Mario Plebani

Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium.

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: ru2009=u20090.32, Pu2009<u2009.001; sPGII: ru2009=u20090.56, Pu2009<u2009.001) and antrum (sPGI: ru2009=u20090.41, Pu2009<u2009.001; sPGII: ru2009=u20090.43, Pu2009<u2009.001) as well as with chronic inflammation (sPGI: ru2009=u20090.26, Pu2009<u2009.001; sPGII: ru2009=u20090.49, P < .001) and activity (sPGI: ru2009=u20090.38, Pu2009<u2009.001; sPGII: ru2009=u20090.50, Pu2009<u2009.001) in the antrum. Only sPGII was correlated with chronic inflammation (ru2009=u20090.44, Pu2009<u2009.001) and activity (ru2009=u20090.40, Pu2009<u2009.001) in the corpus. SPGI was inversely correlated with atrophy (ru2009=u2009–0.33, Pu2009<u2009.001) and intestinal metaplasia (ru2009=u2009–0.37, Pu2009<u2009.001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.

Serum Elastase 1 and Immunoreactive Trypsin in Chronic Pancreatic Disease: Is There Any Relationship with Trypsin Inhibitors?

In order to investigate modifications of serum levels of elastase 1, immunoreactive trypsin, alpha 1-antitrypsin and alpha 2-macroglobulin in chronic pancreatic disease, and to speculate on the possible relationships among these parameters, the enzymes and inhibitors were assayed in the sera of 33 control subjects, 34 pancreatic cancer, 28 chronic pancreatitis and 36 extra-pancreatic diseases. An increase of elastase 1, alpha 1-antitrypsin and alpha 2-macroglobulin was detected in pancreatic cancer, chronic pancreatitis and extra-pancreatic diseases; no changes were found for serum immunoreactive trypsin. Multiple regression analyses showed that only 7% of elastase 1 was explained by inhibitors with alpha 1-antitrypsin playing a major role. Inhibitors did not influence immunoreactive trypsin. Our data indicate that the variations of the serum levels of proteases and antiproteases in chronic pancreatic disease are probably independent of each other.

Chapter 3.6 – Biomarker Panels and Multiple Readouts

Powerful new technologies in diagnostic laboratory testing exist to offer unprecedented prospects for translating early and accurate diagnoses of human disorders into improvements in clinical care (Plebani and Laposata, 2006). High-throughput technologies, such as mass spectrometry and microarrays, allow measurements of proteins and RNA/DNA to be carried out in large numbers. The enormous amount of data produced during genetics and proteomics analysis, coupled with the inherent variation in the instrumentation used as well as the biological variation of the subjects, requires the utilization of sound experimental design, proper calibration of instruments, and appropriate biostatistics/bioinformatics methods in order to generate good-quality data by which valid conclusions could be drawn. In particular, some strategies have to be used and applied to assure the appropriate interpretation and utilization of such laboratory information, given the complexity of large volumes of data and numbers, which potentially could create confusion in practicing physicians. While the field is complex, presenting several areas of research and development, we would like to focus on some relevant issues:

Growth in Celiac Disease: Impact on Physical and Compartmental Growth

Typical, atypical, silent, and latent clinical forms of celiac disease, an immune mediated enteropathy triggered by gluten intake, have been described in literature. In overt, atypical, and silent forms of the disease, intestinal villous atrophy is detected, whereas in the latent forms, with a normal villous architecture, the biochemical indexes of disease (i.e., anti-transglutaminase antibodies, tTG) are altered. Villous atrophy causes nutrient malabsorption, which can selectively affect either divalent cations, such as iron, or the entire spectrum of nutrients. Although celiac disease occurs in children in the majority of cases, and can have a significant impact on their overall growth, its frequency in adults has reportedly increased; in this age category, celiac disease mainly causes the selective malabsorption of nutrients, with consequent selective growth deficiencies, including iron deficiency anemia and osteoporosis. It is therefore of utmost importance at diagnosis, which is based on biochemical (tTG) and histological (duodenal histology with evidence of crypt hyperplasia and various degrees of villous atrophy) findings, to make an overall (weight and height) and selective (e.g., iron, calcium, and vitamins) evaluation of growth deficiencies. While follow-up for patients with uncomplicated celiac disease on a gluten-free diet does not call for a histological evaluation, it should include tTG to assess diet compliance and laboratory tests for nutritional status assessment (i.e., red blood cell count, iron, ferritin, calcium, and cholesterol).