Use of Genetic Profiling in Leprosy to Discriminate Clinical Forms of the Disease

Abstract

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

Association of LILRA2 (ILT1, LIR7) splice site polymorphism with systemic lupus erythematosus and microscopic polyangiitis

“…15 A number of recent observations demonstrate the crucial role of type I interferon in SLE. 28 Because TLR signals are important inducers of type I interferons, association with SLE could be explained if D419-421 isoform may promote stronger TLR signals.…”

“…15 As Th1 cytokines have been implicated both in SLE and MPA, 29,30 Th1/Th2 imbalance caused by D419-421 isoform could be another potential mechanism of association. The association of LILRA2 was in a recessive manner, which was responsible for the deviation of this genotype from the HardyWeinberg equilibrium in SLE.…”

“…13,14 It is reported that the expression of LILRA2 was significantly upregulated in lesions of lepromatous leprosy patients. 15 The synovium from patients with rheumatoid arthritis (RA) showed extensive expression of inhibitory LILRB2 and activating LILRA2 on macrophages and neutrophils. 16 Although some of the LILRs and KIRs bind to HLA class I molecules or UL-18, a HLA class I homolog expressed by human cytomegalovirus, 17,18 ligands for LILRA2 have not been identified.…”

“…21 On the other hand, it is reported that activation of LILRA2 suppresses innate host defense mechanisms by shifting monocyte production from IL-12 toward IL-10 and blocking toll-like receptor (TLR)-mediated antimicrobial activity. 15 In mice, PIR-A, an ortholog of LILRA2, has been shown to be an essential costimulatory receptor for osteoclast differentiation. 22 RA is a chronic rheumatic disease that leads to progressive joint destruction.…”

La polarisation des macrophages, le noeud gordien des infections bactériennes ?

“…Les macrophages M2 sont également associés aux infections mycobactériennes chroniques : c'est ainsi que des macrophages M2 sont présents dans les lésions ulcéreuses précoces de la maladie de Buruli [24,34]. Dans les lésions lépromateuses, les macrophages produisent en excès de l'IL-10 [3] et LIR-7, un membre de la famille des leukocyte Ig-like receptors dont on a montré par ailleurs qu'il inhibe les réponses immunes innées en favorisant la production d'IL-10 par les monocytes et en déprimant leur potentiel microbicide [25]. Il est cependant probable que la lèpre lépromateuse, considérée comme paradigmatique des réponses Th2, n'est pas associée à un pur profil M2 des macrophages puisque des marqueurs M1 avérés ou probables sont également exprimés dans les lésions lépromateuses [3].…”