London Bridge Hospital

About: London Bridge Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Antiphospholipid syndrome & Systemic lupus erythematosus. The organization has 107 authors who have published 122 publications receiving 4523 citations.

Hepcidin, haemoglobin and ferritin levels in sickle cell anaemia.

Abstract: To the Editor: The variant haemoglobin S (HbS) results from substitution of valine for glutamic acid as the sixth amino acid of b-globin (1). Homozygous HbSS disease or sickle cell anaemia (SCA) is characterised by reduced concentration of haemoglobin in the blood, susceptibility to infections, recurrent vasoocclusion, tissue infarction and complications such as stroke, avascular necrosis of joints or nephropathy (2). Tissue hypoxia from vessel obstruction facilitates deoxygenation of HbS, its crystallisation, erythrocyte sickling and chronic haemolysis (3). Recurrent tissue damage from vessel occlusion leads to chronic inflammation, as evidenced by increased levels of C-reactive protein and other inflammatory markers, even in steady-state SCA (4). A major public health problem on a global scale, SCA affects millions of people worldwide and about 300 000 newborns every year (5). Although the genetic mutation (GAG GTG) is identical in all HbSS patients studied to date, marked individual variation in disease severity occurs. Previous investigations have shown that differences in b-globin gene haplotype (6), the number of aglobin genes (7, 8), HbF levels (6, 9), neutrophil count (10) and leucocyte adhesion molecule expression (11) affect the severity of SCA. However, the biological basis of the individual variation in clinical severity is not completely understood. The novel iron-regulatory peptide hormone hepcidin is made in the liver, and inhibits intestinal absorption as well as macrophage recycling of iron (12). The gene for hepcidin is regulated by anaemia, hypoxia and inflammation, and its urinary excretion is greatly increased in patients with iron overload and infection (13). All these conditions occur in SCA. There is evidence that hepcidin has a role in the pathogenesis of anaemia of chronic inflammation (14, 15). Recent reports indicate that increased hepcidin production in inflammatory states is mediated via interleukin-6 (14, 16, 17); a cytokine known to be increased in SCA (18). From the perspective that chronic inflammation occurs in sickle cell disease, it is pertinent to find out if increased hepcidin production contributes to anaemia in the disorder. It has been suggested that blood levels of hepcidin and ferritin may correlate because they are regulated by similar pathological stimuli (14). In anaemia of chronic inflammation, hepcidin production is increased up to 100-fold and this may account for the sequestration of iron in macrophages (15). Hepcidin also has microbicidal activity (19, 20). People with SCA are prone to infection: a classical cause of inflammation, and the commonest precipitant of vaso-occlusive crisis (2). Repeated vasoocclusive infarction causes complications such as stroke or avascular necrosis of joints, and organ dysfunction such as nephropathy from cumulative loss of functional parenchyma tissue. Considering that hepcidin has antimicrobial properties and a role in the pathogenesis of anaemia in chronic inflammatory states, the specific objective of this study was to find out if plasma concentration of this peptide hormone affects steady-state haemoglobin and ferritin levels, number of disease complications or infections in SCA. Following informed consent, venous blood samples were obtained from 40 HbSS adults in steady state and 30 HbAA, healthy, racially-matched controls with similar age and sex-distribution. We excluded HbSS patients who had pregnancy in the previous 2 months, HbF ‡10%, any other disease apart from SCA or sickle crisis in the previous 2 months. Hb genotype was determined by highperformance liquid chromatography. In SCA patients steady-state Hb level was measured with the Beckman Coulter GEN-S analyser (Coulter Electronics, Luton, UK). Patients with complications of sickle cell disease (e.g. stroke, avascular necrosis or renal impairment), or who had infection during the period of 1 yr preceding the date of blood sampling were noted. Plasma hepcidin concentration was measured by enzyme-linked immunoassay using a commercially available kit (DRG Diagnostics, Marburg, Germany). Ferritin levels were determined by enzyme-linked immunoflourescence with the Beckman Coulter Access analyser. Eur J Haematol 2005: 74: 86–88 All rights reserved Copyright Blackwell Munksgaard 2005

Hughes syndrome/APS. 30 years on, what have we learnt? Opening talk at the 14th International Congress on antiphospholipid antibodies Rio de Janiero, October 2013

Abstract: It is 30 years to the month since our initial publications describing the syndrome. Prior to 1983 there had been case reports of lupus patients who could have had antiphospholipid features. Possibly one of the earliest was a case described by William Osler in 1895 – a 40-year-old male with lupus who developed a stroke. My own interest stemmed from our work in the early 1970s on brain-reactive antibodies in cerebral lupus. In 1975, during a year ‘on loan’ from Hammersmith to the University of the West Indies in Jamaica, I became interested in ‘Jamaican neuropathy’ – a virus-induced myelopathy which, both clinically, as well as its frequently positive antinuclear antibodies and false-positive tests for syphilis, resembled ‘lupoid sclerosis’. I was influenced by the work of Joyce Rausch, here in the audience, focusing on the structural similarities between the DNA backbone and that of phospholipids. Perhaps there was a subset of antibodies which reacted with neuronal phospholipids? Back at Hammersmith, we set up assays for antiphospholipid antibodies (aPL) – work led by two of my research fellows, the late Aziz Gharavi andNigel Harris. We used cardiolipin, partly because of the ‘syphilis’ link, and partly, as my then-technician Chris Bunn recently reminded me, because we had a stock of unused cardiolipin in the lab. For me, the late 1970s and early 1980s were productive years. Our large clinics and regular all-day ward rounds soon picked up a strong clinical scent – that which we called at first the ‘anticardiolipin syndrome’. We changed the name two years later to the antiphospholipid syndrome (APS). I believe that those early descriptions have stood us in reasonably good stead – clinically, at least (Table 1). Our first international conference was held in 1984, followed by the second in 1986 after our move to St Thomas’ Hospital (Figure 1). Since then, APS conferences have been held every two to three years, culminating in today’s meeting in Rio, Brazil, with 650 attendees. In those intervening meetings, so much has been learnt.

Antiphospholipid syndrome (Hughes syndrome): 10 clinical topics.

Abstract: This year in Galveston, Texas, Silvia Pierangeli hosts the 13th International Congress on Antiphospholipid Antibodies. Twenty-six years after the first antiphospholipid syndrome meeting, the number of interested colleagues has multiplied, and the subject has become more scientifically understood. So also has the clinical picture. In this short contribution, I will highlight a number of clinical observations which may, or may not, contribute to our understanding of antiphospholipid syndrome.