Table 2 Overview of gene expression analysis obtained from small proof-of-concept studies using synovial biopsies in RA

Infliximab

Baseline

Differential baseline gene expression in responders and non-responders. Overexpression of genes involved in T-cell mediated immunity, cell surface receptor mediated signal transduction, major histocompatibility complex II (MHCII)-mediated immunity, cell adhesion, cytokine and chemokine mediated signalling, cell adhesion mediated signalling, signal transduction, and macrophage-mediated immunity identified in responders.

[88]

Infliximab

9 weeks

Unique baseline transcriptome in all patients. 279 differentially expressed genes between good responders and non-responders. Significant change in expression of 115 genes in the good responding group involved in immune response, cell communication, signal transduction and chemotaxis.

[56]

Adalimumab

12 weeks

Deregulated baseline expression of 439 genes involved in cell cycle and immune responses in good vs. poor responders. Differential expression of 632 genes enrolled in cell division, signal transduction, antigen processing/presentation, T-cell activation, and apoptosis upon adalimumab treatment in a group of good responders.

[73]

Rituximab

12 weeks

Deregulated baseline expression of 2458 genes involved in immunoglobulin clusters, antigen processing and presentation via MHCII in non-responders vs. responders. Treatment with rituximab resulted in downregulation of 220 genes enriched in immunoglobulin clusters, chemotaxis, leukocyte activation and immune responses; upregulation of 329 genes involved in cell development and wound healing.

[51]

Rituximab

12 weeks

21 months

Baseline differential expression of genes involved in T cell and macrophage function, remodelling and interferon-α biology between non-responders vs. responders at months 3, 9 and 21. Downregulation of CD20 at 3 and 12 months, differential expression of multiple genes involved in B and T cell biology at 21 months (e.g. CD27, CD38, CD8, CD52, CTLA4, CD122, FOXP3, IL-6, IL-12, IL-13, IL-17RA, IL-23a, IL-32, CCL5, MMP3, FASLG)

[89]

Tocilizumab

12 weeks

Downregulation of 3413 genes involved in cytokine/chemokine pathways and T cell activation, upregulation of 3270 genes involved in healing process. Downregulation of genes involved in induction of apoptosis and myeloid cell differentiation, and upregulation of genes involved in regulation of Ras protein signal transduction and ubiquitin-dependent protein catabolic processes observed in responders achieving remission at 6 months.

[50]

Methotrexate

12 weeks

Downregulation of 586 genes enriched in T cell activation and immune response pathways, upregulation of 610 genes. Downregulation of genes enrolled in cell division in responders achieving remission at 6 months.

[50]