Respiratory and Systemic Diseases
Immunology
Ricardo Pujol Borrell
Researchers
Mónica Martínez Gallo, Isabel Caragol Urgellés, Roger Colobran Oriol, Mireia Gimenez Barcons , Manuel Hernández González , Ana María Marín Sánchez, Daniel Alvarez de la Sierra, Clara Franco Jarava, Laura Viñas Giménez
SUMMARY
Down syndrome individuals develop autoimmunity in general and thyroid autoimmunity in particular. The transcription factor AIRE regulates the predisposition to autoimmunity and is coded in chromosome 21, of which Down Syndrome (DS) individuals carry three copies instead of two. AIRE is almost exclusively expressed in the thymus. Paradoxically, but not uniquely, AIRE expression has been found diminished in the thymus of DS. We have found the link between these observations by demonstrating that the reduction of AIRE expression disturbs the settings of central tolerance to tissue-restricted antigens such as those expressed in endocrine glands. This finding was supported by showing that the subjects who had lower thyroglobulin levels in the thymus were those who more often developed hypothyroidism. This work was made possible by the thymus biobank of the Vall d’Hebron University Hospital and the help of the heart surgery team.
PUBLICATIONS
- Colobran R, Pujol-Borrell R, Hernández-González M, Guilarte M. A novel splice site mutation in the SERPING1 gene leads to haploinsufficiency by complete degradation of the mutant allele mRNA in a case of familial hereditary angioedema. J Clin Immunol. 2014 Jul;34(5):521-3. doi: 10.1007/s10875-014-0042-3. Epub 2014 Apr 24. PubMed PMID: 24760113.
- Colobran R, Lois S, de la Cruz X, Pujol-Borrell R, Hernández-González M, Guilarte M. Identification and characterization of a novel splice site mutation in the SERPING1 gene in a family with hereditary angioedema. Clin Immunol. 2014 Feb;150(2):143-8. doi: 10.1016/j.clim.2013.11.013. Epub 2013 Dec 4. PubMed PMID: 24412907.
- Giménez-Barcons M, Casteràs A, Armengol Mdel P, Porta E, Correa PA, Marín A, Pujol-Borrell R, Colobran R. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens. J Immunol. 2014 Oct 15;193(8):3872-9. doi: 10.4049/jimmunol.1400223. Epub 2014 Sep 12. PubMed PMID: 25217160.
- Alsina L, Colobran R, de Sevilla MF, Català A, Viñas L, Ricart S, Plaza AM, Lois S, Juan M, Pujol-Borrell R, Martinez-Gallo M. Novel and atypical splicing mutation in a compound heterozygous UNC13D defect presenting in Familial Hemophagocytic Lymphohistiocytosis triggered by EBV infection. Clin Immunol. 2014 Aug;153(2):292-7. doi: 10.1016/j.clim.2014.04.019. Epub 2014 May 10. PubMed PMID: 24825797.
- Moreso F, Torres IB, Martínez-Gallo M, Benlloch S, Cantarell C, Perelló M, Jimeno J, Pujol-Borrell R, Seron D. Gene expression signature of tolerance and lymphocyte subsets in stable renal transplants: results of a cross-sectional study. Transpl Immunol. 2014 Jun;31(1):11-6. doi: 10.1016/j.trim.2014.04.008. Epub 2014 May 5. PubMed PMID: 24810779.
MAIN RESEARCH PROJECTS
View- Estudio de la inmunidad mediada por células en el proceso diagnóstico de los pacientes pediátricos con sospecha de inmunodeficiencia combinada (IDC)
PI: Martínez Gallo, Mónica
Funding agency: Fondo de Investigación Sanitaria
Reference: PI11/01086 - Análisis de inmunotolerancia en la enfermedad de Graves y otras enfermedades autoinmunes (diabetes y esclerosis múltiple)
PI: Pujol Borrell, Ricardo
Funding agency: Fondo de Investigación Sanitaria
Reference: PI11/02479 - European Network for Translational Immunology Research and Education (ENTIRE): From Immunomonitoring to Personalized Immunotherapy
PI: Pujol Borrell, Ricardo
Funding agency: European Commission