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

Jean Harb (1, 2, 3) , Nicolas Mennesson (1) , Cassandra Lepetit (1) , Maeva Fourny (1) , Margaux Louvois (1) , Adrien Bosseboeuf (1) , Sophie Allain-Maillet (1) , Olivier Decaux (4) , Caroline Moreau (5) , Anne Tallet (6) , Eric Piver (7, 8) , Philippe Moreau (9) , Valéry Salle (10) , Edith Bigot-Corbel (1, 3) , Sylvie Hermouet (1, 9)

1 CRCINA-ÉQUIPE 16 - Molecular Mechanisms of Chronic Inflammation in Hematological Diseases
2 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
3 Laboratoire de Biochimie [Nantes]
4 Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes]
5 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
6 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
7 Laboratoire de Biochimie [CHRU Tours]
8 MAVIVHe - Morphogénèse et antigénicité du VIH, des Virus des Hépatites et Emergents
9 Service d'Hématologie [Nantes]
10 CHU Amiens-Picardie

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.

Mots clés: poliovirus; coxsackievirus; monoclonal gammopathy; MGUS; multiple myeloma; monoclonal immunoglobulin; infection; pathogen; antigen specificity

Domaines: Cancer

Jean Harb, Nicolas Mennesson, Cassandra Lepetit, Maeva Fourny, Margaux Louvois, et al.. Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens. Cells, 2021, 10 (2), pp.438. ⟨10.3390/cells10020438⟩. ⟨inserm-03148367⟩