Major low-energy trauma results in non-specific immunoglobulin generation without evidence for specific autoantibody production: A prospective cohort study

Scand J Immunol. 2024 Jun;99(6):e13368. doi: 10.1111/sji.13368. Epub 2024 Mar 25.

Abstract

Cellular debris resulting from large trauma might overwhelm the scavenger mechanisms and lead to autoimmune reactions. We analysed whether a major well-defined trauma in humans induces laboratory signs of transient autoimmunity in the months after the insult. We included 50 patients with pertrochanteric femur fracture undergoing intramedullary nail osteosynthesis in a prospective cohort study and followed them at 3-4 days, 6 weeks, 12 weeks and 12 months postoperatively. By standard techniques, we assessed levels of total immunoglobulins, anti-nuclear antibodies (ANA), anti-cardiolipin antibodies, anti-dsDNA antibodies and anti-C1q antibodies, as well as antibodies against cytomegalovirus (CMV) as a control. Blood leukocyte differential and lymphocyte subpopulations were determined at baseline and in the first two postoperative samples. The mean age of the patients reached 80.1 years, and 23 (46%) completed all visits. Serum concentrations of total IgG, IgM and IgA increased at all follow-up time points. The ANA fluorescence light intensity units increased at 12 weeks and 12 months postoperatively (p < 0.0001), but the proportion of ANA-positive patients did not change (35%). The values of anti-C1q mildly increased at all follow-up visits, but not the ratio to total IgG. Anti-dsDNA remained negative in all patients, and anti-cardiolipin IgG/IgM antibodies did not change. Anti-CMV IgG antibodies increased significantly at all follow-up visits, without change in the ratio to total IgG. Flow cytometry showed an increased proportion of B-cells 3-4 days postoperatively. In conclusion, major musculoskeletal trauma in elderly patients induces a generalized non-specific increase in immunoglobulin production without laboratory signs for enhanced systemic autoimmunity.

Keywords: ANA; CARS; anti‐nuclear antibodies; apoptosis; autoimmunity; cell death; compensatory anti‐inflammatory response syndrome; efferocytosis; immunoglobulins; necrosis; surgery; systemic autoantibodies; trauma.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Antinuclear / blood
  • Antibodies, Antinuclear / immunology
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • Autoimmunity
  • Cohort Studies
  • Complement C1q / immunology
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulins / blood
  • Male
  • Prospective Studies

Substances

  • Autoantibodies
  • Antibodies, Antinuclear
  • Immunoglobulin G
  • Complement C1q
  • Immunoglobulin M
  • Immunoglobulins