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

Abstract

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.

Immune response to a conserved enteroviral epitope of the major capsid VP1 protein is associated with lower risk of cardiovascular disease

“…In addition, high similarity was observed with VP1 N-termini of vaccine-derived polioviruses (VDPVs), namely VDPV3 (VDPV3/EST/Env2008 (GenBank: KC784372.1, Figure 3a). Of note, analysing our MVA data we found that seroreactivity to the recently described peptide sequences PALTAVETG and PALTAAETG, derived of the VP1 proteins of human PV-1/3 and CV-B1/B3 viruses and also shared by many other picornaviruses, 42 did not differentiate MI cases from controls (Figure S7), further confirming the functional relevance of the G-I-X-D findings. Then, we used conventional ELISA method to measure IgG response in Estonia I cohort sera (n = 14; same samples as in Figure 2a) against VP1 of several enteroviral species, including coxsackieviruses B1, B3 and B5 and with reported cross-reactivity to poliovirus type 3.…”

Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

“…Previous reports have suggested an association between MGUS, MM and infection. In particular, we and others showed that at least one-third of MGUS and MM cases present with a monoclonal Ig that targets an infectious pathogen, including HCV ( 17 , 22 , 23 , 26 – 28 ). The recent in vivo demonstration that chronic antigen stimulation can lead to emergence of clonal plasma cells supports the role of chronic infection in the development of subsets of MGUS and MM ( 15 ).…”

Editorial: The Role of Microorganisms in Multiple Myeloma

“…Presently, the infection which drives MGUS or MM can be identified in 60% MGUS patients and 33% of MM patients ( 9 , 10 ). As disease progression has been associated with dysbiosis in mice ( 14 ), Jasiński et al.…”

“…Although MGUS is most often asymptomatic, patients may present with renal, neurological or skin symptoms of various severity (for instance, monoclonal gammopathies of renal significance (MGRS)) (6)(7)(8). Associations between MGUS and autoimmune disorders, infection and recently, gut microbiota, are established (3,5,9,10,(14)(15)(16)(17)(18)(19)(20)(21)(22). Importantly, several groups demonstrated that monoclonal Ig from MGUS and MM patients specifically target either a self-antigen (including myelin-associated glycoprotein (MAG), glucosylsphingosine (GlcSph, in 13-15% MGUS/MM cases), other gangliosides, different membrane components) or an antigen from an infectious pathogen (including HCV, HBV, HIV, EBV, other Herpesviruses, Helicobacter pylori, or Enteroviruses, in 60% MGUS and 33% MM).…”

“…MM is always preceded by a benign stage, called monoclonal gammopathy of undetermined significance (MGUS) ( 2 ). Recent studies suggested association of MGUS and MM with autoimmunity and with various microorganisms, including hepatitis C virus (HCV), human immunodeficiency virus (HIV), Epstein Barr virus (EBV), and other infectious pathogens ( 3 – 10 ). Indeed, chronic stimulation by self- or infectious antigens is recognized as an initial pathogenic event leading to chronic inflammation, cell proliferation, acquisition of genetic alterations, and cancer.…”