Cidin LL37 in pathogenesis of different human diseases has been investigated
Cidin LL37 in pathogenesis of different human diseases has been investigated by several research groups, mostly in the field of autoimmune and autoinflammatory diseases. Cathelicidin LL37 is overexpressed in inflamed skin in patients with psoriasis [7]. Human cathelicidin LL37 and its fragments inhibit HIV1 replication and the enzymes essential to the lifecycle of HIV, including HIV reverse transcriptase, HIV protease, and HIV integrase [8]. Plasma concentrations of cathelicidin LL37 are significantly higher in active hepatitis C virus infection and inactive hepatitis B virus infection, implicating cathelicidin LL37 in certain forms of hepatitis caused by hepatitis C virus and hepatitis B virus infections [9]. Human cathelicidins are involved in mucosal immunity of the respiratory tract, gastrointestinal tract, genitourinary tract, and eye [10]. HumanGasim Arthritis Research Therapy 2014, 16:105 2 ofcathelicidin is overexpressed in head and neck squamous cell carcinoma, and is strongly correlated with radiotherapy effectiveness [11]. Zhang and colleagues are the first to report elevated levels of cathelicidin LL37 in AAV, especially in patients with crescentic glomerulonephritis [1]. In this study, serum levels of cathelicidin LL37 and IFN correlated with crescent formation and also with serum creatinine. This observation is important because the correlation with cellular crescents would indicate a correlation with disease activity, which could be an important prognostic factor and may even suggest novel strategies for treatment if the association results from a pathogenic role for cathelicidin LL37. This hypothesis would be further substantiated if the correlation is with active cellular crescents accompanied by necrosis rather than with fibrotic crescents accompanied by glomerular scarring. The presence of crescents, especially cellular crescents, is an important histological marker of active glomerulonephritis, which can be ACY-241 web diagnosed only through renal biopsy, an expensive, time-consuming, and invasive technique. Cathelicidin LL37 is a serological marker, and is noninvasive and cost-effective compared with renal biopsy. Cathelicidin LL37 is stored as an inactive pro-form in secondary granules of neutrophils and is activated by PR3 (the autoantigen target of PR3-ANCA) when released at sites of inflammation [12]. Neutrophils and monocytes are activated by ANCA and release their lysosome and granule proteins, including MPO and PR3 [5,6]. Activated neutrophils also release cathelicidin LL37 [12,13]. Cathelicidin LL37 is found in neutrophil extracellular traps PubMed ID: PubMed ID: that are released by activated neutrophils [13]. These neutrophil extracellular traps have been implicated in the induction of autoimmunity and the mediation of inflammation in AAV [14]. To validate its value as a prognostic and predictive biomarker, future studies should investigate the levels of cathelicidin LL37 in patients with different severities of and different clinicopathologic phenotypes of AAV in large cohorts of patients with different levels of disease activity, remission, and relapse. More effective biomarkers are needed to improve prognostic and disease activity monitoring. Current clinical and laboratory observations that indicate a worse prognosis, especially for renal survival, are older age at diagnosis (>65 years), more severe renal failure (especially dialysis dependency), and PR3-ANCA versus MPO-ANCA [15-18]. Pa.