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D P D'Cruz

Publications and source records attributed to D P D'Cruz.

At least 19 recordsLinked to original sources
PubMed2007

Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.

OBJECTIVE: To determine the effects of primary antiphospholipid syndrome (PAPS)-derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays. METHODS: Anti-beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real-time PCR analysis or at the protein level by ELISA. RESULTS: A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti-beta(2)GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C). CONCLUSIONS: This study reveals a complex gene expression response in HUVEC to anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines, pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti-beta(2)GPI antibody-regulated genes could contribute to the vasculopathy associated with this disease.

Adult↗
PubMed2006

Low-dose intra-venous cyclophosphamide therapy in a patient with neurological complications of Behçet's disease.

Behçet's disease (BD) is a chronic relapsing-remitting inflammatory disorder of unknown origin, affecting multiple organs. Neurological involvement is one of the most devastating manifestations of BD and may be fatal. We report a 36-year-old woman with neuro-Behçet who was treated with low-dose pulse cyclophosphamide (St. Thomas' protocol) and methylprednisolone, with almost complete clinical remission.

Adult↗
PubMed2006

Mycophenolate mofetil treatment in resistant myositis.

OBJECTIVES: To assess the efficacy and tolerability of mycophenolate mofetil (MMF) in six patients with myositis refractory to conventional immunosuppressive therapy. METHODS: Six patients were identified from hospital notes. All had previously failed to respond to other immunosuppressive treatments. Efficacy was measured as changes in muscle strength, creatine kinase (CK) levels and prednisolone dose. RESULTS: The mean age of the group was 49.8 +/- 9.1 yrs, 6 (100%) were female and Caucasian. Patients had failed to respond to a median of 3 (range 1-3) immunosuppressive drugs. They received MMF for a mean of 22.3 +/- 18.9 months with a mean MMF dose of 1.6 +/- 0.5 g/day. The mean initial prednisolone dose was 13.7 +/- 7.7 mg and the mean follow up dose was 8.5 +/- 4.9 mg/day (P = 0.03). CK levels were reduced from mean 2395 IU/l +/- 1202.8 to 746.6 +/- 555.8 IU/l (P = 0.03). CONCLUSION: Our data demonstrate that MMF may be effective in myositis, previously unresponsive to conventional immunosuppressive drugs.

Adult↗
PubMed2006

Prevalence of the antiphospholipid syndrome in primary systemic vasculitis.

BACKGROUND: The antiphospholipid (APS or Hughes') syndrome, anticardiolipin antibodies (aCL), and the lupus anticoagulant (LA) are associated with systemic lupus erythematosus, malignancy, infection, and drugs. It has been described in patients with primary systemic vasculitis (PSV). OBJECTIVE: To determine the prevalence of APS in patients with PSV attending a vasculitis clinic and the prevalence of patients with positive aCL and/or the LA who do not fulfil the classification criteria for APS. METHODS: All case notes of patients attending the vasculitis clinic over a 12 month period were reviewed. Outpatients and inpatients were both included and were assessed for features of the APS and presence of aPL. Patients with positive aCL or LA tests were classified according to the significance of these results. RESULTS: Of 144 patients with PSV, 25 had positive aCL or LA on at least one occasion, representing a point prevalence of 17%. Of these, nine had definite APS (classified by the Sapporo criteria) and a further four patients had clinical and serological features of APS, although insufficient to satisfy the Sapporo criteria. Twelve had only positive aPL. CONCLUSION: The antiphospholipid syndrome, aCL, and the LA may occur in association with PSV.

Adolescent↗
PubMed2006

Atherogenesis in rheumatology.

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders.

Annexin A5↗
PubMed2005

Reduction of proteinuria with mycophenolate mofetil in predominantly membranous lupus nephropathy.

INTRODUCTION: Lupus membranous nephropathy (LMN) presents a difficult clinical problem as no particular treatment has been proven to be effective. Studies have shown good results with mycophenolate mofetil (MMF) in proliferative lupus nephropathy (LN) (WHO class III and IV disease). OBJECTIVES: To study whether MMF treatment was effective in membranous predominant LN in patients resistant to or intolerant of other immunosuppressive agents. PATIENTS AND METHODS: We retrospectively studied 10 patients with systemic lupus erythematosus who had biopsy-proven predominant LMN (six Vc patients and four Va or Vb patients). Previous treatments included cyclophosphamide, azathioprine, ciclosporin and corticosteroids. The following parameters were recorded at baseline and follow-up: blood pressure, ECLAM, proteinuria, serum albumin and creatinine, routine haematology and immunology. RESULTS: The study included eight women and two men, mean age 38.4 +/- 7.1 yr (range 30-49 yr). The racial distribution was as follows: five Caucasian, and five Black patients. The mean treatment time with MMF was 18.8 +/- 15.4 months (range 3-52 months). Twenty-four-hour urinary protein excretion was reduced from median 2.26 g (range 0-7.92 g) to median 0.66 g (range 0.08-3.85 g) at follow-up (P = 0.0039). Serum albumin increased significantly after treatment from median 29.5 g/l (range 14.0-42.0 g/l) to 33.5 g/l (range 23.0-40.0 g/l) at follow-up (P = 0.04). There were no significant changes in serum creatinine (P = 0.55). CONCLUSION: MMF is a potentially useful immunosuppressive agent in reducing the proteinuria associated with membranous predominant LN.

Adult↗
PubMed2005

Multiple sclerosis, neuropsychiatric lupus and antiphospholipid syndrome: where do we stand?

Multiple sclerosis (MS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are chronic, immune-mediated, relapsing-remitting disorders affecting young adults, the pathogenesis of which is still largely unknown. Neurological manifestations and magnetic resonance imaging (MRI) can be indistinguishable and there are no specific diagnostic tools. Treatment and prognosis are quite different. There is controversy about the prevalence and significance of antiphospholipid antibodies (aPL) in MS. A significant number of patients with APS/SLE are misdiagnosed as MS but evidence suggests they are distinct nosological entities. However, it is essential to differentiate them since APS may be responsive to anticoagulation. When assessing MS patients, clinicians should consider APS/SLE, especially if the MS has atypical features. A trial of anticoagulation might be worthwhile in some patients with atypical MS and consistently positive aPL.

Antibodies, Antiphospholipid↗
PubMed2005

Prevalence of an abnormal ankle-brachial index in patients with primary antiphospholipid syndrome: preliminary data.

OBJECTIVES: To evaluate the prevalence of abnormal ankle-brachial indexes (ABIs), their relationship with other cardiovascular risk factors and/or the presence of antiphospholipid antibodies (aPL), and the clinical use of the ABI in patients with primary antiphospholipid syndrome (primary APS). METHODS: An 8 MHz Doppler probe was used in the arms and legs to assess the ABI in 43 patients with primary APS (mean (SD) age 40.2 (7.9) years) and 49 healthy subjects (aged 41.0 (11.7)) matched for age and sex. Data on traditional cardiovascular risk factors, such as hypertension, hypercholesterolaemia, presence of diabetes mellitus, nephrotic syndrome or renal failure, smoking, and other variables, were collected at that time for all subjects. A ratio of the highest blood pressure from the posterior tibial or pedal arteries of each leg to the highest blood pressure from the brachial arteries <1.00 was considered abnormal. RESULTS: Abnormal ABIs were found in 8/43 (19%) patients with primary APS and 2/49 (4%) controls (p = 0.026). No correlation between abnormal ABI and traditional cardiovascular risk factors nor with the presence of aPL was found. CONCLUSION: Abnormal ABIs are more common in primary APS than in healthy controls, possibly indicating a subclinical atherosclerotic process in these patients.

Adult↗
PubMed2005

Livedo reticularis and pregnancy morbidity in patients negative for antiphospholipid antibodies.

BACKGROUND: Livedo may be an independent risk factor for pregnancy morbidity, additional to the known risks associated with the presence of antiphospholipid antibodies (aPL). OBJECTIVE: To determine the prevalence of pregnancy related morbidity in patients with widespread livedo reticularis who are persistently negative for aPL. PATIENTS AND METHODS: 52 patients with widespread livedo reticularis were studied: 31 fulfilled ACR criteria for SLE, 21 had a lupus-like illness; all were negative for aPL. All patients had livedo (racemosa or reticularis type) on their extremities, trunk, and/or buttocks. RESULT: 33 (63%) patients had pregnancy related morbidity. 22 patients had up to 9 miscarriages, 15 patients had >3 miscarriages, 2 had 2 miscarriages, 4 had a fetal death (>10 weeks), 17 had pre-eclampsia, and 4 patients had premature delivery. 19 patients had no pregnancy related morbidity. Overall morbidity was similar in the patients with lupus and lupus-like disease. CONCLUSION: Pregnancy related morbidity in lupus is known to be associated with the presence of aPL. This study suggests that pregnancy loss may also be independently associated with widespread livedo reticularis in patients who are aPL negative. A larger study is needed.

Abortion, Habitual↗
PubMed2005

Renal manifestations of the antiphospholipid syndrome.

Renal thrombotic manifestations have been reported since the earliest descriptions of the antiphospholipid (Hughes) syndrome (APS). The spectrum of clinical features associated with antiphospholipid nephropathy continues to widen. This review will highlight recent developments such as the prevalence of hypertension, livedo reticularis and renal artery stenosis as well as the ultrastructural changes seen in antiphospholipid nephropathy. The increasing risks of renal transplantation in antiphospholipid antibody positive patients is also discussed leading some authors to question whether these patients should undergo transplantation at all.

Antiphospholipid Syndrome↗
PubMed2005

MALToma and lupus.

We present two patients with low-grade non-Hodgkin MALT lymphoma (mucosa-associated lymphoid tissue) occurring years before clinical evidence of autoimmune disorders. While the strong association between autoimmune disorders, in particular Sjögren's syndrome and MALToma, is well described, the developement of MALToma years before the onset of an autoimmune disease is very unusual.

Adult↗
PubMed2005

Mycophenolate mofetil in systemic vasculitis.

The systemic vasculitides are a group of potentially life-threatening multi-system autoimmune connective tissue diseases characterized by vascular inflammation. The gold standard therapies include corticosteroids and cyclophosphamide as induction therapy and other agents such as azathioprine and methotrexate to maintain remission. Mycophenolate mofetil (MMF) is increasingly being used in autoimmune disorders and this article reviews the use of this agent in the systemic vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗