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Alessandro Iannaccone, TJ Hollingsworth, Natalia Lenchik, Sarka Beranova-Giorgianni, Ivan Gerling, Marko Z. Radic, Francesco Giorgianni; Association between macular phenotype and serum auto-antibodies (AAbs) against macular antigens in age-related macular degeneration (AMD): Preliminary studies. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5740.
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© ARVO (1962-2015); The Authors (2016-present)
We have documented that AMD sera exhibit circulating AAbs recognizing antigens expressed in the human macula [PLOS One 2015; 10: e0145323]. While these antigens [heat shock proteins HSPA8, HSPA9, and HSPB4, best known as alpha-crystallin A chain (CRYAA); Annexin A5 (ANXA5); Protein S100-A9; and the CD5-like (CD5L) protein/apoptosis inhibitor of macrophages (AIM)] are not “macula-specific”, they share a biologically plausible mechanistic connection to AMD via having key roles in autophagy, immunomodulation, and protection from oxidative stress and apoptosis. CD5L/AIM also has a role in oxidized (ox)LDL uptake, whereby it could also play a role in drusen biogenesis. Here we begin exploring possible correlates between macular phenotype and circulating AAbs recognizing these antigens in a discovery sample of AMD sera known to be positive for at least one of these autoreactivities to gauge their possible relevance to specific disease features.
Autoreactivities were measured by standard ELISA against corresponding purified or recombinant proteins as previously described [PLOS One 2015; 10: e0145323]. Macular AMD phenotype was investigated based on masked photo grading performed at baseline on all participants (n=18) by U. Wisconsin Reading Ctr. AREDS criteria. Characterized features included: maximum drusen size; drusen area; neovascular (nv)AMD; and presence and size of geographic atrophy (GA).
All AAb levels but anti-ANXA5 tended to be higher in bilateral advanced AMD (AREDS-4) than early/mid-stage AMD (AREDS-3) – especially anti-HSPA8, HSPA9 and S100A9. Anti-HSPA8 and anti-HSPA9 AAb levels were specifically higher in subjects with nvAMD but not with GA. Compared to the lowest quartile, the upper quartile of anti-HSPA8 and anti-CD5L/AIM AAb levels was associated with a 5- and 2-step higher bilateral drusen area, respectively.
These preliminary exploratory comparisons suggest that certain AMD features and disease stages may correlate with different autoreactivities, whereas others like anti-ANXA5 are elevated in AMD regardless of either feature. The association with greater drusen area for anti-CD5L/AIM AAbs is consistent with its emerging biological role in oxLDL uptake. The strong association with anti-HSPA8 with drusen area and nvAMD was not entirely expected and deserves further investigation.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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