Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression

Iannaccone, Alessandro; Neeli, Indira; Krishnamurthy, P.; Lenchik, Nataliya; Wan, Haibao; Gerling, Ivan; Desiderio, Dominic M.; Radic, Marko

doi:10.1007/978-1-4614-0631-0_2

Cited by 14 publications

(11 citation statements)

References 23 publications

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“…This strengthens the notion that AMD greatly overlaps with or possibly is an autoimmune-related disease. It remains to be seen whether these patients at risk for AMD might profit from anti-inflammatory or immuno-suppressive medication [93–95]. …”

Section: Discussionmentioning

confidence: 99%

Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

et al. 2017

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BackgroundAge-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits.MethodsFor each of 60 complex diseases/traits with publicly available genome-wide significant association data, the lead genetic variant per independent locus was extracted and a genetic score was calculated for each disease/trait as the weighted sum of risk alleles. The association with AMD was estimated based on 16,144 AMD cases and 17,832 controls using logistic regression.ResultsOf the respective disease/trait variance, the 60 genetic scores explained on average 4.8% (0.27–20.69%) and 16 of them were found to be significantly associated with AMD (Q-values < 0.01, p values from < 1.0 × 10–16 to 1.9 × 10–3). Notably, an increased risk for AMD was associated with reduced risk for cardiovascular diseases, increased risk for autoimmune diseases, higher HDL and lower LDL levels in serum, lower bone-mineral density as well as an increased risk for skin cancer. By restricting the analysis to 1824 variants initially used to compute the 60 genetic scores, we identified 28 novel AMD risk variants (Q-values < 0.01, p values from 1.1 × 10–7 to 3.0 × 10–4), known to be involved in cardiovascular disorders, lipid metabolism, autoimmune diseases, anthropomorphic traits, ocular disorders, and neurological diseases. The latter variants represent 20 novel AMD-associated, pleiotropic loci. Genes in the novel loci reinforce previous findings strongly implicating the complement system in AMD pathogenesis.ConclusionsWe demonstrate a substantial overlap of the genetics of several complex diseases/traits with AMD and provide statistically significant evidence for an additional 20 loci associated with AMD. This highlights the possibility that so far unrelated pathologies may have disease pathways in common.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0418-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

et al. 2017

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“…Serum autoantibodies may also be useful biomarkers that play a mechanistic role in AMD (Adamus et al, 2014; Donoso et al, 2006; Iannaccone et al, 2012; Nussenblatt and Ferris, 2007; Penfold et al, 2001). Iannaccone et al (2015) identified autoantibodies in AMD sera, even in early-stage disease, including Annexin A5 (ANXA5), Protein S100-A9 (also known as calgranulin B that, when complexed with S100A8, forms calprotectin), and heat shock proteins, HSPA8, HSPA9, and HSPB4 (also known as alpha-crystallin A chain), which may play a role in AMD via autophagy compromise and downstream activation of the inflammasome (Iannaccone et al, 2012). …”

Section: Biomarkers Of Disease and Progressionmentioning

confidence: 99%

Risk factors and biomarkers of age-related macular degeneration

Lambert

Elshelmani

Singh

et al. 2016

Progress in Retinal and Eye Research

282

240

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A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings.

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“…CFH is transcriptionally upregulated by STAT1, but oxidative stress, one of the most important risk factors for AMD, can disrupt this process by acetylating FOXO3, which competes with STAT1 for binding to the CFH promoter [15,52]. It is also known that STAT1-deficient mouse are highly susceptible to autoimmune disorders [53] and given that AMD may be considered an autoimmune disease [54,55], preserving STAT1 activation by IFN-γ may be important in mitigating AMD progression. Furthermore, IFN-γ can tilt the balance toward STAT1 by deactivating STAT3.…”

Section: Is There Any Beneficial Role Of Ifn-γ In Terms Of Protectivementioning

confidence: 99%

Immuno-modulatory Effect of IFN-gamma in AMD and its Role as a Possible Target for Therapy

Jiang¹,

Cao²

2012

J Clin Exp Ophthalmol

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Age-related macular degeneration (AMD) is a neurodegenerative disease characterized by retinal cell atrophy, and/or choroidal neovascularization in the macula and constitutes the most common cause of blindness among the elderly in industrialized countries. The management of AMD is constrained by our insufficient knowledge of its underlying mechanisms. Recent studies point towards an emerging involvement of interferon-gamma (IFN-γ), a soluble cytokine associated with innate and adaptive immunity. IFN-γ promotes proinflammatory responses by activating proinflammatory cytokines and chemokines, thereby recruiting immune cells such as macrophages and T cells. On the other hand, IFN-γ modulates inflammatory response by upregulating antiinflammatory factors or inhibiting development of immune cells related to autoimmune response. The complex role of IFN-γ in AMD pathogenesis is intriguing and worth further investigation in terms of therapeutic development.

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Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression

Cited by 14 publications

References 23 publications

Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

Risk factors and biomarkers of age-related macular degeneration

Immuno-modulatory Effect of IFN-gamma in AMD and its Role as a Possible Target for Therapy

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