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Aims: The aim of the present study was to investigate the presence of immunoglobulins (Ig) in whole saliva from patients affected by autoimmune hepatitis (AIH)., Design: Twelve individuals with AIH and 12 healthy individuals without (CON) autoimmune hepatitis, aged 8-18 years, participated in this study. Non-stimulated whole saliva was collected and centrifuged. Supernatants were separated and lyophilized. Salivary pH was measured and immunoglobulins were analyzed through ELISA technique., Results: Salivary pH (CON, 7.17 ± 0.45; AIH, 6.92 ± 0.43) did not differ between groups (p = 0.183). Measurable levels of IgG, IgA, IgM and IgE were detected on all patients. IgG levels were higher in AIH individuals (CON, 1.058 ± 0.386; AIH, 1.635 ± 0.373; p = 0.001), whereas IgA (CON, 0.915 ± 0.187; AIH, 0.995 ± 0.235; p = 0.362), IgM (CON, 0.683 ± 0.147, AIH, 0.646 ± 0.161; p = 0.561) and IgE levels (CON, 1.241 ± 0.378; AIH, 1.312 ± 0.412; p = 0.664) did not present differences between groups., Conclusions: The results of the present study suggest differences in salivary IgG levels between individuals with and without AIH. Thus, saliva has the potential of becoming an important diagnostic tool for the assessment of AIH., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We studied the prevalence and nature of immunoglobulin abnormalities in HIV-1-infected patients in the era of highly active antiretroviral therapy. Protein electrophoreses (PEP) were performed on and quantitative immunoglobulin levels obtained in samples from 320 consecutive HIV-1-infected patients. Samples with possible PEP abnormalities underwent immunofixation. The PEP pattern was normal in 83.8% of samples, 8.1% had subtle oligoclonal banding, and 4.4% had a low-concentration (<5% of total protein) monoclonal band. Hypogammaglobulinemia and polyclonal hypergammaglobulinemia accounted for 1.9% each. In multivariate analysis, younger age (odds ratio [OR], 1.06 with each decreasing year of life; 95% confidence interval [CI], 1.02-1.11; P = .016), female sex (OR, 2.4; 95% CI, 1.13-5.11; P = .02), viral load (OR, 1.50 with each increasing logarithmic viral load of 1.0; 95% CI, 1.14-1.98; P = .004), and CD4 cell count (> or =350 vs <350/microL [0.35 x 10(9)/L]) (OR, 2.71; 95% CI, 1.09-6.75; P = .032) were associated with monoclonal or oligoclonal banding. These results suggest that younger HIV-1-infected patients with a more robust immune system (higher CD4 cell count), which is stimulated by uncontrolled viremia, are most likely to have an augmented B-cell response to HIV infection. One manifestation of this B-cell response is low-concentration monoclonal banding in 4.4% of the patients studied.

We report the clinical findings and analysis of the immunoglobulin (Ig) composition of the vitreous of a 10-year-old girl with juvenile rheumatoid arthritis-associated uveitis. The vitreous had a schlieren appearance at the time of pars plana lensectomy and vitrectomy. Analysis of the vitreous fluid revealed marked elevation of IgG, IgM, IgA, and albumin levels relative to vitreous fluids from control patients without uveitis. The immunoglobulin coefficients were also elevated for the IgG and IgM classes of immunoglobulins. Immunofixation electrophoresis of the vitreous fluid revealed 2 distinct bands of restricted electrophoretic mobility. These studies suggest that there may be local (intraocular) production of immunoglobulins as an immunologic response in ocular inflammatory diseases such as juvenile rheumatoid arthritis-associated uveitis and that this immunologic response may be monoclonal (possibly biclonal or oligoclonal) in nature.

Scavenger receptor (SR)-specific delivery by maleylation of a ubiquitous self-protein, Ig, to SR-bearing APCs results in self-limiting induction of autoimmune effects in vivo. Immunization with maleyl-Ig breaks T cell tolerance to self-Ig and causes hypergammaglobulinemia, with increases in spleen weight and cellularity. The majority of splenic B cells show an activated phenotype upon maleyl-Ig immunization, leading to large-scale conversion to a CD138+ phenotype and to significant increases in CD138-expressing splenic plasma cells. The polyclonal B cell activation, hypergammaglobulinemia, and autoreactive Ig-specific T cell responses decline over a 2-mo period postimmunization. Following adoptive transfer, T cells from maleyl-Ig-immune mice taken at 2 wk postimmunization can induce hypergammaglobulinemia in the recipients, but those taken at 10 wk postimmunization cannot. Hypergammaglobulinemia in the adoptive transfer recipients is also transient and is followed by an inability to respond to fresh maleyl-Ig immunization, suggesting that the autoreactive Ig-specific T cells are inactivated peripherally following disruption of tolerance. Thus, although autoreactive T cell responses to a ubiquitous self-Ag, Ig, are induced by SR-mediated delivery to professional APCs in vivo resulting in autoimmune pathophysiological effects, they are effectively and rapidly turned off by inactivation of these activated Ig-specific T cells in vivo.

The goal of this study was to determine whether class I proteins play an important role in the regulation of Ig and to elucidate the mechanism(s) involved. We analyzed the phenotype imposed by a null allele of beta 2-microglobulin (beta 2m). Serum Ig levels of several mouse strains showed a beta 2m dependence that was most evident in mice genetically predisposed to develop chronic systemic lupus erythematosus, was preferential to IgG isotypes, and was greatly exaggerated in aging mice that normally develop hypergammaglobulinemia. Beta 2m-deficient mice, regardless of genetic background, also displayed a substantial reduction of specific Ab in response to a prototypic T cell-dependent Ag and a prototypic T cell-independent 2 Ag. This reduction could be accounted for by a selective diminution of Abs of the IgG class. Therefore, class I proteins play a considerable role in the regulation of Ig. The beta 2m dependence could not be explained by class I-dependent immunoregulatory cells (CD8+ cells, NK1.1+ T cells, or conventional NK+ cells) or by the transfer of maternal IgG into the prenatal/neonatal mouse made possible by the beta 2m-dependent Fc receptor (FcRn). However, a beta 2m-dependent increase in the half-lives of IgG, presumably conferred by lifelong FcRn expression, was observed in all mice regardless of genetic background and age. We conclude that FcRn-mediated protection of IgG from catabolism is a generic mechanism that best explains the lifelong beta 2m dependence of Ig in both normal and pathologic situations.

We studied the ability of B lymphocytes from patients with X-linked hyper IgM syndrome (HIGM1) to be activated via the CD40 membrane receptor. HIGM1 is caused by a CD40 ligand gene mutation, leading to defective expression on the membrane of activated T lymphocytes. We found that triggering of B cells by an anti-CD40 monoclonal antibody or the soluble CD40 ligand plus interleukin (IL)-4 or IL-10 led to B cell proliferation and/or differentiation towards IgG, IgA and IgE secretion. This was reflected by transcription of C gamma, alpha and epsilon membrane isotype expression and IgG, IgA and IgE production. These results confirm the integrity of B cells in patients with the HIGM1 immunodeficiency and open up new therapeutic possibilities.

In clinically quiescent SLE hypergammaglobulinaemia, presence of autoantibodies, and increased soluble IL-2 receptors (sIL-2R) have been reported, suggesting persistent B as well as T cell activation. In contrast, the primary immune response to test antigens is markedly decreased. To analyse these phenomena at a cellular level, we undertook a cross-sectional study on 13 non-active SLE patients and 15 controls. We determined the composition of lymphocyte subsets with special attention to activation markers (CD25, HLA-DR, CD38) and the presence of naive T cells (CD45RO-), and related those findings to serological parameters. In non-active SLE patients the expression of activation markers on B cells and T cells was higher than in normal controls (P < or = 0.02), but was not interrelated. Percentages of activated B cells in SLE were related to levels of total IgG (P < 0.02) and IgM (P < 0.02) but not to anti-dsDNA, suggesting a disordered immune system also in clinically quiescent SLE. Numbers of CD4+ cells (P < 0.001) and CD4+CD45RO- cells (P < 0.05) were decreased. The latter finding might explain the anergy to primary test antigens in clinically quiescent SLE.

Several human monoclonal immunoglobulins with the same autoantibody activity have been shown to have cross-reactive idiotypes (CRI). In this study, using polyclonal anti-idiotypic antibodies, we found that 28% of human monoclonal immunoglobulins with polyreactive autoantibody activity from myeloma, Waldenström's macroglobulinaemia and cryoglobulinaemia patients shared common idiotype(s). Furthermore, the latter were expressed on human and murine natural MoAbs (respectively in 12% and 22% of the clones tested) and on human IgG preparations used for therapeutic intravenous injections (IVIg) and which contain natural antibodies. These findings suggest that monoclonal immunoglobulins could arise from the proliferation of a clone that normally produces a natural antibody. The existence of common idiotype(s) between monoclonal immunoglobulins and IVIg could be relevant to the improvement noted after treatment with IVIg in patients suffering from peripheral neuropathies associated with monoclonal gammopathy.

Two different types of monoclonal human immunoglobulins (M-components) with antistreptolysin-O (ASO) activity were investigated. The M-component FM with essential monoclonal gammopathy revealed to have an ASO activity, demonstrated not only by streptolysin-O neutralizing assay according to Ranz-Randall's method, but also by passive agglutination assays and precipitation on agar. The ASO activity was shown to reside in the Feb. These findings suggest that the M-component FM have a true antibody activity. On the other hand, ASO activity of M-component TT with multiple myeloma was detected only by streptolysin-O neutralizing assay, but the passive agglutinating assays and precipitation on agar showed no positive results. It has not been fully confirmed if the M-component TT behaves as a true antibody activity. Heterogeneity of the M-components with ASO activity was discussed.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

We studied cell surface membrane immunoglobulins (SmIg), intracytoplasmic Ig (CIg) and monoclonal Ig (M protein) in patients with the B-cell series malignancies; malignant lymphoma, chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia (WM), multiple myeloma (MM), and monoclonal gammopathy (MG) associated with Sjögren's syndrome (SS). The patients were examined for idyotype (Id) determinants on the cell surface and in the cytoplasm of malignant cells as well as serum M proteins. Twenty-two patients had malignant lymphoma with monoclonal SmIg. The malignant cells of 11 patients contained CIg; four of these 11 patients had a small amount of serum M protein. SmIg of the IgM class was most frequent (12/22) and the lambda type light chain was predominant (kappa/lambda ratio = 4/8). By means of rabbit anti-Id antisera prepared against M proteins, Id determinants were demonstrated on the cell surface and in the cytoplasm of malignant cells as well as in the serum M proteins, indicating that the malignant cells proliferated monoclonally producing monoclonal IgM on the cell surface and in the cytoplasm and secreting it to the serum. Six CLL patients were included in our series; one manifested monoclonal IgM in the serum. The Id determinants of M protein was detected on the cell surface and in the cytoplasm of pathologic cells in the peripheral blood. Eight of ten WM patients were examined for SmIg; all had monoclonal SmIg on the surface of cells from peripheral blood or bone marrow. Id determinants were detected on the cell surface and in the cytoplasm of malignant cells in four WM patients. There were 42 patients with MM; 10 of them were examined for SmIg and three of these had monoclonal SmIg on plasma cells derived from the bone marrow. By immunofluorescent and mixed rosette methods, Id-bearing B (0-20%) and T cells (0-2%) were identified in the peripheral blood of MM patients who had no plasma cells in the peripheral blood. Our findings suggest that a monoclonal change may occur at the B-cell level and that Id-bearing T cells may exist as regulatory T cells. Ten SS patients had M proteins. Non-IgM class M proteins (2 IgG and 4 IgA) were more frequent than the IgM class (3 IgM). Four M proteins with rheumatoid factor (RF) activity were found among these 10 M proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunoglobulin-secreting cells were enumerated in the peripheral blood of 31 patients with multiple myeloma, nine patients with so-called benign monoclonal gammopathy, and ten patients with polyclonal hypergammaglobulinaemia or idiopathic hypogammaglobulinaemia. Immunoglobulin-secreting cells were detected by a haemolytic plaque assay using protein-A-coated erythrocytes in the presence of class- or type-specific rabbit anti-human immunoglobulin antisera. In about two-thirds of patients with multiple myeloma, cells secreting the same light-chain isotype of their serum M-protein increased in number, whereas this was not the case in the patients with so-called benign monoclonal gammopathy. Follow-up studies of immunoglobulin-secreting cells in multiple myeloma revealed that these cells increased or decreased, correlating with the severity of the disease, and alterations were more rapid than other clinical features. This plaque assay is therefore useful in evaluating the response to chemotherapy in patients with multiple myeloma.

Cell suspensions of bone marrow and lymphoid tissue from 85 patients with monoclonal gammapathy were investigated by a direct immunofluorescence procedure for the detection of intracellular immunoglobulin alpha, mu, gamma, kappa and lambda chains. Serum Ig levels were determined and daily syntheric rates estimated. In all cases the majority of Ig-containing bone marrow cells contained the same Ig class as that of the M-component in serum or urine indicating a diffuse distriubtion of these clones in the bone marrow. This was observed not only in myeloma but also in benign monoclonal gammapathy (BMG) and lymphoma with an M-component. The M-component producing clone could be traced to extramedullary lymphoid tissue in myeloma but usually not in BMG. A positive correlation was found between the calculated synthetic rate of the M-component and the number of Ig-containing cells in the bone marrow and some indication was found that the synthetic rate per cell might be lower in IgM and IgG than in IgA monoclonal gammapathy. The depressed level of polyclonal Ig in myeloma and to some extent in BMG was parallelled by a diminished number of Ig-containing cells in the bone marrow.

A complex between serum albumin and immunoglobulins was observed on immunoelectrophoresis in six patients. Two patients with multiple myeloma had monoclonal IgA-albumin complexes; one of these complexes was formed by covalent bonds and the other by non-covalent bonds. Four patients displayed non-covalent IgG-albumin complexes: of these, one had multiple myeloma, two had been treated with nitrofurantoin for prolonged periods, and one had diabetes mellitus. The IgG-albumin complex of the last patient was subjected to a detailed immunochemical analysis. The albumin-specific antibodies were isolated by affinity chromatography and analysed, using a sensitive tritium labelling technique. The antibodies were polyclonal, complexed with serum albumin through their Fab portion, and showed a high specificity for the human albumin as compared with bovine and rabbit albumins. The serum albumin of two patients displayed an abnormal behaviour in reduced SDS-polyacrylamide gel electrophoresis (PAGE). The abnormal albumins had an apparent molecular weight of 52,000 and could react with rabbit anti-human serum albumin like the normal protein. No abnormal albumin could be detected in 20 other patients' sera, including nitrofurantoin-treated patients and normal controls. These findings suggest a possible role for an altered self-component in the triggering of a specific autoimmune reaction.

Peripheral blood samples collected from normal individuals and patients with benign monoclonal gammopathy (BMG) were separated and assayed for their T-cell subpopulations, PHA blast formation as well as immunoglobulin (Ig) synthesis in vitro. Bone marrow cells of most the cases were also assayed for Ig synthesis. Age-related changes of T-cell subsets and PHA blast formation revealed a marked leveling off after the 8th decade. Comparing the age-related increase in Ig synthesis in peripheral blood lymphocytes, PWM-induced Ig synthesis of bone marrow cells was only slightly increased. The distribution of values for T-cell subsets, PHA blast formation and Ig synthesis in the BMG cases more closely resembled that in the aged than that in the age-matched controls. Immunoregulatory functions seem to be affected in BMG.

Peripheral blood mononuclear cells (PBM) from four patients with IgG myeloma and four patients with benign monoclonal gammopathy (BMG) were stimulated with pokeweed mitogen (PWM), and the in vitro immunoglobulin production over 7 days was measured with an enzyme-linked immunosorbent assay. All myeloma patients were sufficiently treated with cytostatic drugs. Their PBM did not produce monoclonal Ig in vitro, as opposed to PBM from two patients with BMG. Unseparated PBM from myeloma patients produced smaller amounts of polyclonal Ig than unseparated cells from normal donors. However, macrophage-depleted PBM from myeloma patients produced amounts of Ig comparable to those of normal donors when autologous or allogeneic adherent cells were returned in defined numbers. T cells from three of the four myeloma patients could provide help for the Ig production by B cells from healthy donors. These results indicate that functionally normal polyclonal B cells circulate in the blood of myeloma patients. The circulating T-cell population also has no obvious defect. In contrast, blood macrophages seemed to be altered with respect to their regulating function for polyclonal Ig production. The results obtained by using cell populations from patients with BMG did not differ from those of healthy people.

Precise immunologic analysis of monoclonal immunoglobulin components is essential to allow proper diagnosis, monitoring of therapy and a clearcut understanding of the biosynthetic derangements in plasma cell neoplasms. Such analyses have resulted in the delineation of a number of well-defined clinical syndromes, such as the group of heavy chain diseases.

In a group of patients with chronic liver diseases (CLD), including both chronic active hepatitis of 'immunological' type and alcoholic cirrhosis, simultaneous measurements were made of serum immunoglobulin levels, in vitro synthesis of immunoglobulin by peripheral blood mononuclear cells, and in vitro short lived suppressor cell activity. In both forms of CLD, decreased short lived suppressor cell activity was found. There was a strong linear correlation between the amount of IgG released into supernatant of 7 day in vitro cultures and the serum IgG levels amongst patients with CLD. There was also a strong inverse correlation in the patient group between in vitro synthesis of IgG and IgA and the suppressor cell activity measured in the same cell population, suggesting that the short lived suppressor cell test may reflect activity of cells modulating immunoglobulin both in vitro and in vivo.

By applying sera containing various myeloma proteins to thin-layer isoelectric focusing at various pH ranges, we found that the best range of pH gradient for the detection of the band group specific for monoclonal immunoglobulin was from 5 to 8. The lowest concentration of monoclonal immunoglobulin detected by this method was approximately 0.1 mg/ml which was 8 to 32 times lower than the concentration detectable by cellulose acetate membrane electrophoresis or immunoelectrophoresis in routine laboratory use. Monoclonal protein concentration from 0.1 to 20 mg/ml was determined quantitatively. Blind tests on sera resulted in a disagreement between the concentration of monoclonal immunoglobulin assumed from the results of cellulose acetate membrane electrophoresis and immunoelectrophoresis and that determined by isoelectric focusing. These results suggest that isoelectric focusing is useful for the surveillance of monoclonal immunoglobulinemia provided that the technique and equipment are improved for laboratory tests.

The relationship between serum and CSF IgG has been analysed: (1) In patients with a normal CSF concentration of albumin, no correlation can be demonstrated between serum IgG and CSF IgG. (2) In cases where the CSF albumin concentration is elevated (i.e. transudation), local synthesis of IgG can be determined by reference of the degree of transudation of albumin and the serum IgG concentration. The combination of local IgG synthesis and transudation (meningitic pattern) is common. Most pure transudates are of "non-inflammatory" type. A very simple formula is proposed which evaluates the relationship between local and general immunity in all neurological diseases.

In a group of patients with monoclonal gammopathies a decrease in the serum anion gap was seen with increasing serum concentrations of monoclonal IgG and IgM but not monoclonal IgA. This was probably related to the fact that IgG and IgM are cationic but IgA is a anionic at a physiologic pH. The serum sodium level decreased by 0.7 mmol/l for every increase of 1 g/dl in the serum level of the monoclonal immunoglobulin, likely because of the volume displacement effect of the monoclonal protein.

The relative cytoplasmic immunoglobulin content of fixed plasma cells taken from the bone marrow of five patients with myeloma and five patients with benign monoclonal gammopathy was determined with a microscope fluorometer. In eight of the ten piasma cell populations studied, the distribution of the fluorescence intensities was close to normal. In three of these eight populations a significant difference in the variances of the heavy and light chain fluorescence intensities was found. Variances of heavy and light chain fluorescence intensities were smaller in patients with an immunoglobulin A-type gammopathy than in those with an immunoglobulin G-type gammopathy. No difference was found if normalized relative frequency distribution patterns of heavy or light chain fluorescence intensities of patients with myeloma were compared with those of patients with benign monoclonal gammopathies.

Lymphocytes and plasma cells in the peripheral blood and bone marrow of patients with multiple myeloma, benign monoclonal gammopathy and Waldenström's macroglobulinaemia were investigated for their cytoplasmic immunoglobulin distribution. Anti-idiotypic sera were used as markers for monoclonality. Double-wavelength fluorescence microscopy made it possible simultaneously to use anti-isotype and anti-idiotype sera with different fluorochromes. It was concluded that, in the bone marrow, the monoclonal event starts at the level of a lymphoid cell which has already been committed to its final isotype. The size of the monoclonal expansion in the bone marrow and the cell types involved in the proliferation may determine whether spread occurs. Polyclonal lymphoid cells containing cytoplasmic immunoglobulins were decreased in the peripheral blood and exhibited a reversed kappa/lambda ratio when compared to the immunoglobulin-containing cells in the bone marrow. This finding suggests a light chain-type related depression of polyclonal B cell precursors.

We describe a technique for estimating the mass of anti-DNA antibodies by immunonephelometry of serum immunoglobulins (IgG, IgA, IgM) before and after adsorption onto DNA bound to agarose-polylysine columns. Sixteen patients with systemic lupus erythematosus and 16 age- and sex-matched controls were studied. Precision was determined for high-value (in 10 patients) and low-value (in nine controls) ranges for each of the immunoglobulins. Within-run CVs ranged from 3.0% (IgG, controls) to 11.8% (IgA, patients); between-run CVs ranged from 15.5% (IgG, patients) to 25.2% (IgM, patients). We found anti-DNA antibody concentrations (mean +/- SD) in systemic lupus erythematosus of 1.981 +/- 1.015 g/L for IgG (controls: 0.243 +/- 0.231, p less than 0.001), 0.257 +/- 0.215 g/L for IgA (controls: 0.038 +/- 0.035, p less than 0.001), and 0.282 +/- 0.234 g/L for IgM (controls: 0.191 +/- 0.165, p greater than 0.05). Sensitivity and linearity are such that fivefold dilutions of patients' serum with either a buffered albumin solution or control serum yielded values close to the expected values for IgG. Similarly diluted sera gave inordinately high values in the radiometric binding assay. Neither parametric (linear regression) nor nonparametric correlation methods (Spearman's rank and Kendall's tau) show a significant correlation between patients' data obtained by the present technique and that by a radiometric binding assay (p greater than 0.05), although combined data from patients and controls demonstrate a significant nonparametric correlation (p less than 0.005 for Spearman's and p less than 0.02 for Kendall's).

The purpose of this study was to examine the relationship between immunoglobulin production and immunoglobulin levels in bronchoalveolar lavage (BAL) fluid and serum of normal subjects and patients with sarcoidosis. Eleven normal volunteers and 17 patients were studied. In normal subjects, no important relationship existed between the number of immunoglobulin-secreting cells and immunoglobulin levels in BAL or serum. By contrast, in patients with sarcoidosis, a highly significant correlation existed between the number of IgG secreting cells and IgG/alb% in BAL (p = 0.008) and between the number of IgG secreting cells in BAL and serum IgG mg/ml (p = 0.002). Similar associations did not exist for IgA and IgM. These data demonstrate for the first time the relationship between immunoglobulin production and immunoglobulin levels in normal persons, and convincingly show that immunoglobulin production at sites of disease activity is responsible for hypergammaglobulinemia in BAL and serum of patients with sarcoidosis.

Cytoplasmic immunoglobulins in human bone marrow plasma cells and lymphoid cells were characterized by direct immunofluorescence with fluorochrome-labelled reagents specific for immunoglobulin heavy and light chains. The percentage distribution of cells containing IgA, IgG or IgM and kappa- or lambda-immunoglobulins was determined in bone marrow samples from 168 immunologically normal individuals, in 11 patients with polyclonal increase of bone marrow plasma cells and in 80 patients with benign or malignant monoclonal gammopathies. A clear differentiation between monoclonal and polyclonal cell populations could be obtained in all cases.

Immunoglobulin quantitation was performed on pretherapy sera from 120 patients who had non-Hodgkin's lymphoma in an attempt to correlate abnormalities with histologic cell type and pattern. Patients with diffuse lymphomas had significantly (P less than 0.05) higher levels of IgG and IgA than patients with follicular lymphomas. Furthermore, polyclonal hyperimmunoglobulinemia was overall more common than hypoimmunoglobulinemia, and abnormally high immunoglobulin levels were most frequently found in patients who had diffuse histologic patterns. The highest values were associated with either lymphomas composed of T (thymus-derived) cells or large B (bursa-derived) cells. The incidence of quantitative immunoglobulin abnormalities in patients with T-cell lymphomas was comparable with that in patients with B-cell lymphomas. These abnormalities in the former group of patients were exclusively above the normal range, whereas they were equally above and below the normal range in the latter group. The frequent polyclonal hyperimmunoglobulinemia in patients with T-cell lymphomas may be related to the pathophysiology of these lesions.

A 52-year-old white male with a 26 year history of multiple sclerosis developed a monoclonal gammopathy of the IgA class, with reciprocal depression of normal immunoglobulins. A bone marrow aspirate and biopsy showed a marked increase in plasma cells, many of which appeared immature. These findings fulfilled the diagnostic criteria for multiple myeloma. The association of multiple myeloma with multiple sclerosis may not be coincidental. Mechanisms regarding this association are discussed.

Humoral (or antibody) immunodeficiency syndromes may occur as apparent congenital or acquired abnormalities, with deficiencies in all or in only some classes of immunoglobulins. Most patients are recognized because of recurrent infections with high-grade extracellular encapsulated bacterial pathogens, but some with selective IgA deficiency or with transient hypogammaglobulinemia of infancy may have few or no infections. Although general population statistics are not available, most defects are thought to be rare; humoral immunodeficiency is more prevalent than cellular immunodeficiency, possibly due to early death from the latter defects. Disorders affecting B-cell function may be inherited as X-linked recessive or as autosomal traits. Although considerable information exists about such defects at a functional and cellular level, the primary biologic errors are as yet unknown for all of them. Apparent abnormalities of B-cell maturation and/or intrinsic B-cell malfunction are seen in a majority of these defects. The heterogeneity of B-cell morphology and function in large pedigrees of patients with X-linked agammaglobulinemia makes it unlikely that the defect is due to a distinct gene rearrangement abnormality at a specific stage of B-cell maturation. Early recognition of B-cell deficiency and institution of adequate immunoglobulin replacement therapy can prevent extensive damage to the lungs and other life-threatening problems from infection and allow a relatively normal childhood and adult life.

We have measured immunoglobulin (Ig) synthesis by circulating lymphoid cells of 20 patients with cirrhotic hyperglobulinemia (CH) and 20 age-matched controls. We used specific anti-Ig antisera to precipitate Ig synthesized from [14C] amino acid precursors in 13 controls and employed an electroimmunoassay of the "rocket" type to measure Ig elaborated by cultured cells in 4 patient-control pairs. In addition, we studied 3 patient-control pairs by absorption of elaborated Ig onto an anti-Ig-coated solid phase, bromoacetylcellulose. The synthetic index (SI; the ratio of Ig synthesis by a CH patient and a control) was elevated in every case. Mean SI by coprecipitation was 7.2 +/- 5.4 (mean +/- SD), by rocket" 7.3 +/- 3.0 for IgG and 2.2 +/- 0.8 for IgA, and by immunoabsorption 13.8 +/- 8.4 for IgG. Three cirrhotic nonhyperglobulinemic patient-control pairs showed a mean SI of 1.0 +/- 0.1. CH and control populations showed equal numbers of membrane Ig-positive B lymphocytes by immunofluorescence. We conclude that (1) peripheral blood lymphoid cells are appropriate for study of differences in Ig synthetic capacity among individuals; (2) CH is associated with increased in vitro Ig synthesis; and (3) CH lymphocytes may be an appropriate cell population for the study of control mechanisms in Ig synthesis.

In 1000 patients with monoclonal gammapathies, heavy and light chains typing of the monoclonal Ig was performed. Class distribution of the heavy chains showed the following percentages : IgG = 56.60%; IgA = 17.0%; IgM = 14.5%; IgD = 0.3%; Light chain gammapathies (including Bence-Jones proteinuria without serum M-component) = 11.6%. The chi/lambda ratio was 663/337. Such results agree with figures from most statistical studies. Beside the well-known linkage between IgM and chi types in pathological macroglobulinemia, the quite high incidence of lambda chain type of light chain components is to be noticed. The frequency of gamma G type of M-component is significantly higher in patients demonstrating no symptoms of myeloma or lymphoma. chi/lambda ratio seems to be slightly affected by aetiological features.

Multiple myeloma and benign monoclonal gammopathies are regarded as monoclonal B cell proliferations in which B lymphocyte maturation is blocked in the final stages of the differentiation cycle. "Blocked" cells accumulate in the body and produce large quantities of immunoglobulins. These are monoclonal, because they come from a monoclonal cell stock. This study presents the results of peripheral B lymphocyte and marrow plasma cell typing designed to reveal the postulated isotypical relationship of the proliferating cells and the serum paraprotein. A good, though not absolute correlation between the two immunoglobulins was noted in most patients. The data, however, was not used in the diagnosis and treatment of these diseases. Further studies with MoAb's will, perhaps, provide a finer subclassification of the B lymphocyte proliferation diseases and assist in their diagnosis and treatment.