Mikuls Ted R, Duryee Michael J, Rahman Rafid, Anderson Daniel R, Sayles Harlan R, Hollins Andrew, Michaud Kaleb, Wolfe Frederick, Thiele Geoffrey E, Sokolove Jeremy, Robinson William H, Lingampalli Nithya, Nicholas Anthony P, Talmon Geoffrey A, Su Kaihong, Zimmerman Matthew C, Klassen Lynell W, Thiele Geoffrey M
Veteran Affairs Nebraska-Western Iowa Health Care System.
Department of Internal Medicine, Division of Cardiovascular Medicine.
Rheumatology (Oxford). 2017 Oct 1;56(10):1794-1803. doi: 10.1093/rheumatology/kex212.
To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA.
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.
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).
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.
描述类风湿关节炎（RA）患者关节组织和血清中丙二醛 - 乙醛（MAA）加合物及抗MAA抗体的表达情况。
检测了29例RA患者和13例骨关节炎（OA）患者的配对血清和滑膜液（SF）。对抗MAA抗体、类风湿因子（RF）、抗环瓜氨酸肽抗体（ACPA）和总免疫球蛋白进行定量分析。比较了疾病组内和组间的SF - 血清检测指标。采用免疫组织化学方法检测RA和OA滑膜组织中MAA、瓜氨酸和特定白细胞抗原的存在及共定位情况。
RA患者循环血和SF中的抗MAA抗体浓度比OA患者高1.5至5倍。配对的RA患者SF中IgG（P < 0.001）、IgM（P = 0.006）和IgA（P = 0.036）抗MAA抗体高于血清，而总免疫球蛋白、RF或ACPA未观察到这种差异。在RA滑膜组织中，证实了MAA与瓜氨酸以及CD19 +或CD27 + B细胞的共定位，其程度远高于MAA或瓜氨酸与T细胞、单核细胞、巨噬细胞或树突状细胞的共定位（P < 0.01）。
与血清相比，RA关节中抗MAA抗体浓度更高，这一发现对于其他疾病相关自身抗体未观察到。MAA和瓜氨酸与成熟B细胞的共定位，以及抗MAA免疫反应的局部富集，提示MAA加合物形成参与了局部自身抗体的产生。
