## 4 Discussion
In addition to this, the positive correlation between IL-17A with PD and CAL in gingival tissue agrees with that reported by another study group [28]; the higher the IL-17A concentration, the greater the probing depth, and insertion loss. Therefore, IL-17A and IL-17 RA positively correlate in the gingival tissue and appear to be crucial to the loss of insertion and alveolar resorption. This could be because when IL-17A binds to IL-17 RA it triggers the expression of chemokines, pro-inflammatory cytokines, and metalloproteinases (MMPs), promoting a crucial pro-inflammatory environment for osteoclastogenesis and bone erosion in periodontitis [56]. When correlating the levels of IL-17A between the plasma samples and gingival tissues, an inverse behavior was observed. While in plasma, there is a decrease in IL-17A levels, in gingival tissue the levels of this cytokine increase. This is probably because plasma can only detect IL-17A released by cells. In contrast, in gingival tissue, it can determine whether IL-17A is bound to the receptor on the cell membrane or intracellularly. Similarly, this is probably because that IL-17A in plasma is blocked by the SIL-17 RA, as other authors have proposed [12]. This could explain the discrepancy of IL-17A levels in different biological fluids. Furthermore to these findings, a positive correlation was found between IL-23 and IL-17A in the gingival tissue that coincides with the path of the IL-23/IL-17 axis since the production of IL-17A depends on the stimulus of IL-23 [6]. This study has some limitations, principally the effect size and power of IL-23R in plasma and IL-23 in gingival tissue that was inadequate to evaluate the complete behavior of the IL-23/IL-17 axis. Another limitation was the sample size; it is important to evaluate these molecules in more patients with periodontitis to have better study groups classified by the periodontal grades and stages, this can help to determine if there is a significant difference in the severity and progression of periodontal disease. In the future, the IL-23/IL-17A axis and their receptors in the gingival tissue of periodontitis patients will be analyzed by Western blot and mass spectrometry, which will allow us to study the functionality of the isoforms from the IL-23/IL-17 axis and their association with periodontitis progression in detail. In this sense, different biological drugs (monoclonal antibodies) have been used in different pathologies such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis to counteract the proinflammatory effect of various cytokines and receptors, including IL-17, IL-23, and IL-17 RA, and extensive improvements have been observed in the clinical and histological features of these diseases [57, 58, 59, 60]. For example, broadlumab, approved for the treatment of psoriasis, which consists of an IgG2a monoclonal antibody that specifically binds to IL-17 RA and blocks the signaling of various IL-17 isoforms (IL-17A and IL-17F) [61, 62]. It would be interesting to carry out the corresponding experimental phases to test this kind of broadlumab, because in this study, we found elevated IL-17 RA in the gingival tissue of patients with periodontitis. In this way, it may be possible to reduce RANKL production by fibroblasts [9], and thus block bone resorption generated by the IL-17/IL-17 RA and RANK/RANKL systems in patients with periodontitis.