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An immunologicalbiomarker to predictMTX response in earlyRA Frédérique PonchelVincent GoëbRekha Parmar2013 год

An immunological biomarker to predict MTX response in early RA
статья из журнала

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Аннотация:

Objectives

The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis and appropriate therapeutic intervention. RA is associated with dysregulation of T-cell subsets (naïve, regulatory (Treg) and inflammation-related cells (IRC)) early in the disease. Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission with early treatment in RA.

Methods

T-cell subsets were quantified in 108 drug-naïve, early RA patients commencing methotrexate (MTX) or MTX+antitumor necrosis factor (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28<2.6). A pilot study used frozen cells (38 patients and 35 HCs, see online supplementary material) and was validated with fresh blood (70 patients and 70 HCs).

Results

Immune dysregulation in early RA was confirmed with an association between age and reduced naïve cells compared with HCs (p=0.006), a lower age-adjusted Treg and higher IRC frequency (p=0.001). Anticitrullinated peptide antibody (ACPA) positivity was associated with lower naïve (p=0.031) and Treg frequencies (p=0.039). In 50 patients treated with MTX, ACPA/age-adjusted analysis demonstrated that higher naïve cell frequency (relative to HC) was associated with remission (OR 5.90 (1.66 to 20.98), p=0.006, sensitivity/specificity 62%/79%, Positive Predictive Value (PPV)/Negative Predictive Value (NPV) 66%/76%). Remission with MTX+anti-TNF (n=20) was not found to be associated with naïve cell frequency, and for patients with reduced naïve cells the remission rate increased from 24% (MTX) to 42% (MTX+anti-TNF).

Conclusions

Baseline T-cell subset analysis has a value in predicting early RA remission with first therapy with MTX. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and help select the most appropriate therapy at disease presentation.
Год издания: 2013
Авторы: Frédérique Ponchel, Vincent Goëb, Rekha Parmar, Yasser M. El‐Sherbiny, Marjorie Boissinot, Jehan J. El‐Jawhari, Agata Burska, Edward M Vital, Stephanie Harrison, Philip G. Conaghan, E. Hensor, Paul Emery
Издательство: BMJ
Источник: Annals of the Rheumatic Diseases
Ключевые слова: Rheumatoid Arthritis Research and Therapies, Autoimmune and Inflammatory Disorders Research, Viral Infections and Immunology Research
Другие ссылки: Annals of the Rheumatic Diseases (HTML)
PubMed (HTML)