Elevated plasma chitotriosidase activity in various lysosomal storage disorders

Abstract

Recently a striking elevation of the activity of chitotriosidase, an endo beta-glucosaminidase distinct from lysozyme, was found in plasma from patients with Gaucher type I disease (McKusick 230800). Plasma chitotriosidase originates from activated macrophages and this elevation is secondary to the basic defect in Gaucher disease. To investigate the specificity of this phenomenon, we have investigated 24 different lysosomal storage diseases. In 11 different diseases increased chitotriosidase activity in plasma was found (in 28% of the patients). None of these diseases showed elevations as high as in Gaucher disease. Chitotriosidase was not significantly elevated in plasma from 20 different non-lysosomal enzymopathies or in plasma from patients with infectious diseases associated with hepatomegaly. The results show that marked elevation of chitotriosidase activity in plasma appears to be specific for Gaucher disease. The data further suggest that elevated levels of chitotriosidase activity in plasma from patients with unexplained diseases may be indicative for a lysosomal disorder.

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).…”

A 24-bp duplication in exon 10 of human chitotriosidase gene from the sub-Saharan to the Mediterranean area: role of parasitic diseases and environmental conditions

“…4,5 In humans, Chit is synthesized by activated macrophages. Chit levels have been proposed as a biochemical marker of macrophage activation in several lysosomal diseases, 6 especially in Gaucher diseases or beta-glucocerebrosidase deficiency, 7 where uncleaved membrane glycolipids are stored in the macrophage cells. Moreover, Chit is increased in patients affected by malaria infection and in other hematological disorders where activated macrophages are involved.…”

“…Moreover, Chit is increased in patients affected by malaria infection and in other hematological disorders where activated macrophages are involved. [6][7][8][9] In keeping with the established antiparasitic function of homologous chitinases in plants, it is conceivable that human Chit might fulfill a role in the degradation of chitin-containing pathogens.…”

Dup-24 bp in the CHIT1 Gene in Six Mexican Amerindian Populations

“…However, one important caveat is the presence of individuals homozygous for dup-24 bp in CHIT1 who will require other biomarkers to follow up on their response to ERT (Guo et al 1995;Lee et al 2007;Manno et al 2014). The identification of this polymorphism should also be useful for establishing genetic relationships between populations.…”

“…This enzyme is proteolytically processed to a C-terminally truncated 39-kDa isoform characterized by hydrolase activity and is primarily thought to play a role in the body's defense against chitin-containing pathogens (Renkema et al 1997;Boot et al 1999). CHIT activity has been used in the diagnostic screening of several lysosomal storage diseases, in which this enzyme is usually highly elevated, making this enzyme a useful secondary biomarker for the treatment monitoring of Gaucher disease (OMIM 230800), Niemann-Pick disease (OMIM 257200), Krabbe disease (OMIM 245200), and thalassemia (OMIM 603141) (Guo et al 1995;Boot et al 1999).…”