Autoantibodies to human nuclear lamin B2 protein: Epitope specificity in different autoimmune diseases

José Brito, Giuseppe Biamonti, Roberto Caporali, Carlomaurizio Montecucco

Research output: Contribution to journalArticle

Abstract

The nuclear lamina of mammalian cells consists of three major proteins, lamins A, C, and B, and a fourth minor protein, lamin B2. Lamins belong to the family of intermediate filaments and are highly similar both in structure and primary sequence. They are organized in three well-defined domains: 1) a central α-helical rod, which is a secondary structure shared by all types of intermediate filaments, formed by three α-helices (coils 1A, 1B, and 2) and surrounded by 2) an amino-terminal head and 3) a carboxyl-terminal tail. Autoantibodies toward major lamin have been described previously in sera from patients with different autoimmune diseases. We chose an epitope mapping approach to further characterize the autoimmune response to nuclear lamin. Different lamin B2 domains were expressed as fusion proteins with the glutathione S-transferase and then used in immunoblotting experiments to analyze sera from patients with autoimmune diseases (chronic active hepatitis, SLE, rheumatoid arthritis, and polymyalgia rheumatica) and from healthy subjects. At a 1:1000 dilution, none of the control sera recognized any of the recombinant polypeptides. Conversely, reactive sera were present in all groups of patients. The ability to recognize a protein domain seemed to differ with the pathology. Most chronic active hepatitis sera were reactive to two or more lamin domains and reacting SLE sera always gave positive signals to coil 2 and/or coil 1B. Coil 2 was preferentially recognized by rheumatoid arthritis sera. Polymyalgia rheumatica sera differed from all of the others because of their low reactivity to the rod domain and preference for the C terminus, a lamin-specific domain.

Original languageEnglish
Pages (from-to)2268-2277
Number of pages10
JournalJournal of Immunology
Volume153
Issue number5
Publication statusPublished - Sep 1 1994

ASJC Scopus subject areas

  • Immunology

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