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Selection and evaluation of single domain antibody against p19 subunit of IL-23 by phage display for potential use as an autoinflammatory therapeutic

Abdo AIK, Nordin F, Tye GJ

Int Immunopharmacol, 2024 Aug 20;137:112371.
PMID: 38852516 DOI: 10.1016/j.intimp.2024.112371

IL-23 is a double-subunit cytokine that plays an important role in shaping the immune response. IL-23 was found to be associated with several autoinflammatory diseases by generating sustained inflammatory loops that lead to tissue damage. Antibody neutralization of IL-23 was proven to be effective in ameliorating associated diseases. However, antibodies as large proteins have limited tissue penetration and tend to elicit anti-drug antibodies. Additionally, anti-IL-23 antibodies target only one subunit of IL-23 leaving the other one unneutralized. Here, we attempted to isolate a recycling single domain antibody by phage display. One of IL-23 subunits, p19, was expressed in E. coli fused to Gamillus protein to stabilize the α-helix-only p19. To remove Gamillus binders, two biopanning methods were investigated, first, preselection with Gamillus and second, challenge with IL-23 then on the subsequent round challenge with p19-Gam. The isolation of calcium-dependent and pH-dependent recycling binders was performed with EDTA and citrate buffers respectively. Both methods of panning failed to isolate high-affinity and specific p19 recycling binders, while from the second panning method, a high affinity and specific p19 standard binder, namely H11, was successfully isolated. H11 significantly inhibited the gene expression of IL-17 and IL-22 in IL-23-challenged PBMCs indicating H11 specificity and neutralizing ability for IL-23. The new binder due to its small size can overcome antibodies limitations, also, it can be further engineered in the future for antigen clearance such as fusing it to cell penetrating peptides, granting H11 the ability to clear excess IL-23 and enhancing its potential therapeutic effect.

Matched MeSH terms: Interleukin-23/metabolism
Tissue Interleukin-17 and Interleukin-23 as Biomarkers for Orbital Granulomatosis with Polyangiitis

Isa H, Luthert P, Rose G, Verity D, Pusey C, Tomkins-Netzer O, et al.

Ophthalmology, 2015 Oct;122(10):2140-2.
PMID: 26116342 DOI: 10.1016/j.ophtha.2015.04.016
Matched MeSH terms: Interleukin-23/metabolism*
Evaluation of Interleukin-17 and Interleukin-23 in Pterygium: Immunohistochemistry Study

Tiong KI, Mohd Zahidin AZ, Sumugam SKA, Uchang J, Mohd Isa HD

Asia Pac J Ophthalmol (Phila), 2017;6(5):403-406.
PMID: 28868833 DOI: 10.22608/APO.2017134

PURPOSE: To compare the interleukin-17 (IL-17) and interleukin-23 (IL-23) positive cell counts between pterygium and normal conjunctiva.
DESIGN: A case-control study.
METHODS: This study received ethical approval (NMRR Research ID 23957) and informed consent was obtained from all participants. It involved 20 participants with 20 samples of pterygium and 20 samples of normal conjunctiva that were obtained from the same eye of each participant. All the participants underwent history taking, slit lamp examination, and pterygium excision surgery. Both samples underwent immunohistochemistry procedure. Pretreatment procedure was conducted using heat-induced epitope retrieval with PT link, subsequently followed by EnVision FLEX staining procedure and incubation with anti‒IL-17 antibody and anti‒IL-23 antibody. Slides were examined in high-power fields (400x) for both samples in 3 different fields. Total positive stained cell counts in all 3 fields with IL-17 and IL-23 between pterygium and normal conjunctiva were analyzed by using Wilcoxon signed rank test.
RESULTS: IL-17 positive cell counts for normal conjunctiva showed mean 196.10 ± 80.487 but for pterygium was 331.10 ± 108.416. As for IL-23, the mean for positive cell counts for normal conjunctiva was 62.10 ± 33.462 and IL-23 positive cell counts for pterygium showed mean 102.95 ± 41.378. Both IL-17 and IL-23 were significantly increased in pterygium compared with normal conjunctiva (P < 0.001).
CONCLUSIONS: Both IL-17 and IL-23 were found to be significantly higher in the pterygium group than in the normal conjunctiva group with P < 0.001 by Wilcoxon signed rank test.

Matched MeSH terms: Interleukin-23/metabolism*
Fulltext Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice

Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY

Drug Des Devel Ther, 2015;9:3923-34.
PMID: 26251571 DOI: 10.2147/DDDT.S86345

Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA.

Matched MeSH terms: Interleukin-23/metabolism