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Update on Targets of Biologic Therapies for Rheumatoid Arthritis.

ABSTRACT: With the advent of biological therapies, considerable progress has been made in the treatment of rheumatoid arthritis (RA). These revolutionary therapies owe their origin to the role that cytokines play in the pathophysiology of the disease and are best exemplified by the wide use of tumor necrosis factor (TNF) blockade. The identification of additional pro-inflammatory factors and an understanding of their effector function now offer major possibilities for the generation of additional novel biological therapeutics to address unmet clinical needs. Such interventions will ideally fulfill several of the following criteria: control of inflammation, modulation of underlying immune dysfunction by promoting the reestablishment of immune tolerance, protection of targeted tissues such as bone and cartilage, and preservation of host immune capability to avoid profound immune suppression and amelioration of co-morbidity associated with underlying RA. The identification and characterization of the intracellular signaling pathways, in particular, the mitogen-activated protein kinase pathway, the nuclear factor-?B pathway and the cross-talk between these pathways offer several potential therapeutic opportunities. This review will provide an update on cytokine activities and signal transduction pathways that represent, in our opinion, optimal utility as future therapeutic targets.

SUBMITTER: Rasheed Z

PROVIDER: S-EPMC2822346 | biostudies-other | 2008 Nov

REPOSITORIES: biostudies-other

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Update on Targets of Biologic Therapies for Rheumatoid Arthritis.

Rasheed Zafar Z Haqqi Tariq M TM

Current rheumatology reviews 20081101 4

With the advent of biological therapies, considerable progress has been made in the treatment of rheumatoid arthritis (RA). These revolutionary therapies owe their origin to the role that cytokines play in the pathophysiology of the disease and are best exemplified by the wide use of tumor necrosis factor (TNF) blockade. The identification of additional pro-inflammatory factors and an understanding of their effector function now offer major possibilities for the generation of additional novel bi ...[more]

PMID: 20165551

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Project description:Rheumatoid arthritis (RA) is a systematic autoimmune disease, predominantly causing chronic polyarticular inflammation and joint injury of patients. For the treatment of RA, biologic disease-modifying antirheumatic drugs (bDMARDs) have been used to reduce inflammation and to interfere with disease progression through targeting and mediating the immune system. Although the therapeutic effects of bDMARDs in RA patients have been widely reported, whether these drugs also play important roles in T-cell repertoire status is still unclear. We therefore designed the study to identify the role of T-cell repertoire profiles in RA patients with different types of bDMARD treatments. A high-throughput sequencing approach was applied to profile the T-cell receptor beta chain (TCRB) repertoire of circulating T lymphocytes in eight patients given adalimumab (anti-TNF-α) with/without the following use of either rituximab (anti-CD20) or tocilizumab (anti-IL6R). We subsequently analyzed discrepancies in the clonal diversity and CDR3 length distribution as well as usages of the V and J genes of TCRB repertoire and interrogated the association between repertoire diversity and disease activities followed by the treatment of bDMARDs in these RA patients. All groups of patients showed well-controlled DAS28 scores (<2.6) after different treatment regimens of drugs and displayed no significant statistical differences in repertoire diversity, distribution of CDR3 lengths, and usage of V and J genes of TCRB. Nonetheless, a trend between overall TCRB repertoire diversity and disease activity scores in all bDMARD-treated RA patients was observed. Additionally, age was found to be associated with repertoire diversity in RA patients treated with bDMARDs. Through the profiling of the TCR repertoire in RA patients receiving different biologic medications, our study indicated an inverse tendency between TCR repertoire diversity and disease activity after biologic treatment in RA patients.

Dataset Information

Update on Targets of Biologic Therapies for Rheumatoid Arthritis.

Publications

Update on Targets of Biologic Therapies for Rheumatoid Arthritis.

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