From ANA-screening to antigen-specificity: an EASI-survey on the daily practice in European countries.

OBJECTIVES: One of the main goals of the European Autoimmunity Standardisation Initiative (EASI) is the harmonisation of test-algorithms for autoantibodies related to systemic autoimmune rheumatic diseases (SARD). METHODS: A questionnaire was used to gather information on methodology, interpretation, and the algorithm for detection of anti-nuclear antibodies (ANA) in relation to their antigen-specificity. The questionnaire was sent to 1200 laboratories in 12 European countries. RESULTS: The response rate was 47.2%. The results reveal not only apparent differences between countries, but also within countries. CONCLUSIONS: Awareness of these differences may as such already stimulate harmonisation, but the observed differences may also direct recommendations that may further contribute to achieving the EASI goal of harmonisation of autoimmune diagnostics for SARD.

Rescue of kidney function in a toddler with anti-GBM nephritis.

Anti-glomerular basement membrane (anti-GBM) nephritis is rare in childhood with few published cases. We report a 19-month-old boy with rapidly progressive glomerulonephritis (RPGN) due to anti-GBM nephritis. Treatment was started under 2 weeks after presentation and included plasma exchange, intravenous high-dose methylprednisolone, intravenous cyclophosphamide and mycophenolate as mainstay medication. The treatment was rapidly effective with immediate decrease in anti-GBM titres and plasma creatinine. Three years after presentation, the boy has normal kidney function, blood pressure and no residual disease. The successful outcome was likely due to the rapid recognition of the anti-GBM antibodies as the cause of RPGN and aggressive primary treatment.

[Doppler sonography of arteriovenous fistulas for haemodialysis]. / Ultralyddoppler ved arteriovenøs fistel for hemodialyse.

BACKGROUND: Permanent and reliable vascular access is of utmost importance for patients (with chronic renal failure) in need of haemodialysis. Autogenous arteriovenous fistula (AVF) on the forearm are robust and have the benefits of providing long-term access with relatively few complications. The main problem is insufficient blood flow due to stenoses requiring early intervention. The AVF therefore needs surveillance with regular clinical examination supplemented with imaging. In recent years Doppler sonography has gained an increasingly important role in the assessment of AVFs. This paper discusses AVFs and frequent complications and stresses the benefit of Doppler sonography in the planning and surveillance of AVFs. MATERIAL AND METHODS: The survey is based on literature retrieved from a PubMed search, and our experience from sonographic examinations of AVFs in the Central Hospital of Lillehammer, Norway. RESULTS: Doppler sonography is a non-invasive imaging modality without discomfort for the patient, and well suited for examination of AVFs. The method has a high sensitivity for detection of stenoses and other AVF-related problems, and can provide a detailed image of the course and diameter of blood vessels, with quantitative measurement of blood flow. Indications for Doppler sonography are preoperative mapping, assessment of fistula problems and maturity; it is also a useful method for continuous surveillance of fistulas. INTERPRETATION: Doppler sonography can be used for immediate treatment of patients with sudden AVF problems; and if necessary endovascular intervention or surgery can follow. Recent European guidelines recommend the method as a standard procedure before and after creation of an AVF. Doppler sonography should have a central position in a multidisciplinary teamwork on surveillance of patients with AVFs in need of haemodialysis.

The molecular basis for hereditary porcine membranoproliferative glomerulonephritis type II: point mutations in the factor H coding sequence block protein secretion.

Porcine membranoproliferative glomerulonephritis type II in piglets of the Norwegian Yorkshire breed is considered the first animal model of human dense deposit disease. Porcine dense deposit disease is caused by the absence of the complement regulator factor H in plasma. Here we report the molecular basis for this absence. Single nucleotide exchanges at position C1590G and T3610G in the coding region of the factor H gene result in amino acid exchanges at nonframework residues L493V and I1166R that are located within SCR 9 and SCR 20, respectively. Apparently the L493V mutation represents a polymorphism whereas the I1166R causes the physiological consequences a block in protein secretion. Expression analysis shows comparable mRNA levels for factor H in liver tissue derived from both affected and healthy animals. In affected piglets, factor H protein is detected in increased amounts in liver cells. Factor H accumulates inside the hepatocytes and is not released as shown by Western blot analysis and immunohistochemistry. These data demonstrate that single amino acid exchanges of two nonframework amino acids either alone or in combination block protein secretion of factor H. This observation is also of interest for other human diseases in which factor H is involved, such as human factor H-associated form of hemolytic uremic syndrome.