ELEVATED PLASMA-LEVELS OF REDUCED HOMOCYSTEINE IN COMMON VARIABLE IMMUNODEFICIENCY - A MARKER OF ENHANCED OXIDATIVE STRESS

Based on previous studies from our group, we hypothesized that enhance d oxidative stress in association with a persistent immune activation may be important in both the immunopathogenesis and certain clinical m anifestations in a subgroup of patients with common variable immunodef iciency (CVI). To explore this hypothesis further, we examined plasma levels of Lipid peroxidation, antioxidant vitamins and redox status of various thiol species in 20 CVI patients and 16 healthy control subje cts. We found significantly higher malondialdehyde (MDA) levels in pla sma from CVI patients than in healthy control subjects. Furthermore, i n a subgroup of CVI patients characterized by persistent immune activa tion in vivo (CVIHyper), we found significantly decreased levels of vi tamin E and beta-carotene. In the CVI patients, there was a significan t inverse correlation between MDA levels and levels of vitamin E and b eta-carotene. Finally, we found a marked elevation in plasma levels of reduced homocysteine in the CVI group, but no corresponding rise in p lasma levels of total homocysteine. In the CVI group, the high plasma levels of reduced homocysteine were significantly correlated with enha nced Lipid peroxidation and low levels of vitamin E. The results of th e present study further support a role for enhanced oxidative stress i n the immunopathogenesis of CVI. Furthermore, our finding of markedly elevated plasma levels of reduced homocysteine in CVI patients without simultaneous elevation of other homocysteine species suggests that th is disturbance in homocysteine metabolism may be related to enhanced o xidative stress.