Characterization of immunoglobulin variable regions of two human pathogenic monoclonal cryocrystalglobulins

Valentina Navazza, Silvia Gabba, Andrea Alfieri, Sofia Giorgetti, Loredana Marchese, Giovanni Palladini, Andrea Mattevi, Edoardo Ascari, Roberto Caporali, Carlomaurizio Montecucco, Giampaolo Merlini, Vittorio Perfetti

Research output: Contribution to journalArticlepeer-review


Cold-precipitating monoclonal immunoglobulins can rarely aggregate in form of crystals (cryocrystalglobulins) and cause serious clinical manifestations. The structural basis underlying this phenomenon remains to be defined. This study was undertaken to provide the first characterization of the heavy (VH) and light chain (VL) variable regions of two human pathogenic cryocrystalglobulins. The immunoglobulins used different heavy and light chain constant regions and germline gene fragments, underwent high degrees of somatic hypermutation, and showed distributions of replacement and silent nucleotide changes suggestive of antigenic selection. Primary sequences analyses and computer-generated modeling identified a positive charge and the introduction of unusual hydrophobic residues in exposed areas of VH and VL. In particular, a rare replacement of a polar residue with proline is shared at the beginning of the VH complementarity-determining region 2, and this residue might be involved in intermolecular contacts.

Original languageEnglish
Pages (from-to)1519-1524
Number of pages6
JournalMolecular Immunology
Issue number5
Publication statusPublished - Mar 2008


  • B-cell lymphoproliferative disorder
  • Cryocrystalglobulins
  • Immunoglobulin variable regions

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology


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