Myeloma-Associated Paraprotein Directed against the HIV-1 p24 Antigen in an HIV-1-Seropositive Patient

Konrad, Robert J.; Kricka, Larry J.; Goodman, David B. P.; Goldman, J; Silberstein, Leslie E.

doi:10.1056/nejm199306243282505

Cited by 64 publications

(30 citation statements)

References 20 publications

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“…Moreover, the follow-up time of these studies is much less than the median of 10 years between detection of paraproteinemia and onset of plasma cell neoplasm seen in the general population. The high concentration, persistent paraproteins reported by Lefrère 68 and others (paraprotein concentrations of 65, 52 64, 67 43 63 and 37 61 g/l have been described) are much more likely to represent pre-malignant states, similar to MGUS in the general population. Conclusive proof, however, must come from long-term follow-up of MGUS-positive AIDS patients who are carefully screened for signs of B lineage neoplasms, particularly plasma cell malignancies.…”

Section: Gammopathy and Plasma Cell Tumors In Aidsmentioning

confidence: 81%

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Fiorino

Atac

1997

Leukemia

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We have identified by MEDLINE search the cases of gammaglobinopathy and plasma cell malignancy in HIV-positive patients reported in the English language literature. The average age at presentation among HIV-positive patients with plasma cell disorders is 33 years, far younger than the average age of presentation in the general population. Some of these patients present with transient paraproteinemias, while others have persistent paraproteins, which may or may not be associated with true plasma cell malignancies. In most cases in which it has been examined, the paraprotein contains high-titer anti-HIV activity. The presence of high-titer anti-HIV activity in the paraproteins of AIDS patients suggests that an antigen-driven process in response to HIV infection may contribute to the early development of plasma cell disorders in these patients. Recent work in plasma cell tumorigenesis has indicated that transformation at a single point in the B lymphocyte lineage can give rise to either lymphoma or myeloma, dependent upon environmental factors such as T cell function, which may be required for directing transformed lymphocytes from lymphoma and towards plasma cell differentiation. This may explain why B lineage oncogenesis in AIDS patients favors the development of lymphoma over that of myeloma.

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Section: Gammopathy and Plasma Cell Tumors In Aidsmentioning

confidence: 81%

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Fiorino

Atac

1997

Leukemia

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“…5 In another case, a patient developed a serum M-component with specificity for horse a 2 -macroglobulin 30 years after receiving passive serotherapy with horse antiserum to tetanus. 15 Even though few of these studies convincingly proved that the observed phenomena were indeed caused by binding of the respective paraprotein to its specific antigenic target (e.g., by ''reverse Western'' blotting and/or sequencing of the target antigen as done in this study), these selective observations are often cited to support a causal relationship between the development of an MGUS or MM clone and chronic antigenic stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…15 Even though few of these studies convincingly proved that the observed phenomena were indeed caused by binding of the respective paraprotein to its specific antigenic target (e.g., by ''reverse Western'' blotting and/or sequencing of the target antigen as done in this study), these selective observations are often cited to support a causal relationship between the development of an MGUS or MM clone and chronic antigenic stimulation. [1][2][3][4][5][16][17][18][19][20][21][22][23] Similarly, doubts are raised about the paraprotein-mediated reactions with antigens predicted by epitope reconstruction and reported in a recent paper, 24 because the reactions were observed at concentrations of the paraprotein-containing serum of only 1:2,500. In contrast to these reports, our first systematic studies 7,8 did not only convincingly prove the paraprotein-mediated reactivity against the identified antigens, it also revealed a broad spectrum of antigenic targets of paraproteins.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 To date, antigenic targets of paraproteins were discovered accidentally due to clinical symptoms caused by the paraprotein (e.g., chronic cold agglutinin disease or cryoglobulinemia 3 or bleeding disorder 4 ), because of interference of the paraprotein with laboratory tests ordered for the clinical work-up of the patient (e.g., HIV-1 p24 antigen in an HIV-infected patient with myeloma 5 ) and/or by screening paraproteins against predefined antigens (e.g., anti-streptolysin, anti-DNA, anti-IgG 3 ). One of the first systematic searches covering a broad spectrum of potential antigens used SEREX (serological identification of antigens by expression cloning) which allows for the systematic screening of putative antibody-antigen interactions, even if neither the antigen nor the antibody are known.…”

Section: Uiccmentioning

confidence: 99%

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A frequent target of paraproteins in the sera of patients with multiple myeloma and MGUS

Preuss

Pfreundschuh

Ahlgrimm

et al. 2009

Intl Journal of Cancer

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Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins might play a role in the pathogenesis of these neoplasms. We screened a human fetal brain-derived macroarray with the IgA or IgG containing sera of 192 consecutive MGUS and MM patients. Twenty-nine of 192 (15.1%) paraproteins reacted with paratarg-7, a protein of unknown function which is expressed in all human tissues. Paratarg-7 reactivity was similarly frequent among IgA and IgG paraproteins, but all paratarg-7 reactive IgG paraproteins belonged to the IgG3 subtype with 24/57 IgG3 (42.1%) paraproteins displaying this specificity. Sequence analysis of paratarg-7 derived from patients having a paraprotein with specificity for paratarg-7 revealed no differences to paratarg-7 derived from patients with paraproteins of other specificities or healthy controls, excluding mutations or polymorphisms as a reason for its autoimmunogenicity. Similarly, Western-blot analysis showed identical bands for paratarg-7 derived from patients and controls. The above-random frequency of paratarg-7 as a paraprotein target suggests that paratarg-7 might be involved in the development of the respective clonal proliferations. The identification of paratarg-7 as an antigenic target enables the more detailed analysis of tumor-host interactions in these patients and their role in the pathogenesis of MM and MGUS. ' 2009 UICC

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“…5 In another case, a patient developed a serum M-component with specificity for horse a 2 -macroglobulin 30 years after receiving passive serotherapy with horse antiserum to tetanus. 8 Even though few of these studies convincingly proved that the observed phenomena were indeed caused by binding of the respective paraprotein to its specific antigenic target (e.g., by ''reverse Western'' blotting or sequencing of the target antigen as done in this study), these selective observations are often cited to support a causal relationship between the development of an MGUS or MM clone and chronic antigenic stimulation.…”

Section: Demonstration Of Paraprotein-mediated Reactivitymentioning

confidence: 99%

Identification of antigenic targets of paraproteins by expression cloning does not support a causal role of chronic antigenic stimulation in the pathogenesis of multiple myeloma and MGUS

Preuss

Held

Kubuschok

et al. 2007

Intl Journal of Cancer

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Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins have been suggested to play an important role as growth stimulators in the pathogenesis of these neoplasms. To identify such targets, we screened cDNA libraries from human testis, lung and breast cancer, bovine and porcine muscle and wheat germ for reactivity with paraproteins in the sera from 115 patients with MGUS and MM. Of >6 3 10 8 paraprotein-antigen interactions screened, an IgA paraprotein from a female patient bound to sperm-specific cylicin-2, and 3 IgG paraproteins bound to tripeptidyl-peptidase-II (TPP-2), insulin-like growth-factor binding-protein-2 (IGFBP-2) and porcine kinesin. Specificity was confirmed by reverse Western blots using recombinant antigens. The broad spectrum of auto-, allo-and heteroantigens as targets of human paraproteins in patients without signs of chronic antigenic stimulation renders a causal role of the antigenic stimulus in the pathogenesis of MGUS and MM unlikely. ' 2007 Wiley-Liss, Inc.

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Myeloma-Associated Paraprotein Directed against the HIV-1 p24 Antigen in an HIV-1-Seropositive Patient

Cited by 64 publications

References 20 publications

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Paraproteinemia, plasmacytoma, myeloma and HIV infection

A frequent target of paraproteins in the sera of patients with multiple myeloma and MGUS

Identification of antigenic targets of paraproteins by expression cloning does not support a causal role of chronic antigenic stimulation in the pathogenesis of multiple myeloma and MGUS

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