Immune response against HtrA proteases in children with cutaneous mastocytosis
AbstractMast cells play important role in both innate and adaptive immunity but clonal proliferation of abnormal mast cells in various organs leads to mastocytosis. The skin variant of the disease, cutaneous mastocytosis (CM) is the most frequent form of mastocytosis in children. The HtrA proteases are modulators of important cellular processes, including cell signaling and apoptosis, and are connected with development of many pathologies. The above and the observation that mast cells constitutively release the HtrA1 protein, prompted us to investigate a possible involvement of the HtrA proteins in pediatric CM.We assayed the levels of the serum autoantibodies (IgG) against the recombinant HtrA proteins (HtrA1-4) in children with CM (n= 36) and in healthy controls (n= 62). The anti-HtrA IgGs were detected using enzyme linked immunosorbent assay (ELISA) and Western-blotting. In the CM sera the levels of the anti-HtrA1 and anti-HtrA3 autoantibodies were significantly increased compared to the control group while the HtrA proteins’ levels were comparable. No significant differences in the anti-HtrA2 IgG level were found, and the anti-HtrA4 IgGs had a tendency to decrease. In healthy children, the IgG levels against the HtrA1, -3 and -4 increased significantly with the age of children; no significant changes were observed for the anti-HtrA2 IgG. Our results suggest involvement of the HtrA1 and HtrA3 proteins in pediatric CM; the involvement of the HtrA4 protein is possible but needs to be investigated further. In healthy children, the autoantibody levels against HtrA1, -3 and -4 but not against HtrA2 increase with age.
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