Circulating IgM Antibody Levels Against Oxidation-Specific Epitopes and Their Association With Age-Related Macular Degeneration

BACKGROUND: Cardiovascular disease (CVD) is associated with age-related macular degeneration (AMD), suggesting shared pathogenic pathways. Natural IgM antibodies targeting oxidation-specific epitopes (OSEs) are well characterized in CVD and may contribute to AMD. To date, no observational study has assessed the association between OSE-IgM and AMD, including among individuals with concomitant CVD. Here, we investigate this relationship in large population-based cross-sectional data of old-aged individuals. METHODS: We measured IgM antibodies against phosphocholine-modified BSA (PC), MDA-LDL (malondialdehyde-modified low-density lipoprotein), and CuOx-LDL (copper-oxidized LDL) in up to 2264 participants with and without AMD of the AugUR study (Age-Related Diseases: Understanding Genetic and Nongenetic Influences—a Study at the University of Regensburg; 627 cases, 1637 controls; age, 70–95 years). Antibody levels were inverse-normalized, and multinomial mixed regression analyses were performed to evaluate their associations with different AMD stages. RESULTS: Women exhibited significantly higher levels of all 3 OSE-IgM compared with men. Elevated levels of IgM against PC were associated with 12% decreased odds (odds ratio, 0.88 [95% CI, 0.80–0.97]; P =0.01) for any AMD. When we investigated OSE-IgM associations with different stages of AMD (early AMD, late AMD), we found that all 3 OSE-IgM were associated with ≈20% lower odds for late AMD, but none with early AMD. Associations of OSE-IgM with late AMD were stronger in men than in women. Of the participants, 490 individuals had documented CVD. A significant interaction was observed between levels of PC IgM and CVD status in their associations with early AMD ( P =0.049). In a subset of participants with CVD, PC IgM levels were associated with 34% decreased odds (odds ratio, 0.66 [95% CI, 0.51–0.86]; P =0.002) for early AMD. CONCLUSIONS: This study identifies an inverse association between IgM antibodies targeting PC, MDA-LDL, and CuOx-LDL and late AMD, but not with early AMD. However, in the early stage of AMD, an association with PC IgM is only observed when the participants had documented CVD. These findings may suggest a possible protective role of OSE-IgM antibodies in AMD pathogenesis and progression.