Blood autoantibody,cytokine profiles and TNF's | Arthritis Information

 

Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis:

Introduction

Anti-tumor necrosis factor (anti-TNF) therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers.

Methods

Here we present a multi-step proteomics approach using arthritis antigen arrays, a multiplex cytokine assay, and conventional ELISA, with the objective to identify a biomarker signature in three ethnically diverse cohorts of RA patients treated with the anti-TNF therapy etanercept.

Results

We identified a 24-biomarker signature that enabled prediction of a positive clinical response to etanercept in all three cohorts (positive predictive values (PPV) 58 to 72%; negative predictive value (NPV) 63 to 78%).

Conclusions

We identified a multi-parameter protein biomarker that enables pretreatment classification and prediction of etanercept responders, and tested this biomarker using three independent cohorts of RA patients. Although further validation in prospective and larger cohorts is needed, our observations demonstrate that multiplex characterization of autoantibodies and cytokines provides clinical utility for predicting response to the anti-TNF therapy etanercept in RA patients.

 

http://arthritis-research.com/content/11/3/R76

Testing for efficacy would sure save some trouble (and maybe some heart ache) in the long run.  I suppose this all goes to individualized testing and treatment... something we have talked about before. 

Great find!  Thanks.

This sounds like the beginning or at least a part of individualized treatment.....I'm waiting very impatiently, hopefully it will be here in my lifetime.  Lindy 

Yes, a beginning; and exciting one for me. From the PDF presentation of the study...
http://arthritis-research.com/content/pdf/ar2706.pdf
[quote]
Newly described markers include
several native and non-filaggrin-derived citrullinated antigen epitopes as presented in
Table 2. Our data also demonstrate that cytokines alone are likely insufficient to
accurately predict treatment responses in a general population, and combinations of
autoantibodies and cytokines provide increased predictive utility across ethnically diverse
and clinically heterogeneous RA populations. Additional markers (imaging, genetic,
clinical) may eventually have to be incorporated in a definitive panel of biomarkers [31],
for the future development of a prediction score that could be applied for reliable patient
stratification.

Although this study utilizes samples from three cohorts of patients, important
limitations remain: (i) the number of samples per cohorts is relatively small; (ii) a number
of samples demonstrated undetectable serum levels of cytokines; (iii) the quantification
of response to therapy in RA is intrinsically inaccurate since response classification is
based on short term follow-up; (iv) our data may underestimate the predictive value of
these biomarkers for predicting response to anti-TNF therapy since concomitant DMARD
medication in the three cohorts was not uniform. Moreover, a full validation in
independent cohorts of the identified markers is not presented in this paper. Because of
the small sample numbers in the individual cohorts and the fact that the experiments were
performed over a 3-year period, this study represents a discovery and testing study. The
training was performed on the full dataset, and the resulting panel of markers were tested
in the three individual cohorts. These limitations indicate the need for larger validation
studies and prospective serum proteome studies in cohorts where longer-term response
outcomes are available.[/quote]

...discovery and testing...a beginning!

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