Plasma chitotriosidase and CCL18: Early biochemical surrogate markers in type B Niemann‐Pick disease

Abstract

Type B Niemann-Pick disease (NPD) is a nonneuronopathic lysosomal storage disorder which is characterized by accumulation of sphingomyelin-laden macrophages. The availability of plasma markers for storage cells may be of great value in facilitating therapeutic decisions. Given the similarity of the storage cells in NPD and Gaucher disease, we studied Gaucher plasma markers (chitotriosidase and CCL18) in two siblings homozygous for the R228C mutation in acid sphingomyelinase (ASM) and a type B course of NPD. The older sibling, first examined at the age of 9 months, showed marked hepatosplenomegaly and pulmonary involvement. The younger sibling has mild asymptomatic hepatosplenomgaly at the age of 5 months. Analysis of plasma specimens revealed markedly increased levels of chitotriosidase and CCL18 in the older sibling. In the younger child also, plasma chitotriosidase and CCL18 were clearly elevated above normal values almost immediately after birth and rapidly increased further. Histochemistry confirmed production of CCL18 by foam cells. In conclusion, plasma chitotriosidase and CCL18 may also serve as markers for the formation of pathological lipid-laden macrophages in type B NPD, in analogy to Gaucher disease. The availability of sensitive plasma surrogate markers may be of great value for monitoring the efficacy of enzyme supplementation therapy that is currently being developed.

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

“…Some studies suggest that in GD type 1 patients the accumulation of the immunogenic components in macrophages, such as ceramide and sphingolipids, causes cellular activation and consequently ChT secretion, which may mediate the immune response involved (Ballou et al 1996;van Eijk et al 2005). Increased ChT activity was also recorded in several other diseases, such as Niemann-Pick (Brinkman et al 2005), GM1 gangliosidosis , b-thalassemia (Barone et al 1999), sarcoidosis (Boot et al 2010), malaria (Barone et al 2003), atherosclerosis (Artieda et al 2003;Boot et al 1999), and fungal and bacterial infections (Iyer et al 2009;Labadaridis et al 1998). The role of ChT enzyme is unclear, but a possible role in defense against chitin-containing pathogens and host immune response has been suggested (Choi et al 2001;Di Luca et al 2007;Di Rosa et al 2005;Gordon-Thomson et al 2009;Malaguarnera et al 2005;van Eijk et al 2005).…”

Bacterial chitinases and chitin-binding proteins as virulence factors

“…moulds (Lee et al, 2008), exert numerous other effects in the mammalian host, including pathological conditions such as autoimmune, neurological or lysosomal storage diseases in humans (Brinkman et al, 2005;Boot et al, 1999;Bussink et al, 2006;Di Rosa et al, 2006;Lautner et al, 2011;Lee et al, 2011Lee et al, , 2012Mattsson et al, 2011;Sotgiu et al, 2008;Verbeek et al, 2010) and crystalline pneumonia in mice (Hoenerhoff et al, 2006;Liu et al, 2009). It will be of interest to examine such biologically relevant activities of mammalian chitinases and chitolectins in order to improve the understanding of the roles of similar proteins from bacterial pathogens.…”

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

“…6 Chit activity has been proposed as a biochemical marker of macrophage accumulation and activity in several lysosomal lipid storage diseases. [7][8][9][10] Little is known regarding the physiological function of CHIT-1, although its phagocyte-specific expression points to a role of the enzyme in innate immunity. [11][12] CHIT-1 mRNA expression is upregulated after stimulation by tumor necrosis factor alpha (TNF-a), interferon gamma (IFN-g), prolactin and lipopolysaccharide (LPS).…”