlormethiazole. Screening of the human sera by enzyme-linked immunosorbent assay revealed reactivity against CYP3A4 and CYP2E1 in about 20 to 30% and 10 to 20% of the alcoholic sera, respectively. No difference were noted between sera from alcoholics with or without hepatitis C virus infection, and only very little reactivity was seen in sera from control subjects. Western blotting analysis revealed anti-human CYP2E1 reactivity in 8 of 85 alcoholic sera and 3 of 58 control sera, whereas anti-CYP3A4 reactivity was detected in 18 of 85 alcoholic sera and 4 of 58 control sera, which were different from the sera reactive with CYP2E1. Immunoblot reactivity of CYP3A4-positive alcoholic sera was found against glutathione-S-transferase fusion proteins containing truncated forms of CYP3A4, and such sera were also able to immunoprecipitate in vitro translated CYP3A4. Seven of eight sera showed reactivity toward domains C-terminal of position Ser281, and 1 of 8 sera recognized autoepitopes within the region Thr207-Ser281. These findings indicate that alcoholics develop autoantibodies against CYP2E1 and CYP3A4 that the CYP3A4 C-terminal domain is a target for the autoantibody reactions among a subset of alcoholics. The novel finding of CYP3A4 autoantibodies and their significant expression among alcoholics warrants further investigation. Attention should be given to immune toxicity associated with CYP3A4 autoantibodies and cases of alcohol abuse that are accompanied by exposure to drugs and substances that are CYP3A substrates.

Variable increases of IgG and IgM antibodies in milk of IgA deficient women.

Serum, milk and saliva from seven IgA deficient mothers were studied for the presence of IgA, IgG and IgM antibodies to Escherichia coli and poliovirus antigens. Different variable patterns were obtained. One mother had very much increased IgM and IgG antibodies in milk and saliva against both antigens; the milk IgG antibodies were 11-14 times higher than the reference milk pool. Another mother showed also striking increases of both IgM and IgG antibodies in milk, as well as in saliva where the increases were much higher for the poliovirus than the E. coli antibodies. Yet another mother showed a certain increase of IgM but not of IgG antibodies in the milk. The uneven appearance of IgG and IgM antibodies in serum and secretions suggests local production. So do the differences of antibody avidities, the variations in IgG subclass distribution of antibodies and different patterns after isoelectric focusing (IEF)/immunoblotting analysis of antibody spectrotypes in secretions and serum. The study illustrates the variable patterns of compensatory increases of IgG and IgM antibodies which may occur in IgA deficiency. It also shows that the milk from IgA deficient mothers can still be rich in antibodies, in spite of the lack of secretory IgA.

Immunoblot characterization of IgG, IgM and IgE antibodies elicited during the course of fatal and non-fatal infections of Plasmodium berghei in DBA/2 and Balb/c mice.

When infected with the CRS line of Plasmodium berghei ANKA, DBA/2 mice died of a fulminating infection around day 20 post-infection whereas Balb/c mice had crises around day 15 then low or subpatent parasitaemias until approximately day 73, when sterile immunity is believed to have supervened. Immunoblots for parasite-specific immunoglobulins G, M and E were made from the sera taken during the course of infection in each mouse strain. Although both strains elicited antibodies to a 128-kDa antigen by day 8, this was solely of the IgG class in the DBA/2 but of both IgG and IgM in the Balb/c. Crisis and subpatency were associated with the appearance of IgG and IgM antibodies to 74- and 80-kDa antigens. The most vigorous immune response was observed in sera from the Balb/c mice on day 73, with antibodies to many antigens of 19-180 kDa; IgE antibody (to antigens of 38 and 45 kDa) was then evident for the first time.

Hepatitis E Virus: Another Addition to the Existing Alphabet of Human Hepatitis Viruses

Hepatitis E Virus: Another Addition to the Existing Alphabet of Human Hepatitis Viruses

The Origin of IgG Production and Homogeneous IgG Components After Allogeneic Bone Marrow Transplantation

Pediatric recipients (n = 25) of an allogeneic bone marrow (BM) graft were selected on the basis of informative IgG allotype (Gm) differences between the BM donor and the recipient. To investigate the kinetics of the appearance of IgG of donor origin and the disappearance of IgG of recipient origin, G1m and G2m allotype levels were quantified in sera obtained at regular intervals between 3 months and 5 years after BM transplantation (BMT). For this quantification, a dot immunobinding assay (DIBA) has been developed. In 19 of 22 informative recipients, the Gm allotype distribution had reached the range of values expected on the basis of the Gm phenotype of the donor within 6 months after BMT. Remarkably, IgG of recipient origin persisted in 15 of 18 informative recipients until last follow up, ie, for several years after BMT. In addition to the origin of total IgG production, the origin of homogeneous IgG components (H-IgG) appearing after BMT was investigated. H-IgG of donor origin could be detected as early as 3 weeks after BMT, but also H-IgG of recipient origin were present in 8 of 13 informative recipients for a period of up to 1 year after BMT. We conclude that host-type IgG-producing cells were not eradicated by the (myeloablative) conditioning regimen and persisted in a high number of graft recipients. It is our hypothesis that lack of graft-versus-host disease (GVHD) in the majority of these recipients results in the persistence of IgG-producing cells of host origin. These observations may be relevant for the evaluation of patients who received allogeneic BMT for the treatment of multiple myeloma.

An immunohistological study on the nephritis in chicks experimentally produced with avian nephritis virus

One chick inoculated by a combined nasal and conjunctival sac route (in) and two chicks inoculated per os (io) died with visceral urate deposits at post inoculation days (dpi) 9 and 11. All infected chicks showed renal degeneration and inflammatory changes that originated from tubular cell necrosis. Avian nephritis virus (ANV) antigen was detected as cytoplasmic granules within the necrotic tubular epithelial cells. The serum uric acid was increased in in- and io-infected chicks 5 to 10 dpi and was coincident with the severity of the renal degeneration. Immunoglobulin (IgG and IgM)-containing cells were detected first in the renal lesion 5 and 7 dpi; they were coincident with the cell infiltration. IgG- and IgM-containing cells were demonstrated in the spleen 5 dpi and increased thereafter eight to 12 times more than those in non-infected control chicks. They were almost coincident with the detection of antibody against ANV. These findings suggested that ANV replication may stimulate the proliferative response of IgG- and IgM-containing cells in the spleen, and that the appearance of IgG- and IgM-containing cells in the kidney may also be closely associated with the clearance of ANV and regeneration of the renal lesion.