Defective and excessive immunities in pediatric diseases.
Inflammatory and autoimmune diseases are classically considered as disorders arising from hyper-activation of immunity and hence are treated with drugs that suppress the lymphocyte activation and inflammation. Although this strategy has proven useful to cure symptoms, it rarely can heal the disease and long-term treatments are usually needed. Inflammatory and autoimmune diseases frequently occur also in patients with primary immune deficiency disease, proving that immune hyper-activation may paradoxically arise from defective function of immune genes. In these cases, the phenotype of hyper-activation is believed to reflect the attempts of the immune system to compensate for immune defects. Recent data suggest that similar mechanisms could be involved also in the pathogenesis of some multifactorial disorders, such as Crohn's disease and systemic lupus erythematosus. Based on these considerations, novel therapies could be developed to cure severe autoimmune and inflammatory disorders, not only by aiming to hyper-activation but as well by focusing on the possible underlying immune defects.
Division of Immunology, Children's Hospital Boston, Harvard Medical School, Karp 9, 09210, 1 Blackfan Circle, Boston, MA 02115, USA. luigi.notarangelo@childrens.harvard.edu
Luigi Daniele
LD
Notarangelo
Alberto
A
Tommasini
D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D002648:Child; D015195:Drug Design; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D012720:Severity of Illness Index