Ongoing projects in clinical chemistry

Oral immunotherapy with IgY for the prevention of bacterial and viral infections in humans

Researchers involved: Elin Nilsson, Hans Kollberg, Per-Erik Wejåker, Johan Stålberg, Audrey Niemann-Jönsson and Anders Larsson

Cystic fibrosis (CF) is a hereditary life-shortening disorder with repeated respiratory infections and malnutrition as main clinical manifestations. Chronic lung infections with Pseudomonas aeruginosa (PA) are major causes of morbidity and mortality. We have shown that we can reduce the number of pseudomonas infections in CF patients by oral immunotherapy with anti-pseudomonas IgY. The study includes more than 100.000 daily patient doses and is the world's largest study with IgY. We have received an orphan drug designation from EMEA. We also have initiated development of therapies against candida albicans and ESBL-klebsiella. We have received a grant from Uppsala Bio to conduct a clinical study on ESBL carriers in Uppland and an EU grant for a clinical multicenter study to prevent pseudomonas infections in CF patients. We are also performing studies on the use of avian antibodies to prevent ventilator associated pneumonia.

Serum half-life of pituitary gonadotropins is decreased by sulfonation and increased by sialylation in women

Researchers involved: Leif Wide and Karin Eriksson

The gonadotropins are secreted from the human pituitary as spectra of isoforms with different degrees of sulfonation and sialylation of the oligosaccharides, modifications suspected to determine their half-lives in the circulation. We found that the decline in LH and FSH during GnRH receptor blockade is associated with a decrease in sulfonated and increase in sialylated residues. The results indicate that both sulfonation and sialylation of the gonadotropins regulate their half-life in the circulation. The rapid disappearance of LH isoforms with two and three SO3-GalNAc residues suggests their removal by hepatic SO3-GalNAc-receptors similar to those in rodents. Episodic secretion of spectra of isoforms with different half-lives is expected to lead to continuous changes in gonadotropin isoform compositions in blood.

Studies of the role of prostasome in fertility and prostate cancer

Researchers involved: Göran Ronquist, Lena Carlsson, Gunnar Ronquist and Anders Larsson

We discovered the prostasomes more than 30 years ago and named them. The prostasomes with their complex membrane architecture have been assigned multifunctional features in the normal reproductive process. What is more, evidence has accumulated pointing to a role of prostasomes in the propagation of prostate cancer, based on the findings that also malignant prostate cells are able to produce and export prostasomes to the extracellular environment. Furthermore, the abilities favouring prostate metastatic tumour cell survival and motility in an otherwise hostile environment are upregulated in prostasomes deriving from prostate cancer cells compared to prostasomes from normal secretory prostate cells.

Studies of laboratory test utilization in Sweden

Researchers involved: Mirja Mindmark and Anders Larsson

The primary objective of the laboratory test utilization project is to increase our knowledge of the use of laboratory tests in Sweden. We have shown that there is a great variability between primary care units in Uppland. We have also shown that it is possible to generate significant changes in the ordering habits of general practitioners by continuous education in a short-time follow up.

Studies of cystatin C and inflammation markers

Researchers involved: Johanna Helmersson-Karlqvist, Mats Flodin, Lars-Olof Hansson and Anders Larsson

Estimation of the glomerular filtration rate (eGFR) is essential for the diagnosis and monitoring of patients with kidney disease and for correct dosage of drugs that are eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine for estimation of eGFR. We have shown that cystatin C estimated GFR has a very good correlation with iohexol estimated GFR both in patients with slight and severe kidney disease. Cystatin C also has a low diurnal variability, which facilitates the use of the marker. Cystatin C is also a promising risk marker for cardiovascular morbidity and mortality and is significantly correlated with HbA1c, diabetes and inflammation in elderly males.