<p> Between 8% and 10% of patients diagnosed with common variable immunodeficiency (CVID) have known mutations in the gene coding for transmembrane activator and calcium-modulating ligand interactor (TACI). Family members of CVID patients carrying the same mutations, but lacking clinical symptoms of CVID, have left the role of TACI in hypogammaglobulinemia unclear. There are two described isoforms of TACI observed at the mRNA and protein levels in humans, a long and a short form, identical save for the exclusion of the second cysteine-rich domain in the short form. The aim of this study was to determine which isoforms contain mutations in a subset of patients and their healthy relatives all known to carry at least one heterozygous mutation in TACI at the genomic level. All patients and healthy relatives carried TACI mutations within their long isoforms. However, in the cohort examined, mutations in the short isoform were only present in CVID patients and one healthy relative. These results may implicate the short isoform of TACI in CVID progression. Our lab has observed that the short isoform induces plasma cell differentiation more efficiently than the long, so this data also supports a more active role for the short isoform in B cell immunology. Mutation localization within additional CVID patients and mutation carrying relatives must be studied to determine if this trend is still significant.</p>
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:1537184 |
| Date | 07 June 2013 |
| Creators | Barrette, Anne Marie |
| Publisher | Icahn School of Medicine at Mount Sinai |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
Page generated in 0.002 seconds