Identification of a unique anti-Ro60 subset with restricted serological and molecular profiles

Clin Exp Immunol. 2021 Jan;203(1):13-21. doi: 10.1111/cei.13508. Epub 2020 Sep 17.

Abstract

Anti-Ro60 is one of the most common and clinically important serum autoantibodies that has a number of diagnostic and predictive capabilities. Most diagnostic laboratories report this simply as a qualitative positive/negative result. The objective of this study was to examine the clinical and serological relevance of a novel subset of anti-Ro60 in patients who display low levels of anti-Ro60 (anti-Ro60low ). We retrospectively identified anti-Ro60 sera during a 12-month period at a major immunopathology diagnostic laboratory in Australia. These all were anti-Ro60-precipitin-positive on the diagnostic gold standard counter-immuno-electrophoresis (CIEP). Lineblot immunoassay was used to stratify patients into either anti-Ro60low or anti-Ro60high subsets. We compared the medical and laboratory parameters associated with each group. Enzyme-linked immunosorbent assay (ELISA) and mass spectrometry techniques were used to analyse the serological and molecular basis behind the two subsets. Anti-Ro60low patients displayed less serological activity than anti-Ro60high patients with less intermolecular spreading, hypergammaglobulinaemia and less tendency to undergo anti-Ro60 isotype-switching than anti-Ro60high patients. Mass spectrometric typing of the anti-Ro60low subset showed restricted variable heavy chain subfamily usage and amino acid point mutations. This subset also displayed clinical relevance, being present in a number of patients with systemic autoimmune rheumatic diseases (SARD). We identify a novel anti-Ro60low patient subset that is distinct from anti-Ro60high patients serologically and molecularly. It is not clear whether they arise from common or separate origins; however, they probably have different developmental pathways to account for the stark difference in immunological maturity. We hence demonstrate significance to anti-Ro60low and justify accurate detection in the diagnostic laboratory.

Keywords: anti-Ro60; antibodies; autoantibodies; diagnostics; laboratory medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antinuclear* / blood
  • Antibodies, Antinuclear* / immunology
  • Australia
  • Autoantigens* / blood
  • Autoantigens* / immunology
  • Autoimmune Diseases* / blood
  • Autoimmune Diseases* / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • K562 Cells
  • RNA, Small Cytoplasmic* / blood
  • RNA, Small Cytoplasmic* / immunology
  • Ribonucleoproteins* / blood
  • Ribonucleoproteins* / immunology

Substances

  • Antibodies, Antinuclear
  • Autoantigens
  • RNA, Small Cytoplasmic
  • RO60 protein, human
  • Ribonucleoproteins