Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Bosseboeuf, Adrien; Feron, Delphine; Tallet, Anne; Rossi, Cédric; Charlier, Cathy; Garderet, Laurent; Caillot, Denis; Moreau, Philippe; Cardó-Vila, Marina; Pasqualini, Renata; Arap, Wadih; Nelson, Alfreda D.; Wilson, Bridget S.; Perreault, Hélène; Piver, Éric; Weigel, Pierre; Girodon, François; Harb, Jean; Bigot‐Corbel, Edith; Hermouet, Sylvie

doi:10.1172/jci.insight.95367

Cited by 38 publications

(64 citation statements)

References 50 publications

(57 reference statements)

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“…Therefore, the prevention and treatment of the virus in newly diagnosed patients with MM is essential. If an underlying chronic infection is cleared up early enough in disease progression, it could offer the possibility of preventing MGUS transition to SM and MM in the first place [20]. In addition, we agree with the point that newly diagnosed patients with MM should be screened for serum hepatitis B viral markers universally in HBV endemic areas [22].…”

Section: Discussionsupporting

confidence: 57%

“…Through molecular analysis, a recent study [19] displayed significant EBV DNA in malignant plasma cell disorders, especially in MM and MGUS patients. Bosseboeuf et al [20] demonstrated that EBV was the most frequent target of purified monoclonal IgG produced by patients with MGUS or MM. They considered that chronic stimulation by infectious Ag may promote MGUS and MM.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study [18], the risk of developing a bacterial infection increased 7-fold and viral infections 10-fold in MM patients compared with matched controls. Previous studies have also indicated that Epstein-Barr virus (EBV) infection was more likely with patients with MM and monoclonal gammopathy of undetermined significance (MGUS) [19,20]. In addition, higher hepatitis B virus (HBV) infection rates have been found in MM patients [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of infection in newly diagnosed multiple myeloma patients: Risk factors and main characteristics

Lin

Shen

Zhou

et al. 2019

Preprint

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Background: Infection is a leading cause of morbidity and death in patients with multiple myeloma (MM). The increased susceptibility to infection is complicated and multifactorial. However, no studies have explored the spectrum and risk factors of infections in newly diagnosed MM patients at the first admission. This cross-sectional study aimed to provide ideas for the assessment, prevention and treatment of infection in newly diagnosed MM patients when admitted for the first time. Methods: Retrospectively, the data from electronic medical records for 161 patients newly diagnosed with MM from May 2013 to December 2018 were analysed. All the information was collected at the time of admission, and the patients had received no antineoplastic therapy previously. Independent risk factors of infection in multiple myeloma were determined by univariate and multivariate analysis. Results: Newly diagnosed patients with MM were highly susceptible to viruses (43.9%), especially Epstein-Barr virus (EBV) (24.4%) and hepatitis B virus (HBV) (17.1%). Advanced stage (ISS stage III, P =0.040), more severe anaemia (Hb<90 g/L, P =0.044) and elevated CRP (>10 mg/L, P =0.006) were independent risk factors for infection. Moreover, infections represented a major survival threat to patients with newly diagnosed MM ( P = 0.033), and the existence of risk factors for infection was significantly correlated with poor prognosis ( P = 0.011), especially ISS stage III ( P =0.008) and lower haemoglobin level ( P =0.039). Conclusions: Newly diagnosed MM patients are highly susceptible to viruses. Advanced ISS stage, more severe anaemia and the elevation of CRP are independent risk factors of infection, which also have a strong impact on prognosis. Our results suggest that viral infection should be taken into account if antibacterial drugs are not effective, and the prevention of infection and improvement of prognosis should be paid more attention in newly diagnosed patents with advanced stage and more severe anaemia.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessment of infection in newly diagnosed multiple myeloma patients: Risk factors and main characteristics

Lin

Shen

Zhou

et al. 2019

Preprint

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“…Over time, the chronically stimulated lineage is at the origin of an increased risk of genetic alteration leading to clonality and malignant transformation. To support this pathogenic process in MGUS and myeloma, we recently reported that six infectious pathogens, including carcinogenic viruses [EBV, HCV, Herpes simplex virus (HSV)] and bacteria ( H. pylori ), are the targets of ~23% of purified mc IgG from MGUS, SM, and MM patients ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory State in Monoclonal Gammopathy of Undetermined Significance and in Multiple Myeloma Is Characterized by Low Sialylation of Pathogen-Specific and Other Monoclonal Immunoglobulins

et al. 2017

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Multiple myeloma (MM) and its pre-cancerous stage monoclonal gammopathy of undetermined significance (MGUS) allow to study immune responses and the chronology of inflammation in the context of blood malignancies. Both diseases are characterized by the production of a monoclonal immunoglobulin (mc Ig) which for subsets of MGUS and MM patients targets pathogens known to cause latent infection, a major cause of inflammation. Inflammation may influence the structure of both polyclonal (pc) Ig and mc Ig produced by malignant plasma cells via the sialylation of Ig Fc fragment. Here, we characterized the sialylation of purified mc and pc IgGs from 148 MGUS and MM patients, in comparison to pc IgGs from 46 healthy volunteers. The inflammatory state of patients was assessed by the quantification in serum of 40 inflammation-linked cytokines, using Luminex technology. While pc IgGs from MGUS and MM patients showed heterogeneity in sialylation level, mc IgGs from both MGUS and MM patients exhibited a very low level of sialylation. Furthermore, mc IgGs from MM patients were less sialylated than mc IgGs from MGUS patients (p < 0.01), and mc IgGs found to target an infectious pathogen showed a lower level of sialylation than mc IgGs of undetermined specificity (p = 0.048). Regarding inflammation, 14 cytokines were similarly elevated with a p value < 0.0001 in MGUS and in MM compared to healthy controls. MM differed from MGUS by higher levels of HGF, IL-11, RANTES and SDF-1-α (p < 0.05). MGUS and MM patients presenting with hyposialylated pc IgGs had significantly higher levels of HGF, IL-6, tumor necrosis factor-α, TGF-β1, IL-17, and IL-33 compared to patients with hyper-sialylated pc IgGs (p < 0.05). In MGUS and in MM, the degree of sialylation of mc and pc IgGs and the levels of four cytokines important for the anti-microbial response were correlated, either positively (IFN-α2, IL-13) or negatively (IL-17, IL-33). Thus in MGUS as in MM, hyposialylation of mc IgGs is concomitant with increased levels of cytokines that play a major role in inflammation and anti-microbial response, which implies that infection, inflammation, and abnormal immune response contribute to the pathogenesis of MGUS and MM.

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“…Finally, Bosseboeuf et al reported that some infectious agents, including H. pylori , may be the target of monoclonal IgG in patients with monoclonal gammopathy of undetermined significance and multiple myeloma, possibly explaining the onset or progression of this hematologic condition …”

Section: Hematologic Diseasesmentioning

confidence: 99%

Helicobacter pylori and extragastric diseases

2018

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Many studies have been performed in the last year concerning the potential role of Helicobacter pylori in different extragastric diseases, reinforcing the idea that specific microorganisms may cause diseases even far from the primary site of infection. While the role of H. pylori on idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency has been well established, there is a growing interest in other conditions, such as cardiovascular, neurologic, dermatologic, obstetric, immunologic, and metabolic diseases. Concerning neurologic diseases, there is a great interest in cognitive impairment and neurodegeneration. The aim of this review was to summarize the results of the most relevant studies published over the last year on this fascinating topic.

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Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Cited by 38 publications

References 50 publications

Assessment of infection in newly diagnosed multiple myeloma patients: Risk factors and main characteristics

Assessment of infection in newly diagnosed multiple myeloma patients: Risk factors and main characteristics

Pro-inflammatory State in Monoclonal Gammopathy of Undetermined Significance and in Multiple Myeloma Is Characterized by Low Sialylation of Pathogen-Specific and Other Monoclonal Immunoglobulins

Helicobacter pylori and extragastric diseases

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