Objective
As a product of oxidative stress associated with tolerance loss in other disease states, we investigated the presence of malondialdehyde-acetaldehyde (MAA) adducts and circulating anti-MAA antibody in rheumatoid arthritis (RA).
Methods
Synovial tissues from RA and osteoarthritis patients were examined for the presence of MAA-modified and citrullinated proteins. Anti-MAA antibody isotypes were measured in RA cases (n = 1720) and healthy controls (n = 80) by ELISA. Antigen-specific anti-citrullinated protein antibody (ACPA) was measured in RA cases using a multiplex antigen array. Anti-MAA isotype concentrations were compared in a subset of cases (n = 80) and matched controls (n = 80). Associations of anti-MAA antibody isotypes with disease characteristics, including ACPA, were examined in all RA cases.
Results
MAA adducts were increased in RA synovial tissues relative to osteoarthritis and co-localized with citrullinated protein. Anti-MAA antibody isotypes were increased in RA cases vs. controls (p < 0.001). Among RA cases, anti-MAA antibody isotypes were associated with ACPA and RF positivity (p < 0.001) in addition to select measures of disease activity. Higher anti-MAA antibody concentrations were associated with a higher number of positive antigen-specific ACPA analytes in high titer (p < 0.001) and a higher ACPA score (p < 0.001) independent of other covariates.
Conclusion
MAA adduct formation is increased in RA and appears to result in robust antibody responses that are strongly associated with ACPA. These results support speculation that MAA formation may be a co-factor that drives tolerance loss resulting in the autoimmune responses characteristic of RA.
| THE IMPERATIVESIn recent years, health systems across the United States and around the world have faced persistent challenges including the underutilization of necessary care, the overutilization of inappropriate care, rising costs, disparities in access to care, patient safety concerns, System-level improvement requires a broad and diverse intellectual community. The necessary transdisciplinary community will be composed of scholars with expertise in social, political, technical, and clinical fields, along with many others who bring critical experience from practice. It follows that a third imperative is to form this community and provide it with a gathering place for its evolving scientific ideas and insights.
This nested case-control study uses data from the Mayo Clinic Spontaneous Coronary Artery Dissection Registry to investigate the association of pregnancy with spontaneous coronary artery dissection recurrence among women with a history of coronary artery dissection.
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