Transcript profiling of CD16-positive monocytes reveals a unique molecular fingerprint.

CD16-positive (CD14(++) CD16(+) and CD14(+) CD16(++) ) monocytes have unique features with respect to phenotype and function. We have used transcriptional profiling for comparison of CD16-positive monocytes and classical monocytes. We show herein that 187 genes are greater than fivefold differentially expressed, including 90 genes relevant to immune response and inflammation. Hierarchical clustering of data for monocyte subsets and CD1c(+) myeloid blood dendritic cells (DCs) demonstrate that CD16-positive cells are more closely related to classical monocytes than to DCs. Reverse transcriptase polymerase chain reaction for ten genes with the strongest differential expression confirmed the pattern including a lower messenger RNA level for CD14, CD163, and versican in CD16-positive monocytes. The pattern was similar for CD16-positive monocytes at rest and after exercise mobilization from the marginal pool. By contrast, alveolar macrophages, small sputum macrophages, breast milk macrophages, and synovial macrophages all showed a different pattern. When monocyte-derived macrophages (MDMs) were generated from CD16-positive monocytes by culture with macrophage colony-stimulating factor in vitro, then the MDMs maintained properties of their progeny with lower expression of CD14, CD163, and versican compared with CD14(++) CD16(-) MDMs. Furthermore, CD16-positive MDMs showed a higher phagocytosis for opsonized Escherichia coli. The data demonstrate that CD16-positive monocytes form a distinct type of cell, which gives rise to a distinct macrophage phenotype.

Persistent clinical efficacy and safety of infliximab in ankylosing spondylitis after 8 years--early clinical response predicts long-term outcome.

OBJECTIVES: To report for the first time on the efficacy and safety of anti-TNF therapy after 8 years of follow-up in patients with active AS, and analyse possible short-term predictors for long-term clinical outcomes. METHODS: In this open-label extension of a randomized controlled trial, proportions of the initially included 69 patients with active AS were treated with infliximab 5 mg/kg i.v./6 weeks for 8 years. The last report was published after 5 years. All analyses were based on completers. RESULTS: Overall, 33 (48%) patients completed 8 years. Their mean (s.d.) BASDAI [2.6 (1.9)], BASFI [3.3 (2.6)] and BASMI [2.7 (2.4)] remained low at Year 8. At the end of Year 8, most patients were either in partial remission (n = 8, 24%) or had low disease activity (BASDAI < 3; n = 21, 64%). No new serious adverse events occurred within the past 3 years. Adverse events were the most frequent reason for dropout (56%). There were no differences between completers and dropouts at baseline, but the latter had higher BASFI values at dropout. No baseline parameter was associated with good long-term response to infliximab, but lower BASDAI levels after 12 weeks were predictive of a higher probability of partial remission [odds ratio (OR) 2.9, 95% CI 1.3, 6.3, P = 0.007], low disease activity (OR 1.7, 95% CI 1.2, 2.3, P = 0.005) or remaining on treatment (OR 0.79, 95% CI 0.61, 1.01, P = 0.06) after 8 years. CONCLUSION: Almost half of the initially treated patients remained on anti-TNF therapy for 8 years, and almost 90% were in partial remission or had low disease activity. Short-term response (low BASDAI at 3 months) is predictive of outcome after 8 years. Infliximab therapy was safe over 8 years.

Whole-body MR imaging in psoriatic arthritis: additional value for therapeutic decision making.

PURPOSE: In psoriatic arthritis (PsA) multiple locations may show inflammatory changes not always readily accessible to clinical exam. Often, clinical exam is inconclusive and the decision to initiate or adapt therapy is difficult. Whole body (WB)-MRI may help in this situation by providing a comprehensive overview of affected areas/joints. The purpose of this study was to make a proof of concept whether WB-MRI in psoriatic arthritis is feasible and can provide additional information compared to clinical examination alone with regard to therapeutic decision making in patients with PsA and inconclusive clinical situation. MATERIALS AND METHODS: 30 patients with PsA and diffuse musculoskeletal pain were examined. A WB-MRI protocol was implemented on a 1.5 Tesla scanner using coronal and sagittal STIR- (TR: 5800, TE: 54, matrix 384(2) pixels, FOV 400 mm) and pre- and steady-state-post-Gadolinium-VIBE sequences (TR: 9.82, TE: 4.53, matrix 384×307 pixels, FOV: 400 mm). MRI was evaluated for image quality and inflammatory findings by two readers in consensus and compared to clinical exam. RESULTS: The WB-MR-exam was well tolerated by all patients. Image quality was rated good to excellent in 26 of 30 patients (86.6%). WB-MRI detected significantly (p<0.001) more areas of synovitis/enthesitis than clinical exam except for the hands and feet. MRI was able to detect unknown destructive bony changes in 10 patients (53%). In 22 patients (73.3%) the therapy regimen was modified, in 18 patients (62%) TNF-alpha-inhibitors were started. CONCLUSION: Whole-body MRI (WB-MRI) may be integrated in the diagnostic work-up of patients with psoriatic arthropathy facilitating individual adaptation of therapeutic strategy.

Relapsing cutaneous leishmaniasis in a patient with ankylosing spondylitis treated with infliximab.

A 31-year-old man with ankylosing spondylitis, receiving treatment with infliximab, presented with a large progressive cutaneous ulcer at the right knee. Biopsies showed Leishmania amastigotes, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis showed Leishmania infantum as the causative agent. After treatment with miltefosine, the ulcer resolved completely, and infliximab was reinstituted because of progression of spondylitis. After 1 year, there was a recurrent ulcer at the same site being positive for Leishmania DNA by PCR. Local treatment with sodium stibogluconate resulted in complete regression. Cutaneous leishmaniasis should be added to the list of opportunistic infections associated with anti-tumor necrosis factor (TNF) treatment. Despite recurrences, antileish-manial treatment may be effective in cases without alternatives to anti-TNF therapy.