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Objective To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA). Methods The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation-maximization algorithm, and BLyS serum levels were analyzed using enzyme-linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). Results The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti–cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti–tumor necrosis factor (anti-TNF) agents had previously failed. In the whole series of seropositive patients in whom anti-TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77–117.39], P = 0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7–152.5], P = 0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2–7.8], P = 0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear. Conclusion BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti-TNF agents have failed.

OBJECTIVE: The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response. METHODS: The study analysed 212 RA patients. European League Against Rheumatism (EULAR) response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. RESULTS: The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 (response in 34/38 (89.5%) VV vs 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01), but not at month +4 (response in 32/37 (86.5%) VV vs 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09). Loss of response was observed only in VF and FF carriers ((VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)). Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anticyclic citrullinated peptide antibodies, previous treatment with ≤1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p

Background Digital ulcers (DU) affect 50% of systemic sclerosis (SSc) patients, representing a challenging clinical problem. Despite a high negative predictive value, capillaroscopic scores proposed to select patients at risk for DU show an inadequate positive predictive value, especially in patients without previous DU. Aim of this study To increase the predictive value for DU development of capillaroscopy, through a predictive risk chart taking into account capillaroscopic, demographic, and clinico-serological parameters. Patients and methods Two hundred and nineteen unselected SSc patients from 8 Italian Rheumatology Centers were consecutively enrolled during a 6-month period. Demographic, clinical, serological and instrumental data and capillaroscopy skin ulcers risk index (CSURI) were collected. Results A multivariate logistic regression analysis showed a significant positive association between DU appearance and male gender, DU history, altered CSURI, and ESR. A prediction risk chart of the development of DU within 6 months were built on the basis of the above parameters. According to the risk level, four risk classes were identified: low (≤19.3%); medium (>19.3%, ≤58.6%); high (>58.6%, ≤89.2%), and very high risk (>89.2%). Conclusions The systematic evaluation of the above parameters can be helpful to identify patients at risk to develop DU optimizing preventive vasoactive therapy.

A43-YEAR-OLDWOMAN presented with progressive left visual loss, gait impairment, and urinary incontinence. Examination revealed paraparetic gait, pyramidal deep tendon reflexes, and bilateral Babinskisign.Hererythrocytesedimentation rate was raised. Extensive diagnostic workup (including measurement of antinuclear antibody, extractable nuclear antigen, antineutrophil cytoplasmic antibody, antiphospholipid antibodies, angiotensin-convertingenzyme,and antibodiestoaquaporin-4)ruledout systemicorinfectiousvasculitis.The results of cerebrospinal fluid biochemicalandmicrobiologicalanalysiswerenegative.Oligoclonalbands were absent. Spinal magnetic resonanceimaging(MRI)disclosedacervicodorsal T2-hyperintense lesion withcervicaltractswelling(Figure, A); brain MRI showed acute ischemiclesionsinwatershedareasofthe left centrum semiovale (Figure, B). Magneticresonanceangiographyrevealed bilateral middle cerebral artery occlusion. Catheter angiography confirmed these findings (Figure, C) and evidenced narrowing of the left ophthalmic artery (Figure, D), posterior cerebral artery (Figure, E), and right anterior cerebralartery,withactivationofleptomeningeal collateral circulation. Althoughneuromyelitisopticaor multiple sclerosis are common in young women with this clinical onset, laboratory results, characteristicmultifocalintracranialvesselnarrowing or occlusion, and ischemic parenchymalinvolvementintheabsenceofknownvasculiticcausesled to the diagnosis of primary central nervous system (PCNS) vasculitis. After treatment with high-dose intravenous methylprednisolone sodium succinate followed by oral cyclophosphamide, the spinal lesion recovered within 2 weeks, whereas vascular MRI findings also persisted, unchanged, at 8-month follow-up. The patient regained the ability to walk independently, but mild visual and bladder dysfunctions persisted. COMMENT