Andrew P. Cairns

Reduced expression of CD44 on monocytes and neutrophils in systemic lupus erythematosus: relations with apoptotic neutrophils and disease activity

BACKGROUND Increased numbers of apoptotic neutrophils, and impaired monocyte/macrophage clearance of apoptotic cells, have been demonstrated in systemic lupus erythematosus (SLE). CD44 is implicated in the clearance of apoptotic neutrophils. OBJECTIVE To determine the expression of CD44 on peripheral blood monocytes and neutrophils in SLE, and examine the relations with disease activity and numbers of circulating apoptotic neutrophils. METHODS Peripheral blood was sampled from 31 patients with SLE, 19 healthy normal subjects, and 19 patients with rheumatoid arthritis (RA). Monocyte and neutrophil density of surface CD44 expression was determined by immunofluorescence labelling and flow cytometry, and results expressed as mean channel fluorescence (MCF) values. Neutrophil apoptosis was measured by morphology in 15 patients with SLE, nine with RA, and six normal subjects. RESULTS Monocyte CD44 expression was significantly lower in SLE (median MCF 4.71) than in healthy normal subjects (median MCF 5.61) and controls with RA (median MCF 5.39). Neutrophil CD44 expression was also significantly lower in SLE (median MCF 1.95) than in healthy normal subjects (median MCF 2.37) and controls with RA (median MCF 2.60). Monocyte, but not neutrophil, CD44 expression correlated negatively with the percentage of apoptotic neutrophils. There was no significant correlation of monocyte or neutrophil CD44 expression in SLE with disease activity or damage. CONCLUSIONS Monocyte and neutrophil CD44 expression is reduced in SLE, and this may contribute to the impaired recognition and clearance of apoptotic neutrophils by monocyte derived macrophages.

The CD14+ CD16+ monocyte subset in rheumatoid arthritis and systemic lupus erythematosus

Abstract Most human peripheral blood monocytes strongly express surface CD14, but not CD16 (CD14++/CD16–). A smaller group of monocytes express lower levels of CD14 and also express CD16 (CD14+/CD16+). This subgroup has different functional characteristics and is expanded in a number of disease states. We aimed to determine the percentage of circulating CD14+/CD16+ monocytes in rheumatoid arthritis and systemic lupus erythematosus (SLE) and relate this to disease measures. Peripheral blood was sampled from 31 SLE patients, 19 rheumatoid arthritis patients, and 19 healthy controls. The percentage of CD14+/CD16+ monocytes was determined by immunofluorescence labelling and dual colour flow cytometry. The percentage of CD14+/CD16+ monocytes was significantly lower in rheumatoid arthritis (median 4.90%) than in normal subjects (median 7.30%, P=0.014),and in rheumatoid arthritis than in SLE patients (median 9.40%, P=0.009). The percentage of CD14+/CD16+ monocytes in SLE was not significantly different from that in healthy subjects. This lower percentage of CD14+/CD16+ monocytes in rheumatoid arthritis may be important in the pathogenesis of this disease.

A systematic review of the effects of dynamic exercise in rheumatoid arthritis

Exercise is commonly used in the management of patients with rheumatoid arthritis (RA); however, there is little consensus in the literature to support its use. This systemic review aimed to determine the effects of dynamic exercise on patients with RA. A systematic search of Medline (1949–2007), Cinahl (1982–2007), Embase (1974–2007) and Cochrane library was performed for randomised-controlled trials using the keywords “rheumatoid arthritis” and “exercise” or “training” or “sport”. The methodological quality of studies was assessed using a ten-point scale. Eighteen papers relating to 12 different studies met inclusion criteria. The mean methodological quality score was 6.9/10. Studies using aerobic training, strength training and combinations of both were included. Patients with early, stable, and active RA were studied. A number of studies reported improvement in muscle strength, physical function and aerobic capacity with dynamic exercise. Some studies also reported improvements in disease activity measures, and small improvements in hip bone mineral density. One study reported significantly less progression of small joint radiographic damage of the feet in the dynamic exercise group. However, one study also reported worse large joint radiographic damage in patients using dynamic exercise who had pre-existing large joint damage, though this was a retrospective analysis. No studies reported worse outcomes for function, disease activity or aerobic capacity with dynamic exercise. Cardiovascular outcomes were not reported in any study, and no data were presented to assess the effect of exercise on patients with significant underlying cardiovascular disease. This systematic review suggests that the majority of patients with RA should be encouraged to undertake aerobic and/or strength training exercise. Exercise programmes should be carefully tailored to the individual, particularly for patients with underlying large joint damage or pre-existing cardiovascular disease.

Diagnosis and management of ankylosing spondylitis.

Ankylosing spondylitis is a chronic inflammatory rheumatic disorder that primarily affects the axial skeleton. Sacroiliitis is its hallmark, accompanied by inflammation of the entheses (points of union between tendon, ligament, or capsule and bone) and formation of syndesmophytes, leading to spinal ankylosis in later stages. Prevalence estimates vary between 0.1% and 2% in different populations.1 The male:female ratio is around 5:1, and the peak age of onset is at 15-35 years. Because of its insidious nature, the diagnosis is sometimes delayed until late stages of the disease. Until recently, treatment has been limited to non-steroidal anti-inflammatory drugs and physiotherapy, but the development of cytokine inhibitors that inhibit the activity of tumour necrosis factor α has been an important advance in treatment. We searched Medline for clinical trials and reviews using the keywords “ankylosing spondylitis,” “treatment,” “physiotherapy,” “NSAIDs,” “DMARDs,” “anti-TNF,” and “biologics.” The most commonly used criteria for the classification of ankylosing spondylitis were developed in 1966 and modified in 1984.23 They are: 1. Low back pain of at least three months duration with inflammatory characteristics (improved by exercise, not relieved by rest) 2. Limitation of lumbar spine motion in sagittal and frontal planes 3. Decreased chest expansion (relative to normal values for age and sex) 4. Bilateral sacroiliitis grade 2 or higher 5. Unilateral sacroiliitis grade 3 or higher. Definite ankylosing spondylitis is said to be present when the fourth or fifth criterion presents with any clinical criteria. However, radiological sacroiliitis may not develop for many years, and the development of new criteria (including magnetic resonance imaging) has been proposed to allow confirmation of the diagnosis in patients with early disease (see below).4 ### History The key point in a patients history is inflammatory back pain.5 This typically presents as low back pain and stiffness of insidious onset that is worse first …

TNF inhibitors for ankylosing spondylitis in the real world.

Sir, Anti-TNF therapies have revolutionised the treatment of ankylosing spondylitis. Three diVerent anti-TNF drugs are currently available: etanercept, inXiximab and adalimumab. To date 44 patients (38 male) with ankylosing spondylitis have been treated with anti-TNF agents in our unit and we have reviewed the data available on these patients from 1999 to May 2006. The median age of patients being treated with TNF inhibitors is 48 years. The median time in years from diagnosis until Wrst treatment with TNF inhibitor in this cohort was 17 years. Thirty-nine patients continue on treatment. The median duration of treatment, irrespective of change of agent, is 18 months. Two stopped because of chest infection, one of whom died. One patient stopped because of safety concerns (poor compliance). Two patients have had treatment suspended: One due to an anaphylactic reaction to inXiximab, and one due to recurrent ENT infections. First line drugs used were: inXiximab 26/44 (59.1%), adalimumab 10/44 (22.7%), etanercept 8/44 (18.2%). 28/44 (63.6%) patients had a good clinical response, as judged by their rheumatologist, to their Wrst TNF inhibitor: inXiximab 17/26 (65.4%), adalimumab 6/10 (60.0%), etanercept 5/8 (62.5%). Thirteen (29.5%) patients were felt to have had an inadequate clinical response to the initial drug and were switched to an alternative treatment. Four (9.1%) patients failed two consecutive drugs and were switched to a third treatment. Of the 28 patients with a good initial clinical response, median BASDAI, BASMI, ESR and CRP results were available for 82.1, 75, 92.9 and 92.9%, respectively as shown in Table 1. Ten patients have had their drugs temporarily withheld on at least one occasion over their treatment period. The commonest reasons for withholding treatment were suspected urinary tract infection, upper and lower respiratory tract infections, and conjunctivitis (7 receiving inXiximab, 2 etanercept, 1 adalimumab). Three patients have had recurrent infections necessitating frequent missed dosings and further investigation. In conclusion anti-TNF therapies have been initially eVective for a large proportion of our patients with ankylosing spondylitis. However, a signiWcant minority do not respond to one or more anti-TNF drug. Initial response rates were broadly comparable between the three anti-TNF drugs. Infections were the commonest reported reasons for withholding treatment. Many patients treated were felt to have had a good clinical response by their treating rheumatologist. This was reXected in a reduction in their inXammatory markers, but