Anticeramide antibody and butyrylcholinesterase in peripheral neuropathies.

Ceramide is a glycosphingolipid, a component of nerve and non neuronal cell membrane and plays a role in maintaining the integrity of neuronal tissue. Butyrylcholinesterase (BChE) is a multifunctional enzyme, its involvement in neurodegenerative diseases has been well established. Anticeramide antibody (Ab-Cer) and enzyme BChE have been implicated in peripheral neuropathies. The present study investigates whether there is an association between Ab-Cer and BChE activities and peripheral neuropathies. Patients included: human immunodeficiency virus associated peripheral neuropathy (HIV-PN, n=39), paucibacillary leprosy (PB-L, n=36), multibacillary leprosy (MB-L, n=52), diabetic neuropathy (DN, n=22), demyelinating sensory motor polyneuropathy (DSMN, n=13) and chronic inflammatory demyelinating polyneuropathy (CIDP, n=10). Plasma Ab-Cer was measured by indirect enzyme linked immune assay (ELISA) and BChE activity in plasma was measured by colorimetric method. Ab-Cer levels were significantly elevated in MB-L and DN as compared to healthy subjects (HS). BChE levels were significantly higher in MB-L and DN as well as in HIV and HIV-PN. There is no significant difference in either Ab-Cer or BChE levels in DSMN and CIDP. Elevated plasma Ab-Cer and BChE levels may be considered significant in the pathogenesis of neuropathies. The variation in concurrent involvement of both the molecules in the neuropathies of the study, suggest their unique involvement in neurodegenerative pathways.

High levels of plasma interferon gamma and +874T/A gene polymorphism is associated with HIV-TB co-infection.

OBJECTIVE: Tuberculosis (TB) is one of the most frequent opportunistic infections in HIV patients leading to increased morbidity and death rate. This study was carried out to investigate the role of the cytokines IFN-γ and TNF-α level and their single nucleotide polymorphisms (SNPs) in HIV-TB co-infection. METHODS: 247 HIV-TB (124 HIV-pulmonary TB, 123 HIV-extra pulmonary TB), 126 HIV positive individuals without tuberculosis and 129 healthy subjects (HS) were included to measure plasma levels of IFN-γ and TNF-α by sandwich ELISA and One way ANOVA statistical analysis was carried out among the groups. The SNPs of TNF-α-308 G/A, -238 G/A and IFN-γ+874 T/A were also investigated using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). The frequencies between the groups were compared by Pearson's chi square statistical analysis. RESULTS: Plasma IFN-γ and TNF-α were significantly elevated in HIV-TB and TB (p<0.05) as compared to those in HS group. There was significant association between IFN-γ+874 'A' allele and AA genotype in HIV-TB groups compared to HS and HIV (p<0.05) and no such association was found for TNF-α-308 and -238. The plasma cytokine levels of TNF-α and IFN-γ reveals no significant association with levels of IFN-γ+874 T/A, TNF-α -308 G/Aand-238 G/A genotypes in any of the study groups. CONCLUSION: In conclusion, the present study revealed elevated plasma IFN-γ and its +874 'A' allele are associated with HIV-TB co-infection indicating 1.6 times increased risk for TB susceptibility. Elevated TNF-α levels in TB and HIV-TB suggest its involvement in TB pathogenesis.

Association of tumor necrosis factor-alpha and interferon gamma gene polymorphisms and their plasma levels in leprosy, HIV and other peripheral neuropathies.

OBJECTIVE: Mycobacterium leprae and Human Immunodeficiency Virus (HIV) are causative agents known to be involved in nerve damage in leprosy and HIV-peripheral neuropathy (HIV-PN) respectively. Among other peripheral neuropathies the most common is diabetic neuropathy, which is metabolically induced. The proinflammatory cytokines TNF-α and IFN-γ have been implicated in the pathogenesis of peripheral neuropathy. The association between the plasma levels of these cytokines and their single nucleotide polymorphisms (SNPs) were investigated in leprosy neuropathy (LN), HIV-PN and other peripheral neuropathies (OPN). METHODS: Eighty-eight individuals with LN (PB=36; MB=52), 39 with HIV-PN, 52 patients with OPN, 101 HIV positive individuals without neuropathy (HIV) and 113 healthy subjects (HS) were included in the study. Plasma cytokine levels were measured by sandwich ELISA and one way ANOVA was carried out among the groups. SNPs of TNF-α- 308 G/A, -238 G/A and IFN-γ +874 T/A were investigated by amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Their frequencies were compared between groups by Pearson's chi squared test. RESULTS: Plasma TNF-α and IFN-γ was significantly increased in LN (p<0.05), HIV-PN (p<0.05) and OPN (p<0.05) as compared to HS. A significant association was found between IFN-γ +874 A/A genotype in LN (p<0.05; OR=7.9), HIV-PN (p<0.05; OR=8.9) and OPN (p<0.05; OR=8.9) as compared to HS. CONCLUSION: Elevated levels of plasma TNF-α and IFN-γ and the association of IFN-γ +874 A/A genotype SNP in LN, HIV-PN and OPN suggests a common involvement of these cytokines in susceptibility/pathogenesis of peripheral neuropathy.