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. 2025 May 12:16:1601145.
doi: 10.3389/fimmu.2025.1601145. eCollection 2025.

C-reactive protein conformations and their association with the IL-1β/IL-6 pathway in ocular inflammatory conditions

Mercedes S Nabaes Jodar  1 , Víctor Llorenç  1   2 , Marc Figueras-Roca  1   2 , Maite Sainz de-la-Maza  1   2 , Alfredo Adán  1   2 , Blanca Molins  1
Affiliations

C-reactive protein conformations and their association with the IL-1β/IL-6 pathway in ocular inflammatory conditions

Mercedes S Nabaes Jodar et al. Front Immunol. .

Abstract

Introduction: C-reactive protein (CRP) plays a critical role in the innate immune system and serves as a biomarker for various inflammatory conditions. CRP is a dynamic protein undergoing conformational changes between pentameric (pCRP) and monomeric (mCRP) conformations. pCRP is the well-established systemic marker of inflammation, while mCRP is associated with localized tissue inflammation.

Methods: This study aimed to evaluate systemic levels of pCRP, mCRP, interleukin-6 (IL-6), and interleukin-1β (IL-1β) in patients with a variety of intraocular inflammatory conditions, including diabetic macular edema (DME) and non-infectious uveitis such as Behçet's disease (BD), Birdshot retinochoroidopathy (BSRC), HLA-B27-associated uveitis, and undifferentiated uveitis (UU).

Results: A total of 77 subjects were included. mCRP levels were significantly elevated in BD, DME, and UU compared to controls (p = 0.014, p = 0.036, and p = 0.031, respectively). The mCRP/pCRP ratio was also significantly higher in DME and UU (p = 0.035 and p = 0.011, respectively). In addition, a strong positive correlation was observed between IL-6 and IL-1β (ρ = 0.638, p <0.0001). No significant differences in serum levels of pCRP, IL-6, or IL-1β were observed among the groups.

Conclusions: These findings suggest that mCRP, rather than pCRP, may be a more specific systemic biomarker for certain intraocular inflammatory conditions. The involvement of the CRP axis and the strong correlation between IL-6 and IL-1β underscore the interaction of these key inflammatory mediators, providing further insight into the targeting of CRP axis for therapeutic purposes.

Keywords: C-reactive protein (CRP); diabetic macular edema; interleukin-1β (IL-1β); interleukin-6 (IL-6); ocular inflammation; uveitis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Systemic levels of CRP-axis in intraocular inflammatory conditions: (A) pCRP levels, (B) mCRP levels, (C) mCRP/pCRP ratio, (D) mCRP detection rate (%), (E) IL-6 levels, and (F) IL-1β. levels in intraocular inflammatory conditions and control group. *P<0.05 vs. control.
See this image and copyright information in PMC

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