scholarly journals Two Cases of Heavy Chain MGUS

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Jan Van Keer ◽  
Björn Meijers ◽  
Michel Delforge ◽  
Gregor Verhoef ◽  
Koen Poesen
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Heavy Chain ◽  
Monoclonal Gammopathy ◽  
Rare Variants ◽  
Light Chains ◽  
B Cell Lymphomas ◽  
Heavy Chains ◽  
Heavy Chain Diseases

Heavy chain diseases are rare variants of B-cell lymphomas that produce one of three classes of immunoglobulin heavy chains, without corresponding light chains. We describe two patients with asymptomatic heavy chain monoclonal gammopathy. The first patient is a 51-year-old woman with alpha paraprotein on serum immunofixation. The second case is a 46-year-old woman with gamma paraprotein on urine immunofixation. Neither patient had corresponding monoclonal light chains. Workup for multiple myeloma and lymphoma was negative in both patients. These two cases illustrate that heavy chain monoclonal gammopathy can exist in the absence of clinically apparent malignancy. Only a few reports of “heavy chain MGUS” have been described before. In the absence of specialized guidelines, we suggest a similar follow-up as for MGUS, while taking into account the higher probability of progression to lymphoma than to myeloma.

scholarly journals Immunoglobulin heavy chains are sufficient to determine most B cell clonal relationships1

2019 ◽  
Author(s):  
Julian Q. Zhou ◽  
Steven H. Kleinstein
Keyword(s):  
B Cell ◽  
High Throughput ◽  
Heavy Chain ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Light Chains ◽  
Heavy Chains ◽  
Computational Inference ◽  
Cell Clonal Expansion

AbstractB cell clonal expansion is vital for adaptive immunity. High-throughput B cell receptor (BCR) sequencing enables investigating this process, but requires computational inference to identify clonal relationships. This inference usually relies on only the BCR heavy chain, as most current protocols do not preserve heavy:light chain pairing. The extent to which paired light chains aids inference is unknown. Using human single-cell paired BCR datasets, we assessed the ability of heavy chain-based clonal clustering to identify clones. Of the expanded clones identified, <20% grouped cells expressing inconsistent light chains. Heavy chains from these misclustered clones contained more distant junction sequences and shared fewer V segment mutations than the accurate clones. This suggests that additional heavy chain information could be leveraged to refine clonal relationships. Conversely, light chains were insufficient to refine heavy chain-based clonal clusters. Overall, the BCR heavy chain alone is sufficient to identify clonal relationships with confidence.

B-cell receptors and heavy chain diseases: guilty by association?

Blood ◽  
2011 ◽  
Vol 117 (26) ◽  
pp. 6991-6998 ◽  
Author(s):  
Daniel Corcos ◽  
Michael J. Osborn ◽  
Louise S. Matheson
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Selective Advantage ◽  
Heavy Chains ◽  
Aggregation Effect ◽  
Heavy Chain Diseases ◽  
Self Aggregation ◽  
Gene Alterations

Heavy chain diseases (HCDs) are B-cell proliferative disorders characterized by the production of monoclonal, incomplete, immunoglobulin (Ig) heavy chains (HCs) without associated light chains (LCs). These abnormal HCs are produced as a consequence of HC gene alterations in the neoplastic B cells. HC gene alterations will also impact on surface HC, which is part of the B-cell receptor (BCR), a crucial player in lymphocyte activation by antigen. The selective advantage conferred to mutant cells by abnormal BCR without an antigen-binding domain may be explained by activation of ligand-independent signaling, in analogy to what has been shown for mutated oncogenic growth factor receptors. Here we review data obtained from mouse models showing abnormal, constitutive activity of HCD-BCR, and we discuss the possible mechanism involved, namely, aberrant spontaneous self-aggregation. This self-aggregation might occur as a consequence of escape from the chaperone immunoglobulin binding protein (BiP) and from the anti-aggregation effect of LC association. The concept of misfolding-induced signaling elaborated here may extend to other pathologies termed conformational diseases.

scholarly journals HEAVY-CHAIN DISEASES AND MYELOMA-ASSOCIATED FANCONI SYNDROME: AN UPDATE

2018 ◽  
Vol 10 (1) ◽  
pp. 2018011 ◽  
Author(s):  
Roberto Ria ◽  
Franco Dammacco ◽  
Angelo Vacca
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Monoclonal Gammopathy ◽  
Fanconi Syndrome ◽  
Rare Complication ◽  
Immunoglobulin Heavy Chain ◽  
Mediterranean Area ◽  
Non Hodgkin Lymphoma ◽  
Heavy Chain Diseases ◽  
Stage Renal Disease

The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (α-HCD), IgG (γ-HCD), and IgM (μ-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and μ-HCDs are more rare and associated to a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain. These patients may occasionally be diagnosed with a monoclonal gammopathy of undetermined significance (MGUS). Fanconi syndrome, on the other hand, can be primary (inherited) or secondary (acquired). The only exception to this rule is the idiopathic form. Adult acquired Fanconi syndrome can be a rare complication of a monoclonal gammopathy. At diagnosis, most patients have a MGUS or smoldering multiple myeloma, with renal failure and evidence of osteomalacia. During follow-up, patients can develop end-stage renal disease. Chemotherapy provides little benefit on renal function.

scholarly journals Follow-up of IgD-κ multiple myeloma by monitoring free light chains and total heavy chain IgD: A case report

2016 ◽  
Vol 12 (3) ◽  
pp. 1884-1888
Author(s):  
Elena De Santis ◽  
Serena Masi ◽  
Iole Cordone ◽  
Francesco Pisani ◽  
Cecilia Zuppi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Heavy Chain ◽  
Light Chains ◽  
Free Light Chains

Clinical and Biological Features of Biclonal Gammopathies. Review of 203 Cases

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5151-5151
Author(s):  
Olivier Decaux ◽  
Helene Leroy ◽  
Jean-Christophe Ianotto ◽  
Annie Ruelland ◽  
Lucienne Guenet ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Malignant Transformation ◽  
Monoclonal Gammopathy ◽  
Systemic Disease ◽  
Light Chains ◽  
Lymphoproliferative Diseases ◽  
Monoclonal Gammopathies ◽  
Biclonal Gammopathy ◽  
Monoclonal Component

Abstract Introduction: Biclonal gammopathies represent about 5% of clonal gammopathies. We describe the clinical and laboratory features of biclonal gammopathies identified in a French university hospital. Methods: Patients were selected by immunofixation registry of Biochemistry laboratory. Results: From 1987 to 2008, 203 biclonal gammapathies were identified. Patients were 113 men and 90 women. Median age was 72.0 years (35–95). Seventy eight patients (38.3%) had IgG and IgM components, 64 (31,9%) had two IgG, 24 (11,8%) had IgG and IgA, 23 (11,3%) had two IgM, 8 (3,9%) had IgM and IgA, 5 (2,4%) had two IgA, one (0.5%) had Ig G and IgD (0,5%). Of the 406 light chains, 260 (63,8%) were kappa, 146 (36.2%) were lambda. Eighty nine patients (44.1%) had two kappa light chains, 82 (40,2%) had both kappa and lambda and 32 (15,7%) had two lambda chains. Median gammaglobulin concentration was 13.3 g/L (3–59.9). The most frequent diagnosis was biclonal gammopathy of undeterminated significance (BGUS) in 123 patients (60.6%). Others patients could be divided into 3 groups. Forty seven patients (23.1%) had lymphoproliferative diseases, including Waldenström’s macroglobulinemia (21 cases), non Hodgkin lymphoma (20), chronic lymphocytic leukaemia (6). Eighteen (8.87%) had multiple myeloma. For the last 15 patients (7.4%), biclonal gammopathy was associated with a non lymphoid hemopathy or with systemic disease. Biclonal gammopathy was identified in 12 patients already known to have a monoclonal gammopathy (7 monoclonal gammopathy of undetermined significance-MGUS, 3 myeloma and 2 Waldenström’s macroglobulinemia). In 3 cases, the finding of the second monoclonal component was concurrent to the diagnosis of a MGUS malignant transformation to myeloma (2 cases) or Waldenström’s macroglobulinemia (1 case). Median follow-up was 23 months (12 to 252 months) for the 123 patients with BGUS. In 4 cases (3.2%) a malignant transformation was observed. Three patients developed a multiple myeloma (time to transformation was 2 years for one and 4 years for the 2 others) and one patient Waldenström’s macroglobulinemia (6 years). Conclusions: As for monoclonal gammopathies, BGUS represent the most frequent diagnosis. However, in contrast to monoclonal gammopathies, biclonal gammopathies are more frequently associated with lymphoproliferative diseases than with multiple myeloma. The apparition of a second monoclonal component during follow up of MGUS could be associated with malignant transformation and should lead to new evaluation. The risk of transformation of BGUS seems similar to MGUS but further studies are necessary to compare the evolution of MGUS and BGUS.

Rocket Immunoselection for Detection of Heavy-Chain Diseases

1974 ◽  
Vol 20 (10) ◽  
pp. 1292-1294 ◽  
Author(s):  
D S J Gale ◽  
J M B Versey ◽  
John R Hobbs
Keyword(s):  
Heavy Chain ◽  
Light Chains ◽  
Lower Section ◽  
Lower Region ◽  
Heavy Chains ◽  
Heavy Chain Diseases ◽  
Heavy Chain Disease

Abstract A method is described that allows heavy-chain disease proteins to be simply detected. The sample is electrophoresed in an agarose plate containing kappa and lambda antisera in the lower section, and the relevant heavy-chain antisera in the upper section. Light chains and immunoglobulins containing light chains are precipitated in the lower region. Free "heavy chains" migrate into the upper region, where they are precipitated as a separate rocket. The method is quick, sensitive, and requires little antiserum.

scholarly journals Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2107-2111
Author(s):  
JR Berenson ◽  
A Lichtenstein ◽  
S Hart ◽  
D Palomares ◽  
RA Miller
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Similar Frequency ◽  
Murine Monoclonal Antibodies ◽  
Undetermined Significance

Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

scholarly journals Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2107-2111 ◽  
Author(s):  
JR Berenson ◽  
A Lichtenstein ◽  
S Hart ◽  
D Palomares ◽  
RA Miller
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Similar Frequency ◽  
Murine Monoclonal Antibodies ◽  
Undetermined Significance

Abstract Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

Association Between Immunoparesis and a Skewed Free Light Chain (FLC) Ratio: A New Prognostic Factor Of Progression from MGUS To Multiple Myeloma?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5314-5314
Author(s):  
Michele Pizzuti ◽  
Alberto Santagostino ◽  
Giuseppina Smaldore ◽  
Ida Chitarrelli ◽  
Domenico Vertone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Light Chains ◽  
Molecular Events ◽  
Risk Of Progression ◽  
Two Parameters

Abstract Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3% of people older than 50 years and up to 10% in those older than 70; it is associated with a 1%/year risk of progression to Multiple Myeloma (MM). In recent years there have been improvements in risk stratification models (involving molecular markers) of this disorder, which have led to better understanding of the biology and probability of progression of MGUS. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. Free Lights Chains (FLC) ratio, plasma cells immunophenotype and DNA aneuplody are now important parameters of progression, in addition to the already known prognostic factors (immunoparesis, type and amount of the monoclonal component (MC). Recent data report immunoparesis and a skewed FLC ratio in 25% and 30%, respectively, of patients (pts) at diagnosis. In this study we evaluated the incidence of these two parameters in a cohort of 114 pts with MGUS, if they are associated and if their incidence is influenced by other parameters (time from diagnosis, type of Immunoglobulin (Ig) and/or light chains). The patients screened were 56 males and 58 females with a median age of 67 years (45-91). Median time from diagnosis to the time of observation was 3 years (0-21). The MC was IgA in 13 pts, IgG in 88, IgM in 13; 74 had a clonal Kappa (K) and 40 a lambda (L) light chain. K/L ratio was abnormal in 57 pts (50%). Immunoparesis was present in 60 pts (52,6%): 22 with a normal K/L ratio (38,5%) and 38 with an abnormal K/L ratio (66,6%) (p-0.004). In 18 pts two classes of Ig were involved. An association between the two parameters occurred in 39 pts (34,2%); it was more frequent in IgA MGUS (61,5%) than in IgG (31,8%) and IgM (23%); we did not observe any differences about immunoparesis between K MGUS (33,7%) and L MGUS (32,5%). The association between a skewed K/L ratio and immunoparesis was present in 25.4% of pts with time from diagnosis of less than 3 years and in 48,8% of pts with a longer time from diagnosis (p-0.04). Our new data confirm that immunoparesis is more frequent in pts with an abnormal K/L ratio. The association seems to be more frequent in case of IgA gammopathy; there are no differences between the two types of light chain. Our data also confirm that the longer is the time elapsed from diagnosis, the higher are the frequency of an abnormal K/L ratio and the incidence of immunoparesis, with a greater probability of association. We need still a larger number of pts with an adequate follow up to evaluate if the association between immunoparesis and abnormal K/L ratio has a prognostic value, although the higher frequency of association in the subset of pts with a longer time from diagnosis seems to contradict this hypothesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 438
Author(s):  
Jean Harb ◽  
Nicolas Mennesson ◽  
Cassandra Lepetit ◽  
Maeva Fourny ◽  
Margaux Louvois ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Coat Proteins ◽  
Chronic Stimulation ◽  
B Cell Epitopes ◽  
Monoclonal Immunoglobulins ◽  
Self Antigen ◽  
Coxsackievirus B1 ◽  
Undetermined Significance

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

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