Meta-analysis: diagnostic accuracy of antibody against peptidylarginine deiminase 4 by ELISA for rheumatoid arthritis

Abstract

The antibody against peptidylarginine deiminase (PAD) 4 is a biomarker that might be helpful in the diagnosis of rheumatoid arthritis (RA). We aim to estimate the diagnostic value of anti-PAD4 antibody for RA by meta-analysis. We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus for studies published in any languages in March 1, 2017 that evaluated the diagnostic accuracy of the anti-PAD4 antibody for the diagnosis of RA. The articles that detected the anti-PAD4 antibody by enzyme-linked immunosorbent assay (ELISA) and used healthy donors or patients without arthritis or arthralgia as controls were included for meta-analysis. The articles were assessed by Quality Assessment of Diagnostic Accuracy Studies tool. A bivariate mixed-effects model was used to summarize the diagnostic indexes from eight eligible studies. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-PAD4 antibody were 38% (95% CI 30.0-46.0%), 96% (95% CI 93.0-98.0%), 8.96 (95% CI 5.00-16.05), and 0.65 (95% CI 0.57-0.74), respectively. The summary diagnostic odds ratios were 13.74 (95% CI 7.23-26.09), and the area under the summary receiver operator characteristic curve was 86% (95% CI 83-89%). Anti-PAD4 antibody detected by ELISA shows a high value in the diagnosis of RA with high specificity, but relatively low sensitivity.

Autoantibodies in Rheumatoid Arthritis – Laboratory and Clinical Perspectives

“…Antibodies against peptidyl arginine deiminase-4 (PAD-4), an enzyme responsible for citrullination, was originally detected in 36-42% or RA patients with high specificity (51), and gained interest as anti-PAD-4 could inhibit citrullination of fibrinogen (52). A meta-analysis has suggested rather low diagnostic sensitivity but high specificity for anti-PAD-4 (53). Antibodies against glucose-6-phosphate isomerase (anti-GPI), distinctively pathogenic in the K/BxN T cell receptor transgenic mouse arthritis model, were first described in 64% of RA patients but not in controls (54).…”

The challenges of early diagnosis and therapeutic prediction in rheumatoid arthritis

“…Triple positivity of ACPA, RF and anti‐CarP antibodies is highly specific for very early identification of individuals at risk of developing RA . Meta‐analysis confirms that anti‐peptidylarginine deiminase (PAD) 4 antibodies are specific biomarkers in RA patients . Serum 14‐3‐3η protein has been considered as a novel biomarker for RA .…”

New laboratory biomarkers of rheumatoid arthritis

“…Опосредованное ПАД-4 цитруллинирование белков участвует в формировании нейтрофильных внеклеточных ловушек (NETоз, Neutrophil Extracellular Trap), индуцирует синтез провоспалительных цитокинов, дифференцировку остеокластов и костную резорбцию [8, [45][46][47][48]. По данным метаанализа (8 исследований), диагностическая чувствительность анти-ПАД4 составила 38%, специфичность -96%, при разбросе значений от 23,5 до 60,0% и от 82,4 до 100,0% соответственно [49]. Следует подчеркнуть, что, как и другие аутоантитела, анти-ПАД4 могут выявляться до клинической манифестации РА.…”