59 research outputs found

    Anna Lisa Wärnlöf

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    Anna Lisa Wärnlöf [Elektronisk resurs]

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    The role of Plasmodium falciparum var genes in malaria in pregnancy

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    Sequestration of Plasmodium falciparum-infected erythrocytes in the placenta is responsible for many of the harmful effects of malaria during pregnancy. Sequestration occurs as a result of parasite adhesion molecules expressed on the surface of infected erythrocytes binding to host receptors in the placenta such as chondroitin sulphate A (CSA). Identification of the parasite ligand(s) responsible for placental adhesion could lead to the development of a vaccine to induce antibodies to prevent placental sequestration. Such a vaccine would reduce the maternal anaemia and infant deaths that are associated with malaria in pregnancy. Current research indicates that the parasite ligands mediating placental adhesion may be members of the P. falciparum variant surface antigen family PfEMP1, encoded by var genes. Two relatively well-conserved subfamilies of var genes have been implicated in placental adhesion, however, their role remains controversial. This review examines the evidence for and against the involvement of var genes in placental adhesion, and considers whether the most appropriate vaccine candidates have yet been identified

    Sleepiness or fatigue? Can we detect treatable causes of tiredness in primary Sjogren's syndrome?

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    Objective. To study the prevalence of fatigue and daytime sleepiness in primary SS (pSS) and analyse predicting sleep disturbing factors and other potential determinants of fatigue and sleepiness. Method. Seventy-two consecutive pSS patients and 59 age-matched healthy controls were compared. Assessment instruments were profile of fatigue (ProF), visual analogue scale fatigue, Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale, restless legs syndrome (RLS) Diagnostic Criteria and Lund University Sleep Questionnaire. In addition, markers of immune disturbance, inflammation and disease activity using the European League Against Rheumatism SS Disease Activity Index were analysed in patients. Results. Fatigue, especially somatic fatigue, is the main problem for pSS patients. Sleepiness is a minor problem. Patients had significantly more often anxiety, nocturia and woke up more frequently during the night than controls. The factors that predicted daytime fatigue in pSS patients were anxiety and nightly awakenings due to pain. Nocturia was frequent but was not associated with fatigue or sleepiness. RLS, depression and sicca symptoms contributed to fatigue in the univariate regression analysis only. Conclusions. This is the first study demonstrating not only the presence of disturbed sleep, but also that nightly musculoskeletal pain and other sleep disturbing factors and anxiety significantly influence fatigue. Management strategies aimed at these aspects should therefore be included in future trials for treatment of fatigue in pSS

    A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern

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    The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype

    Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study

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    Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by approximately 60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcripts

    Osteoporosis-related fractures in men and women with established and early rheumatoid arthritis: predictors and risk compared with the general population

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    Abstract Objectives To study the risk of osteoporosis-related fractures in a community-based sample of men and women with rheumatoid arthritis (RA) overall, as well as early (< 1 year of disease duration, follow-up time maximum 10 years) and established (RA diagnosis since ≥ 5 years on July 1, 1997) RA, compared with the general population. To study potential risk factors for fractures in patients with RA from baseline questionnaire data. Methods A community-based cohort of patients with RA (n = 1928) was studied and compared to matched general population controls. Information on osteoporosis-related fractures (hip, proximal upper arm, distal forearm and vertebral fractures) during the period July 1, 1997 to December 31, 2017 was obtained by linkage to the Swedish National Inpatient Register and the Cause of Death Register. The incidence of fractures was estimated in patients and controls. Cox regression models were used to assess the relation between RA and the risk of fractures and to assess potential predictors of fractures in RA patients. Analyses were stratified by sex, and performed in all patients with RA, and in subsets with early and established RA. Results The overall incidence of osteoporosis-related fractures in the RA cohort was 10.6 per 1000 person-years (95% CI 9.31; 12.0). There was an increased risk of fractures overall in both men (hazard ratio (HR) 1.55, 95% CI 1.03; 2.34) and women (HR 1.52; 95% CI 1.27; 1.83) with RA compared to controls, with significantly increased risk also in the hip. No increased risk of osteoporosis-related fractures overall was seen in patients with early RA (HR 1.01, 95% CI 0.69; 1.49). Higher age, longer duration of RA, higher HAQ scores and higher scores in the visual analogue scale for global health were predictors of fractures. Conclusion Both men and women with RA were at increased risk of osteoporosis-related fractures. Patients with early RA did not have significantly increased risk during the first 10 years of disease in this study
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