Recommended Conferences

Cancer-Treatment and Therapeutics

New York, USA
Related Subjects
 

Adalimumab regulates intracellular TNFa production in patients with rheumatoid arthritis

Author(s): Zamora-Atenza C, Diaz-Torne C, Geli C, Diaz-Lopez C, Ortiz MA, et al.

Abstract

Introduction

Adalimumab is a fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients.

Methods

We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors.

Results

Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment.

Conclusions

Our findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.

Similar Articles

The burden of skin diseases

Author(s): Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, et al.

The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions

Author(s): Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP et al.

Economic Burden of Psoriasis in the United States

Author(s): Brezinski EA, Dhillon JS, Armstrong AW

Maintaining skin integrity in the aged: A systematic review

Author(s): Kottner J, Lichterfeld A, Blume-Peytavi U

Nuclear receptors and lipid physiology: opening the X-files

Author(s): Chawla A, Repa R, Evans M, Mangelsord DJ

The pleiotropic actions of vitamin D

Author(s): Lin R, White JH

Vitamin D and the anti-viral state

Author(s): Jeremy A. Beard A, Striker A

Therapeutic implications of the TLR and VDR partnership

Author(s): Liu PT, Krutzik SR, Modlin RL

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D dependent mechanism

Author(s): Robert SJA, Dorschner, Coda AB, Büchau AS, Liu PT, et al.

2016

Author(s): Arantes EL, Dragano N, Ramalho A, Vitorino D, de-Souza GF, et al

A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice

Author(s): Da Young Oh, Walenta E, Akiyama TE, Lagakos WS, Lackey D, et al.

Vitamin D receptor is essential for normal keratinocyte stem cell function

Author(s): Cianferotti L, Cox M, Skorija K, Demay MB

UV photoprotection by combination topical antioxidants vitamin C and vitamin E

Author(s): Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, et al.

CAM use in dermatology

Author(s): Barbosa NS, Kalaaji AN

The role of vitamin C in pushing back the boundaries of skin aging: an ultrasonographic approach

Author(s): Crisan D, Roman I, Crisan M, Scharffetter-Kochanek K, Badea R

MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search

Author(s): Noa Rappaport, Twik M, Plaschkes I, Nudel R, Iny Stein T, Levitt J, et al.

The burden of skin diseases

Author(s): Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, et al.

The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions

Author(s): Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP et al.

Economic Burden of Psoriasis in the United States

Author(s): Brezinski EA, Dhillon JS, Armstrong AW

Maintaining skin integrity in the aged: A systematic review

Author(s): Kottner J, Lichterfeld A, Blume-Peytavi U

Adalimumab regulates intracellular TNFa production in patients with rheumatoid arthritis

Author(s): Zamora-Atenza C, Diaz-Torne C, Geli C, Diaz-Lopez C, Ortiz MA, et al.

Nuclear receptors and lipid physiology: opening the X-files

Author(s): Chawla A, Repa R, Evans M, Mangelsord DJ

The pleiotropic actions of vitamin D

Author(s): Lin R, White JH

Vitamin D and the anti-viral state

Author(s): Jeremy A. Beard A, Striker A

Therapeutic implications of the TLR and VDR partnership

Author(s): Liu PT, Krutzik SR, Modlin RL

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D dependent mechanism

Author(s): Robert SJA, Dorschner, Coda AB, Büchau AS, Liu PT, et al.

2016

Author(s): Arantes EL, Dragano N, Ramalho A, Vitorino D, de-Souza GF, et al

A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice

Author(s): Da Young Oh, Walenta E, Akiyama TE, Lagakos WS, Lackey D, et al.

Vitamin D receptor is essential for normal keratinocyte stem cell function

Author(s): Cianferotti L, Cox M, Skorija K, Demay MB

UV photoprotection by combination topical antioxidants vitamin C and vitamin E

Author(s): Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, et al.

CAM use in dermatology

Author(s): Barbosa NS, Kalaaji AN

The role of vitamin C in pushing back the boundaries of skin aging: an ultrasonographic approach

Author(s): Crisan D, Roman I, Crisan M, Scharffetter-Kochanek K, Badea R