High titer anti-basement membrane antibodies in a subset of patients with pediatric systemic lupus erythematosus

Am J Nephrol. 2015;41(3):241-7. doi: 10.1159/000381965. Epub 2015 Apr 25.

Abstract

Background/aims: There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis.

Methods: Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE.

Results: MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients.

Conclusion: The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antibodies, Anti-Idiotypic / blood
  • Antibodies, Antinuclear / blood
  • Autoantibodies / blood*
  • Basement Membrane / immunology*
  • Biomarkers / blood*
  • Case-Control Studies
  • Child
  • DNA / immunology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / complications*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Nephritis / blood*
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Antinuclear
  • Autoantibodies
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • anti-IgG
  • DNA