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. 2023 Aug 1;12(8):1.
doi: 10.1167/tvst.12.8.1.

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy

Vivian Rajeswaren  1 , Brandie D Wagner  1   2 , Jennifer L Patnaik  1 , Naresh Mandava  1 , Marc T Mathias  1 , Niranjan Manoharan  1 , Talisa E De Carlo Forest  1 , Ramya Gnanaraj  1 , Anne M Lynch  1 , Alan G Palestine  1 ; University of Colorado Retina Research Group
Affiliations

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy

Vivian Rajeswaren et al. Transl Vis Sci Technol. .

Abstract

Purpose: Chronic local inflammation underlies the pathogenesis of age-related macular degeneration (AMD) causing damage to the neurosensory retina. However, there is minimal research on systemic cell-mediated inflammation in AMD. Interleukin-4 (IL-4) is an immunoregulatory cytokine with an important role in modulating inflammation in chronic immune mediated disease. The purpose of this study was to: (1) investigate the role of systemic IL-4 in patients with intermediate AMD (iAMD) and in geographic atrophy (GA), an advanced form of AMD, compared to controls without AMD, and (2) determine if IL-4 levels are moderated by sex.

Methods: We examined plasma levels of IL-4 in patients with iAMD, GA, and controls without AMD included in the University of Colorado AMD registry (August 2014 to June 2021). Cases and controls were defined by multimodal imaging. IL-4 was measured by multiplex immunoassay. Data were analyzed using a nonparametric rank based linear regression model fit to IL-4.

Results: There were 199 patients with iAMD, 97 patients with GA, and 139 controls, with a percentage of female patients 61%, 55%, and 66%, respectively. We demonstrated significantly higher median IL-4 levels in GA (35.3; interquartile range [IQR] = 22.8-50.5) compared to iAMD (6.1; IQR = 2.2-11.3, P < 0.01) and controls (10.7; IQR = 5.0-16.8, P < 0.01). There were no significant differences in levels of IL-4 for cases and controls when stratified by sex.

Conclusions: These findings demonstrate a systemic immunological difference between iAMD and GA, indicating IL-4 may be a systemic biomarker for GA development.

Translational relevance: The plasma biomarker IL-4 is significantly elevated in patients with GA.

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Conflict of interest statement

Disclosure: V. Rajeswaren, None; B.D. Wagner, None; J.L. Patnaik, None; N. Mandava, None; M.T. Mathias, None; N. Manoharan, None; T.E. De Carlo Forest, None; R. Gnanaraj, None; A.M. Lynch, None; A.G. Palestine, None

Figures

Figure.
Figure.
Plasma levels of IL-4 with a sex by AMD group interaction. Boxplot showing IL-4 levels for iAMD, GA, and control patients and IL-4 levels across groups when stratified by sex. The box extends to the 25th and 75th percentiles, the line represents the median value. Individual colored circles/plus signs illustrate raw values. Female patients are represented as blue circles and male patients are represented as red plus signs.
See this image and copyright information in PMC

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