TY - JOUR
T1 - Enrichment of malondialdehyde-acetaldehyde antibody in the rheumatoid arthritis joint
AU - Mikuls, Ted R
AU - Duryee, Michael J.
AU - Rahman, Rafid
AU - Anderson, Daniel R
AU - Sayles, Harlan R.
AU - Hollins, Andrew
AU - Michaud, Kaleb D
AU - Wolfe, Frederick
AU - Thiele, Geoffrey E.
AU - Sokolove, Jeremy
AU - Robinson, William H.
AU - Lingampalli, Nithya
AU - Nicholas, Anthony P.
AU - Talmon, Geoffrey A
AU - Su, Kaihong
AU - Zimmerman, Matthew C
AU - Klassen, Lynell Warren
AU - Thiele, Geoffrey Milton
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - anti-citrullinated protein antibody (ACPA)
KW - autoimmunity
KW - malondialdehyde–acetaldehyde adducts
KW - oxidative stress
KW - rheumatoid arthritis
KW - synovial fluid
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U2 - 10.1093/rheumatology/kex212
DO - 10.1093/rheumatology/kex212
M3 - Article
C2 - 28957552
AN - SCOPUS:85030759707
SN - 1462-0324
VL - 56
SP - 1794
EP - 1803
JO - Rheumatology (Oxford, England)
JF - Rheumatology (Oxford, England)
IS - 10
ER -