Abstract
Purpose :
People with AIDS have an increased prevalence and incidence of age-related macular degeneration (AMD) v HIV-uninfected persons. Previous work demonstrated that elevated plasma levels of the biomarkers C-reactive protein (CRP) and soluble CD14 (sCD14) were associated with an increased risk of incident AMD, and that elevated plasma levels of interleukin (IL)-6, CXC chemokine ligand 10 (CXCL10), sCD14, and sCD163 were associated with a decreased risk of cataract in people with AIDS. Relationships between AMD and cataract with plasma levels of the follwoing biomarkers were evaluated: soluble TNF receptor 2 (sTNFR2), IL-18, and the chemokine ligands CCL2, CCL4, and CX3CL1.
Methods :
Crypreserved baseline plasma specimens from the Longitudinal Study of the Ocular Complications of AIDS were assayed for plasma biomarkers in 2 study sub-populations: 1) a case control study of participants with incident AMD and age, sex, and race/ethnicity matched controls without AMD; 2) a sub-cohort of participants followed for incident cataract.
Results :
After adjusting for plasma HIV RNA level, CD4+ T cell count, and smoking, elevated baseline plasma levels of soluble TNF receptor 2 (sTNFR2) and IL-18 (mean differences[cases-controls] 0.11 log10 (pg/mL); 95% CI 0.01, 0.20; P=0.024 and 0.13 log10 (pg/mL); 95% CI 0.01, 0.24; P=0.037, respectively) were associated with incident AMD. Using a competing risk (for mortailty) analysis, elevated baseline standardized log10 plasma levels of the following biomarkers (adjusted sub-distribution hazard ratios [95% CI]) were associated with a decreased risk of cataract: CC chemokine ligand 2 (CCL2) (0.73 [0.62, 0.86] P<0.001), sTNFR2 (0.76 [0.64, 0.90] P=0.002), IL-18 (0.75 [0.64, 0.88] P<0.001); and CX3CL1 (0.78 [0.67, 0.92] P=0.002. , CCL2, CCL4, IL-18, sTNFR2, CX3CL1,each were associated with an increased risk of mortality.
Conclusions :
Elevated plasma levels of biomarkers associated with monocyte activation (sCD14) and with NLRP-3 inflammasome activation (IL-18, sTNFR2, CRP) are associated with incident AMD in persons with AIDS, whereas elevated plasma levels of multiple biomarkers of systemic inflammation are associated with a decreased risk of cataract. These data suggest that specific systemic inflammatory pathways contribute to the pathogenesis of AMD in this population.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.