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Neuropsychiatric manifestations have been reported in 30–60% of patients with systemic lupus erythematosus (SLE), with variable IgG synthesis in cerebrospinal fluid (CSF).1 In this study, we sought to examine intrathecal IgG synthesis measured qualitatively as the IgG index,2 calculated using the formula
(IgG CSF/IgG serum)/(albumin CSF/albumin serum),
and quantitatively as oligoclonal bands (OCBs) by isoelectric focusing (IEF)3 in patients with SLE with various neurological presentations, and to determine the cut‐off of the IgG index for the detection of these pathological IgG.
CSF results were retrieved from a database of 2902 samples using the keywords “SLE” or “lupus”. Only the first CSF sample taken before treatment for each neurological episode in each patient was analysed. Samples from traumatic subarachnoid haemorrhage were excluded. Cases were ascertained according to the American College of Rheumatology classification criteria.4 Neurological presentations were classified into neuropsychiatric SLE (NPSLE) according to the American College of Rheumatology criteria5 and other non‐NPSLE conditions. A total of 57 results from 54 patients were eligible for the analysis.
The 63 neurological presentations among the 57 neurological episodes were classified as inflammatory (n=49) and non‐inflammatory (n=13) according to the underlying pathogenesis determined by clinical features, MRI findings and response to immunosuppressive treatment. Table 11 shows the distribution of CSF OCBs, positive IgG index (>0.6) and the discrepancy between the two methods among these conditions. CSF OCBs were more frequently detected in inflammatory (26.5%) than in non‐inflammatory conditions, including focal NPSLE and non‐SLE‐related conditions (0%; p=0.05), but not for positive IgG index (p=1.0). The different rates of detection of CSF OCBs in NPSLE reflected heterogeneity in the underlying pathogenesis where microthrombi or vasculitis may cause damage to the blood–brain barrier.6,7,8 Although serum autoantibodies that cross react with antigens present in brain tissue have been shown to cause neuronal death through a damaged blood–brain barrier in the mouse model,9 our study suggested intrathecal synthesis of autoantibodies as another possible pathogenetic mechanism.
There was agreement between IEF and IgG index on the presence (17.5%, n=10) and absence (31.6%, n=18) of intrathecal IgG synthesis, giving a discrepancy rate of 50.9% (29/56). This discrepancy was found to correlate with the presence of serum hypogammaglobulinaemia or hypergammaglobulinaemia (r=0.86, p=0.004), which was present in 23 (40.3%) samples. This suggested a non‐linear relationship between the IgG ratio and the albumin ratio in the formula for IgG in these ranges of IgG.10 IEF is thus superior to the IgG index for detection in patients with SLE.
CSF OCBs were found to correlate with the IgG index in inflammatory neurological conditions with higher sensitivity using a higher cut‐off of the IgG index (0.81; fig 11).). The presence of CSF OCBs irrespective of the IgG index may suggest a specific immune response, whereas quantitatively increased IgG without OCBs might indicate a non‐specific polyclonal response. Studies on the specificities of CSF OCBs may provide clues to the underlying pathogenesis.
In conclusion, our study showed that intrathecal production of IgG was found in inflammatory NPSLE. IEF is the preferred method of detection. Other investigation results should be considered for diagnosis because of its lack of discriminative power for NPSLE and CNS infections.
CSF - cerebrospinal fluid
IEF - isoelectric focusing
OCB - oligoclonal band
NPSLE - neuropsychiatric SLE
SLE - systemic lupus erythematosus
Competing interests: None.