Glutamine and tetrapeptide repeat variations affect the biological activity of different mouse interleukin-2 alleles

Mouse interleukin-2 (IL-2) was thought to be encoded by a single allele. We have recently described N-terminal differences in five IL-2 molecules from nine mouse strains analyzed (Matesanz, F., Alcina, A. and Pellicer, A., Immunogenetics 1993. 38: 300). In this study, we isolated and sequenced the cDNA of three polymorphic IL-2 molecules and constructed two recombinant IL-2 molecules to cover representative structural changes and to address the functional significance of these changes using human and mouse cellular assays in vitro. Apart from punctual codon changes, major differences include an expanding CAG codon (translated into glutamine) and the presence of the tetrapeptide Pro-Thr-Ser-Ser repeated 1, 2, or 3.5 times which is also present once in human IL-2. This tetrapeptide repeat includes an O-glycosylation site. These recombinant IL-2 proteins were expressed at high levels in bacteria and purified by preparative SDS-PAGE with a complete activity recovery. Differences in growth-inducing activity on mouse primary splenocytes were observed in some of them, although no differences were observed in proliferative stimulation of CTLL cells. In human peripheral blood lymphocytes and the T cell line Kit-225, the growth stimulation capacity was inversely dependent on the size of the glutamine stretch and the number of tetrapeptide repeats. These results suggest an evolutionary adaptation of the mouse IL-2/IL-2 receptor system that maintains polyglutamine extensions in the IL-2 molecule. In summary, mouse IL-2 polymorphism results in different bioactivities which may determine susceptibility or resistance to disease.     

Present and future of kidney transplantation

Renal transplant is the treatment of choice for the patient with end stage renal disease. Spain is the country with the highest donation rate (33 ppm). However, at present this figure is stabilized. The development of non-beating heart programmes, living-donor nephrectomy (specially laparoscopic nephrectomy) programmes, and may be xenotransplantation in a non-immediate future could increase the transplantation activity. The knowledge of preservation mechanisms, specially with the use of perfusion machines allows to rescue for transplantation kidneys with a long warm-ischemia time. Furthermore, these machines are useful for analyzing viability markers. The new immunosuppressive drugs: Tacrolimus, Mycophenolate-Mophetil, Rapamycin and monoclonal antibodies against alpha chain of the interleukine-2 receptor (Basoliximab and Dazcizumab) have reduced the incidence of acute rejection in the immediate renal transplant period. However, its effect in the long-term follow-up period is still a matter of controversy. The incidence of tumour in the renal transplant recipient is increased, specially those of lymphoma, skin cancer and Kaposi sarcoma. Periodical exams for detecting the development of tumours are mandatory in this population. Finally, xenotransplantation is an attractive alternative, although immunological, infective and ethical barriers should previously be resolved.     

Lack of association between -384 and 114 IL-2 gene polymorphisms and rheumatoid arthritis

OBJECTIVE: To investigate the association of 2 single nucleotide polymorphisms (SNP) at positions -384 and 114 in the human interleukin 2 (IL-2) gene with susceptibility to and severity of rheumatoid arthritis (RA). METHODS: Genotyping for these IL-2 variants was performed by a polymerase chain reaction restriction fragment length polymorphism method in 174 RA patients and 153 control individuals. RESULTS: No statistically significant differences were observed when the -384 and 114 IL-2 genotype distributions between RA patients and healthy controls were compared. In addition, no association was found between the IL-2 genotypes with any demographic and clinical variables tested. CONCLUSION: Our results provide no evidence for genetic association conferred by the -384 and 114 IL-2 SNP with respect to susceptibility and severity of RA.     

Factors influencing the adaptation of the Spanish Model of organ donation

Spain is the only existing example of a large country (40 million inhabitants) with a continuous increase in cadaveric organ donation for a period of over 10 years, and, in parallel, with an increase in the overall number of solid organ transplantations. A proactive donor detection program performed by well-trained transplant coordinators, the introduction of systematic death audits in the hospitals combined with a positive social atmosphere, adequate management of mass media relations, and adequate economic reimbursement for the hospitals accounted for this success. Some regions of Italy, for example Tuscany, have successfully adapted this approach with excellent results. We can conclude that the "Spanish Model" can be partially or totally adapted to other countries or regions if basic conditions are guaranteed. An adequate and careful study of the local characteristics that influence organ donation directly or incirectly should be carried out before planning any specific action to improve organ donor rates.