HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Microarrays reveal distinct gene signatures in the thymus of seropositive and seronegative myasthenia gravis patients and the role of CC chemokine ligand 21 in thymic hyperplasia.

Abstract
Myasthenia gravis (MG) is an autoimmune disease mainly caused by antiacetylcholine receptor autoantibodies (seropositive (SP) disease) or by Abs against unknown autoantigenic target(s) (seronegative (SN) disease). Thymectomy is usually beneficial although thymic hyperplasia with ectopic germinal centers is mainly observed in SP MG. To understand the role of thymus in the disease process, we compared the thymic transcriptome of non-MG adults to those of SP patients with a low or high degree of hyperplasia or SN patients. Surprisingly, an overexpression of MHC class II, Ig, and B cell marker genes is observed in SP but also SN MG patients. Moreover, we demonstrate an overexpression of CXCL13 in all MG thymuses leading probably to the generalized B cell infiltration. However, we find different chemotactic properties for MG subgroups and, especially, a specific overexpression of CCL21 in hyperplastic thymuses triggering most likely ectopic germinal center development. Besides, SN patients present a peculiar signature with an abnormal expression of genes involved in muscle development and synaptic transmission, but also genes implicated in host response, suggesting that viral infection might be related to SN MG. Altogether, these results underline differential pathogenic mechanisms in the thymus of SP and SN MG and propose new research areas.
AuthorsRozen Le Panse, Géraldine Cizeron-Clairac, Jacky Bismuth, Sonia Berrih-Aknin
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 11 Pg. 7868-79 (Dec 01 2006) ISSN: 0022-1767 [Print] United States
PMID17114458 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantibodies
  • CCL21 protein, human
  • Chemokine CCL21
  • Chemokines, CC
Topics
  • Adult
  • Autoantibodies (blood)
  • Chemokine CCL21
  • Chemokines, CC (metabolism)
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Male
  • Myasthenia Gravis (blood, genetics, immunology)
  • Oligonucleotide Array Sequence Analysis
  • Thymus Gland (physiology)
  • Thymus Hyperplasia (blood, genetics, immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: