Enrichment of malondialdehyde-acetaldehyde antibody in the rheumatoid arthritis joint

Ted R Mikuls, Michael J. Duryee, Rafid Rahman, Daniel R Anderson, Harlan R. Sayles, Andrew Hollins, Kaleb D Michaud, Frederick Wolfe, Geoffrey E. Thiele, Jeremy Sokolove, William H. Robinson, Nithya Lingampalli, Anthony P. Nicholas, Geoffrey A Talmon, Kaihong Su, Matthew C Zimmerman, Lynell Warren Klassen, Geoffrey Milton Thiele

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Objective: To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA.

Methods: Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry.

Results: Circulating and SF anti-MAA antibody concentrations were higher in RA vs OA by 1.5- to 5-fold. IgG (P < 0.001), IgM (P = 0.006) and IgA (P = 0.036) anti-MAA antibodies were higher in paired RA SF than serum, differences not observed for total immunoglobulin, RF or ACPA. In RA synovial tissues, co-localization of MAA with citrulline and CD19+ or CD27+ B cells was demonstrated and was much higher in magnitude than MAA or citrulline co-localization with T cells, monocytes, macrophages or dendritic cells (P < 0.01).

Conclusion: Anti-MAA antibodies are present in higher concentrations in the RA joint compared with sera, a finding not observed for other disease-related autoantibodies. Co-localization of MAA and citrulline with mature B cells, coupled with the local enrichment of anti-MAA immune responses, implicates MAA-adduct formation in local autoantibody production.

Original languageEnglish (US)
Pages (from-to)1794-1803
Number of pages10
JournalRheumatology (Oxford, England)
Volume56
Issue number10
DOIs
StatePublished - Oct 1 2017

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Keywords

  • anti-citrullinated protein antibody (ACPA)
  • autoimmunity
  • malondialdehyde–acetaldehyde adducts
  • oxidative stress
  • rheumatoid arthritis
  • synovial fluid

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

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