Abnormalities of erythrocyte membrane fluidity, lipid composition, and lipid peroxidation in systemic sclerosis - Evidence of free radical-mediated injury

Objective. To elucidate whether oxidative injury occurs in systemic scleros is (SSc) and whether it affects the erythrocyte membrane (EM) properties, Methods. EM fluidity and lipid composition (cholesterol:phospholipid molar ratio [C:PL], fatty acid composition) were studied in 52 patients with SSc and in 53 subjects without SSc (32 with primary Raynaud's phenomenon [RP] a nd 21 healthy subjects [controls]), Fluidity was measured as the fluorescen ce anisotropy of the hydrophobic fluorescent probe DPH (1,6-diphenyl-1,3,5- hexatriene). Lipid peroxidation products were determined as thiobarbituric acid-reactive substances (TBARS). Results. EM fluidity was significantly lower in SSc patients than in primar y RP patients and controls (P < 0.001). The EM C:PL molar ratio was signifi cantly higher in SSc patients than in primary RP patients and controls (P < 0.05). Levels of EM polyunsaturated n6 fatty acids (PUFA n6) mere signific antly lower in SSc patients than in primary RP patients and controls (P < 0 .001). TBARS were significantly increased in SSc patients compared with pri mary RP patients and controls (P < 0.001). Multiple regression analyses ind icated that the reduced EM fluidity was partly due to its greater C:PL mola r ratio, lower PUFA n6 content, and higher TBARS levels, EM fluidity was Po wer among patients with nailfold capillary loss (P < 0.001) and digital isc hemic ulcers (P < 0.05). EM lipid peroxidation products were higher among p atients with pulmonary involvement (bibasal pulmonary fibrosis [P < 0.05] a nd reduced levels of diffusing capacity for carbon monoxide [P < 0.001]) an d among patients who were positive for anti-topoisomerase I antibodies (P < 0.05) or negative for anticentromere antibodies (P < 0.001). Conclusion. Our findings support the idea that oxidative injury occurs in S Sc and that, through lipid peroxidation, it induces structural, and functio nal changes of the EM that may contribute to the development of the microva scular abnormalities that are seen in the disease.