Benign monoclonal gammapathy (BMG).
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Animals↗
Biomedical subjects
J Radl
Publications and source records attributed to J Radl.
Characteristics of IgA deposits in liver and skin of patients with liver disease.
The presence of IgA deposits in a continuous pattern along hepatic sinusoids is a specific entity for alcoholic liver disease. In superficial skin blood vessels of patients with liver disease, IgA deposits can occur. The authors characterized the deposits for IgA-subclass epitope expression and for macromolecular configuration (assessment of [hidden] J-chain determinants and of secretory component-binding capacity). A variety of monoclonal anti-IgA-subclass reagents were applied, which proved to be specific in control experiments on blastoid cells generated by pokeweed mitogen stimulation of blood mononuclear cells and frozen tissue sections of normal jejunum. IgA1 is the major component in IgA deposits in liver (n = 83) and skin (n = 31) of patients with liver disease. Macromolecular IgA is detectable in only one-fifth of the cases. The authors' data do not indicate that hepatic IgA deposits in liver disease are of gastrointestinal origin. Out of the circulating IgA pool, IgA1 appears to be most capable of being deposited in tissue.
Histocytochemistry↗
Influence of treatment with APD-bisphosphonate on the bone lesions in the mouse 5T2 multiple myeloma.
The effects of the treatment of multiple myeloma (MM) with APD-bisphosphonate on bone destruction, the dissemination pattern of the MM, and toxicity for normal and malignant cells were investigated in an animal model, the 5T2 MM. This mouse MM very closely resembles the human disease, including the typical bone lesions. It was demonstrated by radiography, microradiography, and histologic investigation that the treatment of the 5T2 MM with APD-bisphosphonate protected the mice against a loss of bone to a significant extent. It seemed that the treatment with APD not only diminished the bone destruction by the MM but also led to the formation of new bone in already-affected bone tissue. The growth pattern of the MM was not substantially influenced by the treatment, even though there was an indication that APD exerts some cytotoxic effect on the MM cells.
Animals↗
Quantitation of murine IgE in an automatic ELISA system.
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Aging↗
Monoclonal gammapathies in patients undergoing immunosuppressive treatment after renal transplantation.
The frequency of monoclonal gammapathies (MG) and their possible origin were investigated in renal graft recipients undergoing immunosuppressive treatment. In a cross-sectional study, homogeneous immunoglobulins were found in 30% of the patients investigated. This incidence was 10-times higher than that in a control group of patients with chronic renal failure on dialysis treatment. The increase in the frequency of homogeneous immunoglobulins in the renal transplant recipients was related to the age of the patients but not to the duration of the immunosuppressive treatment. A longitudinal study in 55 patients demonstrated that most of the MG reflected transient B-cell monoclonal proliferations, probably due to an immunodeficiency; however, the incidence of benign and malignant B-cell neoplasias seemed also to be unusually high. These findings indicate that the immunosuppressive treatment enhances and accelerates an immunodeficiency which develops spontaneously with aging of the immune system; it also may contribute to the development of other age-related, both benign and malignant monoclonal B-cell proliferative disorders.
Adult↗
Molecular forms of tear IgA and distribution of IgA subclasses in human lacrimal glands.
Tears and sera from 14 subjects were analyzed for IgA levels by radioimmunoassay by use of secretory IgA standards for tear samples and monomeric IgA standards for serum samples. [corrected] Tears from subjects without conjunctival inflammation contained 93% polymeric IgA (pIgA) and 7% monomeric IgA; tears from subjects with conjunctival inflammation had less pIgA (79%). Biopsy specimens of 11 lacrimal glands and one accessory lacrimal gland were obtained from 12 additional subjects. Tissues were stained with polyclonal antisera for immunoglobulins, J chain, and secretory component. In addition, tissues were stained for IgA subclasses with monoclonal reagents specific for IgA1 and IgA2. IgA plasma cells predominated over other types of plasma cells, and most were J chain positive. Secretory component, although absent from the interstitium of the gland, was found in most acinar and ductal cells. The average proportion of IgA1 to IgA2 cells was 56% to 44%. We concluded that the lacrimal system of the human resembles other exocrine systems in the production of predominantly pIgA and the nearly equal occurrence of IgA1 and IgA2 plasma cells.
Adolescent↗
Subclass distribution and molecular form of immunoglobulin A hemagglutinin antibodies in sera and nasal secretions after experimental secondary infection with influenza A virus in humans.
Serum and nasal wash specimens from 13 human volunteers undergoing experimental secondary infection with influenza A/Peking/2/79 (H3N2) wild-type virus were examined for the molecular form and subclass distribution of immunoglobulin A (IgA) antibodies to the viral hemagglutinin (HA). Nasal IgA antibodies were polymeric and did not bind radiolabeled secretory component, indicating that they were secretory IgA antibodies. Both IgA1 and IgA2 antibodies were detected; however, IgA1 accounted for most of the rise in IgA anti-HA levels seen after infection. In serum virtually all of the IgA HA antibodies were of the IgA1 subclass. Furthermore, the serum antibodies were predominantly polymeric and were capable of binding radiolabeled secretory component. These results suggested that the serum IgA antibodies to HA were of mucosal origin and that influenza A virus HA preferentially stimulates an IgA1 response.
Hemagglutinins↗
Occurrence of IgA subclasses (IgA1 and IgA2) in the human nervous system. Correlation with disease.
The occurrence of IgA subclasses in pathological conditions of the nervous system was studied by means of monoclonal antibodies and an indirect immunofluorescence technique. IgA1- and/or IgA2-positive lymphoid (plasma) cells were found in demyelinating diseases comprising multiple sclerosis, Guillain-Barré syndrome, and adrenoleukodystrophy, in various inflammatory diseases, and in tumors, some of which exhibited labeling of tumor cells. Demyelinating and inflammatory diseases with chronic course displayed some prevalence of IgA2-, and tumors some prevalence of IgA1-positive cells. This is the first demonstration of IgA1 and IgA2 in the nervous system.
Alzheimer Disease↗
Anti-major histocompatibility complex immunity detected prior to intentional alloimmunization. I. Naturally occurring H-2-specific antibodies in C57BL/KaLwRij (H-2b) mice.
Naturally occurring, H-2-specific, lymphocytotoxic antibodies were detected in 3-10% of young adult and in 10-40% of aged C57BL/KaLwRij (H-2b) mice. The antibodies were of the IgM class and occurred in low titers, but occasionally a high titer was found. The antibodies detected public lymphocyte-membrane antigens controlled by genes identical with, or closely linked to class-I H-2K and H-2D genes. Antibodies against 7 different allogeneic H-2 haplotypes were detected but sera of individual mice exerted different reaction patterns and some specificities occurred more frequently than others. Although the occurrence of the antibodies was age dependent, thymus involution, gammapathies, autoimmunity, the presence of other natural lymphocyte-specific antibodies, and polyclonal or nonspecific stimulation could not be related to the occurrence of natural H-2-specific antibodies. Several possible explanations of natural H-2-specific antibodies exist. We propose that determinants of complex altered self-MHC (MHC + X) antigen(s) triggered the production of H-2-restricted antibodies that recognize H-2-public determinants on normal allogeneic cells.
Age Factors↗
Light chain types of IgD in human bone marrow and serum.
One of the unexplained features of human IgD is its preferential expression with either kappa or lambda light chains in different situations. While the membrane IgD on B lymphocytes shows a predominance of the kappa type, about 90% of all known IgD myeloma proteins and 87% of normal IgD producing plasma cells in spleens of healthy individuals were shown to belong to the lambda type. Very little is known of the kappa/lambda light chain distribution of normal polyclonal IgD in the serum and in the bone marrow plasma cells. In this study, the kappa/lambda representation of IgD in bone marrow plasma cells and in the serum of 25 adult persons (two healthy and 23 suffering from various nonmalignant diseases) was investigated. The kappa/lambda ratio of IgD+ bone marrow plasma cells showed a large variation among the individuals of this group, in 84% of the cases being below 1.0. While about 1/3 of the investigated subjects had 80% or more of IgD of the lambda type (kappa/lambda ratio below 0.2), most showed a kappa/lambda ratio of IgD higher than that, with four persons exhibiting a clear cut predominance of IgD of the kappa type. A positive correlation (Spearman's correlation co-efficient, P = 0.005) between the percentages of IgD+ plasma cells and their kappa/lambda ratio was found. Semiquantitative evaluation of the kappa/lambda composition within the serum IgD by immunoselection was in agreement with the kappa/lambda ratio of IgD+ plasma cells in all individual cases.
Adult↗
Idiopathic paraproteinaemia V. Expression of Igh1 and Igh5 allotypes within the homogeneous immunoglobulins of ageing (C57BL/LiARij X CBA/BrARij)F1 mouse.
The role of genetic factors linked to the immunoglobulin loci and the development of idiopathic paraproteinaemia (IP)--a benign B-cell proliferative disorder--was investigated in F1 hybrid mice of low (CBA/BrARij) and high (C57BL/LiARij) IP frequency strains. Igh1 and Igh5 allotypes were used as markers for the (parental type) origin of homogeneous immunoglobulins (H-Ig) which appeared in the sera of the F1 mice with ageing. The frequencies of H-Ig in the F1 mice were intermediate with those of the parental strains. The isotype distribution of the H-Ig was 27%, 24%, 12%, 12%, 11%, 10%, 3% and 1% for IgG2a, IgM, IgG1, IgG3, IgG2b, IgD, IgA and IgE, respectively. H-Ig of the IgG2 subclass carried the Igh1b (C57BL) allotype in 98% and the Igh1a (CBA) allotype in 2% cases. Of the IgD H-Ig, 70% carried the Igh5b and 30% the Igh5a determinant. The Igh1 allotype distribution in the bone marrow and spleen plasma cells showed a large variation in the Igh1a/Igh1b ratio among old individual mice and often also between bone marrow and spleen within a single animal with or without a H-Ig component. The categorization of the paraproteinaemias on the basis of their origin showed that 10% of the H-Ig were the result of a transient monoclonal B-cell proliferation; multiple myeloma or lymphoma was found to be responsible for about 1% of the paraproteinaemias; H-Ig fulfilling the criteria for IP were detected in about 42% of cases. The origin of the remaining old age paraproteinaemias could not be determined. These data indicate that the F1 mice develop monoclonal proliferative disorders in a manner more similar to the C57BL than to the CBA parental strain. The allotype associated genetic material from the parental C57BL strain was shown to be mainly responsible for the development of IP in ageing F1 mice.
Aging↗
Monoclonal gammapathies. An attempt at a new classification.
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Animals↗
Anti-major histocompatibility complex immunity detected prior to intentional alloimmunization. II. Monoclonal H-2-specific antibodies obtained from an unimmunized C57BL/KaLwRij (H-2b) mouse.
A monoclonal 'natural' anti-H-2 IgM antibody produced by a hybridoma cell line OL-3.17 (H-2 m. 209) is described. The OL-3.17 monoclonal antibody was obtained by hybridization of spleen B cells from an unimmunized C57BL/Ka (H-2b) mouse in the serum of which simultaneously an IgM kappa paraprotein of high concentration and a natural H-2-specific antibody of high titer was detected. The monoclonal antibody OL-3.17 reacted strongly with H-2d and H-2s and weakly with H-2k,q,r lymphocytes, thereby detecting a hitherto unknown H-2 public determinant. The target molecules for OL-3.17 cocapped with class-I H-2 antigens, but immunoprecipitation of H-2 antigens was not achieved. This is the first monoclonal H-2-specific antibody obtained from a mouse without intentional immunization and, with high probability, was derived from a B-cell clone which produced natural H-2-specific antibodies detectable in the serum of the original mouse.
Age Factors↗
Hyperimmunoglobulinaemia D and periodic fever: a new syndrome.
Six patients of Dutch ancestry with a long history of recurrent attacks of fever of unknown cause were found to have a high serum IgD level and a large number of plasma cells with cytoplasmic IgD in the bone marrow. Because the clinical picture in some ways resembled that of familial Mediterranean fever (FMF), sera of patients with FMF were also investigated; only one of eight such patients had a raised serum IgD.
Adolescent↗
Increased incidence of homogeneous immunoglobulins in irradiated, reconstituted mice after prolonged treatment with 2'-deoxyguanosine.
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Animals↗
Differences among the three major categories of paraproteinaemias in aging man and the mouse. A minireview.
The frequency of homogeneous immunoglobulins markedly increases with aging. These homogeneous Ig, paraproteins, reflect three different major categories of disorders within the immune system: B-cell malignancies; B-cell benign proliferative disorders; and Secondary immunodeficiency, a T-B immune system imbalance due to aging. A correct differential diagnosis among these conditions is crucial for the prognosis and potential treatment. Recent studies in animal models offer some clues which are helpful for our better understanding of the mechanism of the development of the paraproteinemias and for their differential diagnosis.
Aging↗
Autoantibodies in highly aged humans.
The presence of 14 different autoantibodies was determined in 65 persons, aged 95 years and older, without overt disease. The prevalence of positive anti-immunoglobulin latex tests, of autoantibodies against nuclear components and against thyroid microsomes was significantly increased. This selective increase of autoantibodies of low titre and without cluster formation is considered to be the result of a loss of control within the immune system due to ageing, rather than as a sign of latent disease.
Aged↗
Circulating and mesangial secretory component-binding IgA-1 in primary IgA nephropathy.
In a prospective study of 38 patients who presented with hematuria of renal origin, 15 patients were found to have primary IgA nephropathy and 23 had other renal disorders. Sera and renal biopsy specimens of these patients were studied for the presence of macromolecular IgA1 and IgA2 using monoclonal antibodies, and the presence of J-chain as demonstrated either by immunofluorescence or its capacity to bind free secretory component. Circulating macromolecular IgA was found exclusively in the sera of patients (80%) with primary IgA nephropathy. In these sera the polymer/monomer ratio for IgA1 (0.64 +/- 0.13) was significantly higher than for normal human serum (0.39 +/- 0.01) (P less than 0.001), while no differences were found for IgA2. The polymeric IgA1 was isolated from serum by gel chromatography and was shown to have the capacity to bind free secretory component. Direct two-color immunofluorescence studies revealed the presence of only IgA1 in the mesangial deposits and also its capacity to bind free secretory component. We conclude (1) that demonstration of circulating macromolecular IgA in patients with renal hematuria is of diagnostic value and (2) that antigenetic similarities between the circulating and the mesangial macromolecular IgA suggest that dimeric IgA1 is deposited in the mesangium of patients with primary IgA nephropathy.
Antibodies, Monoclonal↗