Abstract
Human cathelicidin LL37 is a cationic antimicrobial peptide active against bacteria and viruses and exerting immune modulatory functions. LL37 can be also a target of autoreactive B- and T-lymphocytes in autoimmune settings. Irreversible post-translational modifications, such as citrullination and carbamylation, mainly occurring at the level of cationic amino acids arginine and lysine, can affect the inflammatory properties and reduce antibacterial effects. Moreover, these modifications could be implicated in the rupture of immune tolerance to LL37 in chronic conditions such as psoriatic disease and cutaneous lupus (LE)/systemic lupus erythematosus (SLE). Here, we describe the generation and fine specificity of six recombinant antibodies (MRB137–MRB142), produced as a monovalent mouse antibody with the antigen-binding scFv portion fused to a mouse IgG2a Fc, and their ability to recognize either native or citrullinated LL37 (cit-LL37) and not cross-react to carbamylated LL37. By using these antibodies, we detected native LL37 or cit-LL37 in SLE and rheumatoid arthritis (RA) sera, and in LE skin, by ELISA and immunohistochemistry, respectively. Such antibodies represent previously unavailable and useful tools to address relationships between the presence of post-translational modified LL37 and the immune system status (in terms of innate/adaptive responses activation) and the clinical characteristics of patients affected by chronic immune-mediated diseases or infectious diseases.
Highlights
Human cathelicidin is an antimicrobial peptide (AMP), called CAP18 and FALL39, and is the product of the human gene CAMP
We could not find any relationship between the detection of cit-LL37 and native LL37 in rheumatoid arthritis (RA) sera and disease parameters such as ESR and CRP (C-reactive protein), in RA patients. These results suggest that the two monoclonal antibodies MRB139 and MRB142 can discriminate between presence of native LL37 and cit-LL37 in sera, respectively, larger clinical studies are needed to confirm the importance of detection of native LL37/cit-LL37 in circulation in chronic diseases such as RA and systemic lupus erythematosus (SLE)
We report the successful generation of new monoclonal antibodies that are able to recognize either native LL37 or cit-LL37
Summary
Human cathelicidin is an antimicrobial peptide (AMP), called CAP18 and FALL39, and is the product of the human gene CAMP. It has been shown that LL37 is modified in vitro by citrullination and carbamylation, two types of irreversible post-translational modifications (PTMs), in which cationic amino acids are substituted by citrullines or homocitrullines, respectively [21,22]. These and other studies addressed the effect of such substitutions in vitro, showing impairment of some functions such as reduction of the antimicrobial activity, as well as gain of functions, such as increase of the immune-cell recruitment activity (chemotaxis) [21,22,23,24]. Citrullination and carbamylation can be mediated by activation of protein arginine deiminases (PADs) and myeloperoxidase (MPO), respectively, both products of neutrophils among other cells, and both PTMs can be especially ascribed to neutrophil activity [25,26,27,28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
