Anti-IL17A Monoclonal antibody, clone 28C8 [PE]

Background: Rheumatoid Arthritis (RA) is an autoimmune systemic disease and in its pathogenesis participate several proinflammatory cytokines, including those produced by Th17 cells. We performed a systematic review aiming to assess the associations between polymorphisms in Th17 cytokines, namely IL-17A, IL-17F, IL-21 and IL-22, and susceptibility to RA. Methods: We searched three electronic databases (MEDLINE, Scopus and Web of Science) for observational studies assessing the association between susceptibility to RA (or its clinical presentation) and polymorphisms of the cytokines IL-17A, IL-17F, IL-21 and IL-22. From the selected studies, we extracted information on the studied polymorphisms, assessed outcomes, and demographic characteristics of participants. We performed random effects meta-analyses assessing the associations between susceptibility to RA and different genotypes of the IL17A rs2275913, IL-17F rs763780 and IL-17F rs2397084 polymorphisms. Primary studies' quality was assessed using the Q-Genie tool. Results: Fifteen studies were included in this systematic review. Five IL-17A polymorphisms were reported to be associated with susceptibility to RA. For the IL-17A rs2275913 polymorphism, our meta-analysis showed the AA genotype to be significantly associated with lower susceptibility to RA (OR = 0.76; 95%CI = 0.61-0.93; p = 0.01), while the opposite was observed for the GG genotype (OR = 1.20; 95%CI = 1.06-1.35; p = 0.01). Concerning IL-17F rs763780 polymorphism, the TT genotype was found to be significantly less frequent in RA patients (OR = 0.49; 95%CI = 0.31-0.77; p = 0.002), while the opposite was observed for the CT genotype (OR = 2.00; 95%CI = 1.03-3.87; p = 0.04). No significant associations were found regarding rs2397084 polymorphisms. For IL-21, rs6822844 and rs4505848 were described to have significant associations with susceptibility to RA. No studies were found assessing IL-22 polymorphisms in RA. Conclusions: IL-17A rs2275913 and IL-17F rs763780 polymorphisms are significantly associated with susceptibility to RA and with different clinical characteristics of this disease.

Obesity is a risk factor for the development of asthma. Obese mice exhibit innate airway hyperresponsiveness (AHR), a characteristic feature of asthma, and IL-17A is required for development of AHR in obese mice. The purpose of this study was to examine the temporal association between the onset of AHR and changes in IL-17A during the development of obesity by high-fat feeding in mice. At weaning, C57BL/6J mice were placed either on mouse chow or on a high-fat diet (HFD) and examined 9, 12, 15, 18, or 24 weeks later. Airway responsiveness to aerosolized methacholine (assessed via the forced oscillation technique) was greater in mice fed HFD versus chow for 24 weeks but not at earlier time points. Bronchoalveolar lavage and serum IL-17A were not affected by either the type or duration of diet, but increased pulmonary IL 17a mRNA abundance was observed in HFD versus chow fed mice after both 18 and 24 weeks. Flow cytometry also confirmed an increase in IL-17A(+) gamma delta T cells and IL-17A(+) CD4(+) T (Th17) cells in lungs of HFD versus chow fed mice. Pulmonary expression of Cfd (complement factor D, adipsin), a gene whose expression can be reduced by IL-17A, decreased after both 18 and 24 weeks in HFD versus chow fed mice. Furthermore, pulmonary Cfd mRNA abundance correlated with elevations in pulmonary Il17a mRNA expression and with AHR. Serum levels of TNF alpha, MIP-1 alpha and MIP-1 beta, and classical markers of systemic inflammation of obesity were significantly greater in HFD than chow fed mice after 24 weeks, but not earlier. In conclusion, our data indicate that pulmonary rather than systemic IL-17A is important for obesity-related AHR and suggest that changes in pulmonary Cfd expression contribute to these effects of IL-17A. Further, the observation that increases in Il17a preceded the development of AHR by several weeks suggests that IL-17A interacts with other factors to promote AHR. The observation that the onset of the systemic inflammation of obesity coincided temporally with the development of AHR suggest that systemic inflammation may be one of these factors.