Suppression of polyclonal immunoglobulins in multiple myeloma: Relationship to the staging and other manifestations at diagnosis

Pruzanski, W.; Gidon, Martie; Roy, Ann W.

doi:10.1016/0090-1229(80)90097-5

Cited by 60 publications

(33 citation statements)

References 16 publications

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“…A deficiency both of normal polyclonal immunoglobulins and functional immunity is common in patients with multiple myeloma (1)(2)(3)(4)(5)(6). One potential mechanism is a deficiency of normal B cells.…”

Section: Introductionmentioning

confidence: 99%

“…Investigations of B cell number in peripheral blood have yielded confficting information. Increased, normal, and reduced polyclonal B cell numbers have all been described Receivedfor publication 6 December 1983 and in revisedform 24 May 1984. (7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…First Anti-idiotypic antibody was produced by immunization of mice with monoclonal protein that had been purified on protein A or DEAE-columns. The IgG fraction of serum was passed one to two times through Sepharose 4B (Pharmacia Fine Chemicals, Dorval, Quebec) coupled with eight different monoclonal proteins and HGG as described (6), to remove antibody directed against common determinants on Ig and assayed in enzyme-linked immunosorbent assay for specificity.…”

Section: Introductionmentioning

confidence: 99%

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Severe deficiency of B lymphocytes in peripheral blood from multiple myeloma patients.

Pilarski¹,

Mant²,

Ruether³

et al. 1984

J. Clin. Invest.

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Abstract. A major problem in the assessment of circulating B lymphocytes in multiple myeloma is the extent to which cells with passively absorbed Ig contribute to the assay. We have analyzed peripheral blood B cell numbers in 51 patients in various treatment categories by using an assay that is not subject to artifacts involving cytophilic Ig. We have defined a B lymphocyte by three different criteria (a) expression of a high surface density of Ig (b) expression of a high density of HLA.DR and (c) expression of a marker exclusive to surface Ig' B cells. By these criteria, normal individuals have an average of 6% B cells. In multiple myeloma patients, B cell levels in purified mononuclear cell preparations are severely reduced. Untreated patients and the majority of patients on intermittent chemotherapy have 20-600-fold fewer B cells than do normal donors (average = 0.3%). This decrease was even greater in whole blood of patients as compared with normal donors (100-1,000-fold fewer B cells). The number of B cells did not correlate with disease status or paraprotein concentration. We found no evidence to support the idea that B lymphocytes in patients include a substantial monoclonal subset.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Severe deficiency of B lymphocytes in peripheral blood from multiple myeloma patients.

Pilarski¹,

Mant²,

Ruether³

et al. 1984

J. Clin. Invest.

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“…In the study by Sari et al [5], suppression of uninvolved immunoglobulins was related to lower survival, although the findings were not statistically significant. Another similar study conducted by Pruzanski et al [9] showed that the degree of suppression of uninvolved immunoglobulins was related to worsened prognostic factors, but its effect on survival was not assessed. In contrast to the abovementioned papers, 2 studies [6,7] reported that the suppression of other isotypes (e g, IgA, or IgM for IgG-kappa myeloma) could not affect patients' outcome.…”

Section: Discussionmentioning

confidence: 93%

Role of Suppressed Immunoglobulins in Outcome of Patients With Multiple Myeloma

Jalaeikhoo

Rajaeinejad

Keyhani

et al. 2017

mcij

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Introduction: Multiple myeloma (MM) is typically presented with abundant monoclonal secretion of one type of immunoglobulin. The other classes of immunoglobulins, which are uninvolved and not secreted by malignant plasma cells, could be decreased. A number of previous studies reported the effect of suppression of uninvolved immunoglobulins on the outcome of patients with myeloma. However, its effect in regard to the type of treatment was not studied so far. The current study aimed at investigating the effect of uninvolved immunoglobulins suppression on the outcome of patients with myeloma in each individual type of treatment. Methods: In the current retrospective study, 140 myeloma cases diagnosed from 1999 to 2016 were studied. Patients were divided into 2 groups according to the first-line chemotherapy: 58 cases treated with Velcade-based and 81 cases with other agents. In the 2 groups, the effects of immunoglobulin suppression as well as other prognostic parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. Results: The effect of immunoglobulin suppression on patients' outcome depended on the type of treatment. In the Velcade group, suppression of at least 2 classes of immunoglobulins was significantly related to poorer survival in terms of both OS and PFS. In the non-velcade group, suppression of immunoglobulins showed no significant relationship with OS or PFS. Conclusions: For cases treated with Velcade, suppression of 2 types of immunoglobulins was related to poorer outcomes. Based on the results of the current study, it seemsed that immunoglobulin suppression was a predictive factor rather than a prognostic one. More studies with a larger sample size should be conducted to assess the outcome of patients treated with Velcade and severely suppressed immunoglobulins.

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“…Polyclonal IgG, IgA, and IgM immunoglobulins are often decreased in sera of patients with multiple myeloma (MM) due to an increased catabolism and a decreased biosynthesis (1,2). It is a matter of debate whether the extent of polyclonal IgG, IgA, and IgM hypo-g-globulinemia has a prognostic significance in MM at diagnosis or predicts development of active MM in monoclonal gammopathy of undetermined significance (MGUS).…”

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confidence: 99%

Polyclonal Immunoglobulin E Levels Are Correlated with Hemoglobin Values and Overall Survival in Patients with Multiple Myeloma

Matta

Battaglio²,

DiBello

et al. 2007

Clinical Cancer Research

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Purpose: Polyclonal IgG, IgA, and IgM immunoglobulins are often decreased in sera of patients with multiple myeloma (MM), whereas very few data are available on polyclonal IgE levels. We have determined IgE levels in a large series of MM patients at diagnosis and subjects with monoclonal gammopathy of undetermined significance (MGUS) and correlated IgE levels with survival and prognostic factors in MM. Experimental Design: IgE were determined with a commercially available ELISA kit in 201MM patients at diagnosis, 144 subjects with MGUS, and 77 age-matched controls. Results: IgE levels progressively decreased from controls to MGUS and from MGUS to MM (P = 0.001). MM patients with IgE levels of >11.5 IU/mL (median) had a better survival than patients with IgE of <11.5 IU/mL (P = 0.048). The difference was even more significant when MM patients were divided according to clinical cutoff values. Patients with elevated IgE levels (>100 IU/mL) had from 2 to 3 years longer survival than those with low (<10 IU/mL) or intermediate values (10-100 IU/mL; P < 0.01). IgE levels were positively and negatively correlated with hemoglobin (P = 0.006) and h2-microglobulin levels (P = 0.007), respectively. Univariate and multivariate analyses confirmed that high IgE levels are positive predictors of overall survival (P = 0.03 and 0.08, respectively) and strongly correlated with hemoglobin values. Polyclonal IgG, IgA, and IgM immunoglobulins are often decreased in sera of patients with multiple myeloma (MM) due to an increased catabolism and a decreased biosynthesis (1, 2). It is a matter of debate whether the extent of polyclonal IgG, IgA, and IgM hypo-g-globulinemia has a prognostic significance in MM at diagnosis or predicts development of active MM in monoclonal gammopathy of undetermined significance (MGUS). By contrast, very little is known on serum levels of polyclonal IgE (2 -4). In normal subjects, IgE synthesis is dependent on several factors, including the intrinsic properties and dose of antigen, the route of antigen delivery, the release of interleukin-4 from dendritic cells favoring the differentiation of naive Th 0 cells into Th 2 cells, the release of interleukin-4 and interleukin-13 from Th 2 cells, and the costimulatory interactions mediated by CD40/CD40 ligand between B and T cells (5 -9). As a result, total IgE levels are highly variable in general population, depending on many factors, such as age, gender, race, atopy, genetics, immune status, season of the year, tobacco smoke, and concomitant diseases (10 -15). Plotting the frequency distribution of IgE levels in a sample population on an arithmetic scale results in an overall distribution strongly skewed toward low values, with an isolated peak of very high IgE values. Replotting the same data on a logarithmic scale produces a Gaussian distribution (10, 11).Our interest on polyclonal IgE in MM originated from the immune monitoring of a group of patients treated at our institution with autologous idiotype vaccines and granulocyte macrophage colony-stim...

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Suppression of polyclonal immunoglobulins in multiple myeloma: Relationship to the staging and other manifestations at diagnosis

Cited by 60 publications

References 16 publications

Severe deficiency of B lymphocytes in peripheral blood from multiple myeloma patients.

Severe deficiency of B lymphocytes in peripheral blood from multiple myeloma patients.

Role of Suppressed Immunoglobulins in Outcome of Patients With Multiple Myeloma

Polyclonal Immunoglobulin E Levels Are Correlated with Hemoglobin Values and Overall Survival in Patients with Multiple Myeloma

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