摘要：

Neurologic manifestations occur in up to 70% of patients with systemic lupus erythematosus (SLE) and in 20% of patients with Sjgren's syndrome (SS) and are associated with significant morbidity. There is as yet no biologic marker that specifically indicates neurologic involvement in rheumatic diseases. In the literature to date, the association between nervous system manifestations of SLE and autoantibodies against ribosomal P proteins and N-methyl-Daspartate receptor has been inconsistently demonstrated (1). Transverse myelopathy is a rare but serious condition reported in patients with SLE and SS (2,3). In sera from some of these patients, an IgG autoantibody marker, called NMOIgG, has been recently detected (4,5). NMO-IgG was initially identified by immunohistochemistry using brain tissue in sera from patients with neuromyelitis optica (NMO; also known as Devic's disease), a severe demyelinating disorder of the central nervous system (CNS) that primarily affects the spinal cord and the optic nerves (6). In patients presenting with isolated longitudinally extensive transverse myelitis (LETM) involving at least 3 vertebral segments, as revealed using magnetic resonance imaging, and in patients with recurrent optic neuritis (ON), the presence of NMO-IgG indicates severe disease course with frequent relapses (7,8). NMO-IgG is not detectable in the sera of patients with multiple sclerosis (MS) (6). The antigenic target of NMO-IgG is aquaporin-4 (AQP-4), the most abundant water channel in the CNS (9). To detect these autoantibodies, assays employing recombinant AQP-4 have been repeatedly shown to be more sensitive than immunohistochemistry in CNS tissue (10). In order to evaluate the significance of NMO-IgG/ AQP-4 antibodies as potential markers of neurologic involvement in rheumatic conditions, we collected serum samples from patients with SLE (n 48) and SS (n 44), 28 and 22 of whom showed neurologic manifestations, respectively (Table 1). All patients fulfilled the American College of Rheumatology (ACR) classification criteria for SLE and SS (11,12). SLE patients with neurologic involvement fulfilled the ACR case definitions for neuropsychiatric lupus syndromes (13). Blood was drawn from 3 SLE patients (2 with LETM and 1 with LETM and recurrent ON) within 7 days of onset of a relapse. In the other SLE subsets, the time intervals between the serum sampling and the onset of the first neurologic symptoms or, in cases of relapses, the onset of the last relapse were as follows: TM, 1 year; LETM, 1–7 years (median 4 years); recurrent ON, 1 year; chorea, 1 year; psychosis/depression, 4–20 years (median 9.5 years); seizure disorders, 13 and 20 years. The duration of symptoms in SLE patients with polyneuropathy was 2–12 years (median 5 years). In patients with SS, time intervals were 7 and 8 years in 2 patients with TM and concomitant monophasic ON, 5 years in 1 patient with TM alone, and 13 years in both patients with LETM. Symptoms were present for 1–8 years (median 3 years) in SS patients with polyneuropathy. Samples were analyzed both by immunohistochemistry using native primate cerebellum, cerebrum, and optic nerve tissue sections and, for the first time in patients with SLE and SS, by means of a recombinant immunofluorescence assay (rIFA) using AQP-4–transfected HEK cells fixed in formalin. In direct comparison with the original procedure for the detection of NMO-IgG as described by Lennon et al (6), the rIFA exhibited an increase in sensitivity of 12.5% (overall sensitivity 78.1%; specificity 100%) in an earlier study based on 183 samples from NMO patients and relevant neurologic disease controls, including MS (14). Serum samples were classified as being positive or negative for NMO-IgG/AQP-4 antibodies by 2 independent investigators who were unaware of the clinical data. Testing was performed for diagnostic purposes in all cases. In SLE and SS, NMO-IgG/AQP-4 antibodies were found exclusively in patients with neurologic involvement comprising LETM or recurrent ON (Table 1). In the SLE cohort, autoantibodies against AQP-4 we

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