IntroductionThe induction of antinuclear antibodies (ANAs) or anti-double-stranded (ds) -DNA antibodies (Abs) after infliximab (IFX) therapy in rheumatoid arthritis (RA) is a well-known phenomenon, but the correlation of such Abs with the clinical response to IFX has not yet been determined. The aims of this retrospective observational study were to examine the prevalence of positive ANA and anti-ds-DNA Abs before and after IFX therapy in patients with RA and to investigate whether an increased titer of such Abs is associated with the clinical efficacy of IFX.MethodsOne hundred eleven RA patients who had received IFX were studied. ANA (indirect immunofluorescence with HEp-2 cells) and anti-ds-DNA Abs (Farr assay) results were examined before and after IFX therapy.ResultsThe overall clinical response assessed by EULAR response criteria was as follows: good response in 55%, including remission in 38%; moderate response in 18%; and no response (NOR) in 27%. The positivity of ANA (≥ 1:160) and anti-ds-DNA Abs significantly increased from 25% to 40% (P = 0.03) and from 3% to 26% (P < 0.001) after IFX, respectively. EULAR response differed significantly according to the ANA titer before IFX (P = 0.001), and the efficacy of IFX became worse as the ANA titer before starting IFX increased. Furthermore, the differences in the clinical response of the ANA titer before IFX ≤ 1:80 and ≥ 1:160 were significant (good, moderate, and no response were 66%, 9%, and 25% in ≤ 1:80 group versus 26%, 33%, 41% in ≥ 1:160 group, respectively; P < 0.001). In 13 patients whose ANA had increased after IFX, 10 showed NOR, only one showed a good response, and none reached remission. These clinical responses were significantly different from ANA no-change patients. In 21 patients with positive anti-ds-DNA Abs after IFX, 16 showed NOR, only two showed a good response, and none reached remission.ConclusionsThe present study suggests that the ANA titer before starting IFX predicts the clinical response to IFX. The increased titers of ANA or anti-ds-DNA Abs after IFX may be useful markers of NOR.

CSF anti-U1RNP Ab positivity is associated with increased level of CSF IFN-α. MCP-1 levels correlated with CSF anti-U1RNP Ab levels, whereas the increased CSF MCP-1 was not specific to CSF anti-U1RNP Ab-positive NPSLE.

Background Autoantibodies (auto Abs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). It is suggested that anti- N-methyl D-aspartate receptor NR2 subunit (NR2) Ab can develop NP manifestation after blood–brain barrier (BBB) abruption. We also reported the association between NPSLE and CSF anti-U1RNP Ab. In the present study, combined effects of CSF anti-NR2 and anti-U1RNP Abs on IMs in patients with NPSLE were examined. Methods CSF samples were collected from 69 patients with NPSLE and 13 non-NPSLE controls. CSF anti-NR2 and anti-U1RNP Abs were determined using ELISA. Levels of IL-6, IL-8, and monokine induced by IFN-γ (MIG) in CSF were measured by quantitative multiplex cytokine analysis. Results CSF IL-6 levels were higher in CSF anti-NR2-positive than in CSF anti-NR2-negative patients ( p = 0.003) and non-NPSLE controls ( p = 0.015) and were positively correlated with anti-NR2 titer ( r = 0.42). CSF IL-8 levels were higher in CSF anti-U1RNP-positive than in CSF anti-U1RNP-negative patients ( p = 0.041). CSF MIG levels were more elevated in CSF anti-NR2-positive ( p = 0.043) and anti-U1RNP-positive patients ( p = 0.029) than in non-NPSLE controls. Additionally, in double positive (DP; both anti-NR2 and U1RNP Ab positive) group, CSF IL-6 and MIG levels were significantly higher than in the double negative (DN; both anti-NR2 and U1RNP Ab negative) group. However, combined effect of both Abs on IM elevation and clinical manifestation was not clear. Conclusions CSF anti-NR2 and anti-U1RNP Abs have different effects on the elevation of CSF IM levels in patients with NPSLE. Additional effect of anti-U1RNP Abs on anti-NR2 Ab-mediated NP manifestation, however, was not recognized in our study.

BackgroundAutoantibodies (auto Abs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). Previous studies indicated that anti-N-methyl d-aspartate receptor NR2 subunit (NR2) Abs have a pathogenic role in NPSLE by BBB abruption.Hirohata S, et al, Arthritis Res Ther, 2014 We also reported the association between NPSLE and CSF-anti-U1RNP Abs (Sato, et al, A and R, 2010).ObjectivesIn the present study, synergistic effects of these auto Abs, their associated IMs, and blood brain barrier (BBB) permeability are determined in NPSLE patients.MethodsCSF samples were collected from 69 of NPSLE patients at their acute phase and 13 of non-NPSLE control after obtaining the written informed consent. CSF anti-NR2 and anti-U1RNP Abs were determined by ELISA. CSF IL-6, IL-8, and monokine induced by IFN-γ (MIG) were measured by quantitative multiplex cytokine analysis. BBB permeability was evaluated by albumin quotient (Qalb).Results1) CSF IL-6 levels were higher in CSF anti-NR2 Ab +ve (70±178 pg/mL) than in -ve (11±32, p=0.02) patients and in controls (16±40, p=0.003) and positively correlated with anti-NR2 Ab titer (r=0.42, p=0.003). Anti-U1RNP Ab positivity was not associated with CSF IL6 elevation. 2) CSF IL-8 levels were higher in CSF anti-U1RNP Ab +ve than in –ve (270±862 vs. 52±177 pg/mL, p=0.04) patients. Anti-NR2 Ab positivity was not involved in CSF IL8 elevation. 3) CSF MIG levels were more elevated in both CSF anti-NR2 +ve (4483±11845 pg/mL, p=0.04) and anti-U1RNP Ab +ve (5519±13504, p=0.03) patients than in controls (115±125). 4) All the patients were divided into 4 groups: CSF anti-NR2 +ve/anti-U1RNP+ve (double positive [DP], n=9), anti-NR2 +ve/anti-U1RNP -ve (aNR2, n=15), anti-NR2 -ve/anti-U1RNP+ve (aU1RNP, n=9), and anti-NR2 -ve/anti-U1RNP -ve (double negative [DN], n=36). In comparison between DP and aNR2 groups, anti-U1RNP Abs had a synergistic effect on CSF IL-6 elevation (150±260 vs. 18±44 pg/mL, p=0.03) that is not directly associated with anti-U1RNP Ab positivity. In comparison with aNR2 group, both CSF IL-8 (543±1198 vs. 43±102 pg/mL, p=0.04) and MIG (10104±17 748 vs. 1111±2584 pg/mL, p=0.03) levels, which were positively correlated with CSF anti-U1RNP Ab titer, were more elevated in DP group. 5) Qalb was positively correlated with CSF IL-8 (r=0.51, p<0.0001) and MIG (r=0.44, p=0.0003), suggesting that CSF anti-U1RNP Ab positivity is involved in the BBB abruption. Actually, Qalb (x103) tended to be higher in DP than in aNR2 group (13±9 vs. 9±8, p=0.06) and CSF anti-NR2 Ab titer appeared to be more elevated in DP than in aNR2 group (81±47 vs. 57±21, p=0.06).ConclusionsThe present study suggested that anti-NR2 and U1RNP Abs have synergistic effects on CSF IL-6 elevation in patients with NPSLE. CSF IL-6 level was associated with anti-NR2 Ab titers, which depend on BBB permeability. CSF anti-U1RNP Ab-mediated IL-8 and MIG elevation may induce BBB abruption followed by anti-NR2 Ab penetration into CSF.References[1...