Back in 1980 Inge Dale and Magne K. Fagerhol immunized rabbits with fractionated samples of leukocytes; among many antibodies one differed markedly from the others, forming distinct immunoprecipitates in gel containing Ca++-ions. In 1983 the study “Purification and Partial Characterization of a Highly Immunogenic Human Leucocyte Protein, the L1 Antigen” was published. Further investigations showed that each molecule binds 6 Ca-atoms, and as purified protein also inhibits the growth of certain bacteria in vitro, we renamed the protein “Calprotectin”. Quantitative methods for assessment of calprotectin in blood and tissues were established in 1984, including an ELISA, and during the eighties immunohistochemical studies were performed by Inge Dale, showing that the protein is abundantly found in neutrophil granulocytes, counting for 60 % of the proteins in the cytoplasm. Blood monocytes, like tissue macrophages, which are monocytes that have passed through the walls of vessels and migrated into the tissues, are also calprotectin positive. In addition, squamous epithelium of internal organs (esophaguis, mouth, vagina), and the cells of squamous cell carcinoma are also calprotectin positive. In 1991 Inge Dale did his doctoral thesis on these studies. During the first half of the nineties 3 Scandinavian ph.d.’s were published; all based on the original quantitative technology, using our purified calprotectin and polyclonal antibodies.
Calprotectin is an abundant component of inflammatory cells; quantitative measurement of the protein is often helpful in the diagnosos and treatment of inflammatory and malignant conditions. Neutrophils, which are vulnerable and short-lived cells, are produced in the bone marrow and mobilized to the blood in large amounts in inflammatory conditions, migrating into inflamed tissue where active enzymes and also calprotectin are released from the cells. In IBD neutrophils migrate through the wall of the intestine and calprotectin is consequently found in increased amounts in stools; feces concentrations more than hundred times the upper cut off value can be found in IBD. Calpro AS was established in 1993, and based on the technology of Calpro the first commercial ELISA kit, Nycomed ELISA, for determination of calprotectin in faeces was launched in 1994. A patented buffer for extraction of calprotectin from feces, which had been developed by Calpro, was included in the test kit. In 2000 an improved assay was developed by Tøn et al. Whereas the initial cut off value for fecal calprotectin between normal and patients with organic bowel disease was 10 mg/kg, it was now increased to 50 mg/kg, which is still recommended for the Calpro kits. Samples with high calprotectin values were increased to a slightly higher degree than low calprotectin samples, thus improving the separation between high and low calprotectin levels.
In the 20th century there was no commercial test kit available except Nycomed ELISA based on Calpro technology, but after standardized extraction methods had been developed and some gastroenterologists described faecal calprotectin as a promising noninvasive marker to differentiate IBD from IBS, the interest “exploded” around 2000. Up to now more than 2000 studies on calprotectin are published in peer review journals. Several issues regarding the use of fecal calprotectin testing in clinical medicine are discussed, included methodological and economic aspects.
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Li XG, Lv YM, Gu F, Yang XL., Department of Gastroenterology, Peking University Third May 9, 2015
The PhiCal Test has now been approved by the FDA for clinical use in the USA October 1, 2014
Please see the Calpro press release regarding MDS agreement for delivery of e-health technology CalproSmart:Norsk | English October 13, 2016