Gene expression profile in the salivary glands of primary Sjögren's syndrome patients before and after treatment with rituximab.
OBJECTIVE
Primary Sjögren's syndrome (SS) is a complex disorder, in part due to B cell abnormalities. Although anti-B cell therapy is promising in primary SS, no treatment has yet been demonstrated to modify the disease course. This open-label study was undertaken to evaluate the efficacy of rituximab in primary SS and to investigate whether expression of specific genes is associated with efficacy of this treatment.


METHODS
Fifteen patients with primary SS were treated in an open-label trial. Salivary gland biopsy specimens were obtained, and total RNA was extracted and amplified. Microarray analysis with the Affymetrix Human Genome U133 Plus 2.0 Array was used to analyze >54,000 transcripts, and potential pathways were identified.


RESULTS
With gene expression data obtained before treatment, patients could be correctly classified in terms of whether they would be responders or nonresponders to rituximab. Gene pathway analysis demonstrated that the B cell signaling pathway was the most profoundly differentially expressed before treatment in the responders compared with nonresponders. Subclassification of patients based on the level of infiltration also demonstrated differential expression of genes belonging to the interferon (IFN) pathway between responders and nonresponders. Furthermore, unsupervised analysis based on gene expression modification before and after treatment allowed identification of 8 genes that were differentially expressed between responders and nonresponders, with the difference remaining significant after Bonferroni correction.


CONCLUSIONS
Our results demonstrate the ability to elaborate a set of genes predictive of rituximab efficacy and highlight the importance of studying the differential expression of B cell and IFN pathway signaling molecules in relation to the response to anti-CD20 treatment. A randomized controlled study is currently ongoing to confirm these results.
Devauchelle-Pensec
Valérie
V
Hôpital de la Cavale Blanche, Centre Hospitalier Universitaire Brest, and Hôpital Morvan, Brest, France. valerie.devauchelle-pensec@chu-brest.fr
Cagnard
Nicolas
N
Pers
Jacques-Olivier
JO
Youinou
Pierre
P
Saraux
Alain
A
Chiocchia
Gilles
G
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000069283:Rituximab; D012469:Salivary Glands / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D012333:RNA, Messenger; D000069283:Rituximab