Plasma samples from 70 patients with multiple sclerosis (MS), 41 patients with other neurological diseases (OND), and 38 healthy subjects were examined for anti-bodies against gangliosides GM1, GM3, GDla, GD1b, and GD3 using enzyme-linked immunosorbent assays. The percentages of subjects with increased anti-GM3 responses were significantly higher in the primary progressive MS (56.3%) and secondary progressive MS (42.9%) groups than in the relapsing-remitting MS (2.9%), healthy subject (2.6%), and OND (14.6%) groups. Elevated antiganglioside antibodies may be secondary to axonal damage or may be a cause of axonal damage and accumulating disability in progressive MS. In either case, they may serve as a marker of axonal damage in MS.Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Typically MS initially has a relapsing-remitting (RR) course; however, often this relapsing-remitting course eventually changes to a progressive one (secondary progressive [SP] MS). In 10 to 20% of cases of MS, the disease has a progressive course from onset (primary progressive [PP] MS). The cause of MS is unclear, but there is increasing evidence that it is an autoimmune disease. 1,2 Because primary demyelination is a characteristic pathological feature of MS, myelin components, particularly myelin proteins, are considered to be the likely target antigens. 1,2 Recently we have shown that patients with RRMS or SPMS, but not PPMS, have increased peripheral blood T-cell proliferative responses to a region of myelin proteolipid protein ) that is encephalitogenic in mice. 3 The lack of an increased Tcell response to this region of PLP in PPMS raises the possibility that the main target antigens in PPMS are not myelin antigens, but axonal antigens. 4 An immune attack directed primarily at axonal antigens could explain the progressive course of this form of MS, as the capacity for CNS axonal regeneration is much more limited than the capacity for CNS remyelination, which is likely to contribute to the recovery from attacks of RRMS. The transition from RRMS to SPMS could involve the spreading of the immune response from myelin to axonal antigens. 4 Gangliosides constitute an important group of axonal antigens and are also minor constituents of myelin. A number of studies have found increased amounts of antiganglioside antibodies in the sera or cerebrospinal fluid (CSF) of patients with MS compared with healthy subjects. [5][6][7][8][9][10][11][12] However, the significance of this is unclear, because in most studies the antiganglioside levels in MS patients were not compared with those in patients with OND 6,9,12 or, if they were compared, were not significantly different. 7,11 The only study that has compared antiganglioside antibody levels among the RR, SP, and PP forms of MS is that of Acarin and colleagues. 12 They found elevated serum antibodies against GM1, asialoGM1, and GDla significantly more frequently in PPMS than in RRMS or SPMS; however, the number of patients wit...
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