Selected Articles April 2014
Sulfatide does not modulate the course of type 1 diabetes in NOD mice
Administration of Sulfatide to Ameliorate Type I Diabetes in Non-Obese Diabetic Mice
S. Rhost, L. Löfbom, J.-E. Månsson, A. Lehuen, M. Blomqvist and S. L. Cardell
In this paper from Susanna Cardell´s lab in Gothenburg it is shown that the course of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice cannot be modulated by the glycosphingolipid sulfatide, which is something that has been published earlier (Lakshmimathy Subramanian et al, PLOS ONE 2012).
The study was initiated to investigate immune reactivity to sulfatide in NOD mice and the ability of the sulfatide treatment to modulate T1D development. It has been shown previously that human T1D patients, but not patients with type 2 diabetes nor healthy individuals have autoantibodies against sulfatide in serum, suggesting that sulfatide induces an immune response in the natural course of T1D in humans. In the present study, sulfatide was investigated as an autoantigen and a modulator of autoimmune disease in NOD mice. The results show that some NOD mice develop autoantibodies towards sulfatide with age, however it did not correlate with T1D progression. These data are thus in contrast to what has been described for human patients with T1D.
– This suggests that the murine model for T1D, the NOD mouse model may possess differences in the immune response towards sulfatide compare to humans in relation to the T1D development, says Sara Rhost, first author of the study.
Sara Rhost is a former PhD student in the research group of Susanna Cardell. She is now a postdoc at Monash University in Melbourne, Australia, and she thinks that working together with highly motivated and skilled collaborators was the most rewarding during the work that led to this paper.
Impaired classical complement activity in extreme preterm neonates
Complement Profile in Neonates of Different Gestational Ages
A. S. Grumach, M. E. Ceccon, R. Rutz, A. Fertig and M. Kirschfink
In a study by Anete Grumach and co-workers the relative immaturity of the complement system and its regulation in premature infants is demonstrated.
The proteins of the complement system are synthesized early in foetal life, although with a relative deficiency of most of the complement proteins in comparison with adult levels.
This study was not restricted to evaluate a specific population but evaluates protein regulators of the complement system not studied by others before.
Complement activity, levels of mannan-binding lectin, complement regulators and C3a as a marker of complement activation were assessed in three groups of healthy new-borns:
1) prematures (≤ 34 weeks)
2) late prematures (>34 – <37 weeks)
3) term neonates (≥ 37 weeks)
It was found that functional impairment of the classical pathway activity existed in almost all samples, with higher levels in term babies. Cord blood levels of quantitative and functional C1 inhibitor and of factors H and I progressively increased with gestational age.
– The findings may reflect not only the immaturity of complement system but it could suggest an additional factor predisposing to infections, says Anete Grumach who, together with Dr Michael Kirschfink, was responsible for planning the project.
The results showed that extreme preterm neonates lack total classical complement activity. Although the low titres of classical and alternative pathway functions are considered as risk factors for infections, an impaired regulation may pose an additional risk for uncontrolled complement-mediated inflammatory tissue destruction.
– The sample collection was extremely hard considering the gestational age, says Anete Grumach.
For me as a paediatrician, the evaluation of the results was very interesting and also the comparison with other studies.