Evaluation of Automated Assays for Measuring Serum Hyaluronic Acid: For the Diagnosis of Rheumatoid Arthritis

Mi-Soon Han; Yongjung Park; Hyon-Suk Kim

doi:10.3343/lmo.2014.4.2.98

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Han, Park, and Kim: Evaluation of Automated Assays for Measuring Serum Hyaluronic Acid: For the Diagnosis of Rheumatoid Arthritis

Original Article

Diagnostic Immunology

Laboratory Medicine Online 2014; 4(2): 98-104.

Published online: 1 April 2014

DOI: https://doi.org/10.3343/lmo.2014.4.2.98

Evaluation of Automated Assays for Measuring Serum Hyaluronic Acid: For the Diagnosis of Rheumatoid Arthritis

Mi-Soon Han, M.D., Yongjung Park, M.D., Hyon-Suk Kim, M.D.

Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Corresponding author: Hyon-Suk Kim. Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2228-2443, Fax: +82-2-364-1583, kimhs54@yuhs.ac

Received 14 February 2013 Revised 4 June 2013 Accepted 14 June 2013

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Hyaluronic acid (HA) is present in the connective tissues wherein it functions as a lubricant. HA is known to be increased in both synovial fluid and serum when inflammation occurs in the joint. We measured serum HA concentrations by automated assays and determined its reference interval and its usefulness as a diagnostic marker in patients with rheumatoid arthritis (RA).

Methods

Serum specimens collected from 121 healthy individuals and 253 patients with various arthritis were used for measuring HA with two automated assays, namely, LPIAACE (Mitsubishi, Japan) and LT Auto Wako (Wako, Japan). The association between serum HA concentration and the diagnosis of RA was estimated by receiver operator characteristic (ROC) analysis and multivariate logistic regression.

Results

The 95th percentile upper reference limit of serum HA was 57.28 ng/mL (90% confidence interval [CI], 46.30-68.20 ng/mL) for LPIAACE and 72.64 ng/mL (90%% CI, 57.30-85.70 ng/mL) for LT Auto Wako. Area under the ROC curve values of serum HA for discriminating the RA group from the non-RA group were 0.68 for LPIAACE and 0.70 for LT Auto Wako. The odds ratio for serum HA in predicting RA was 1.02 (95% CI, 1.02-1.04) for LPIAACE and 1.03 (95% CI, 1.02-1.05) for LT Auto Wako.

Conclusions

This study provides a reference interval for serum HA concentrations in Koreans. This result suggests that the serum HA concentrations could be helpful as a complementary marker for discriminating RA from other types of arthritis, as well as distinguishing patients with RA from healthy controls.

Keywords: Hyaluronic acid, Rheumatoid arthritis, Automated assay

Figures and Tables

Fig. 1

Levels of serum HA among patients with RA, OA, arthritis excluding RA and OA, and healthy subjects. (A) LPIAACE; (B) LT Auto Wako. The upper and lower ends of boxes and box inner lines correspond to the 3rd and 1st quartiles and median values, respectively. Error bars denote minimum and maximum values, and circles indicate outlier values.

Abbreviations: HA, hyaluronic acids; RA, rheumatoid arthritis; OA, osteoarthritis.

Fig. 2

ROC curves for serum concentration of HA in discriminating RA from unspecific arthritis. The AUCs are 0.68 (95% CI, 0.62-0.75; P<0.0001) and 0.70 (95% CI, 0.64-0.76; P<0.0001) for LPIAACE and LT Auto Wako, respectively.

Table 1

Precision performances of two assays in measuring serum hyaluronic acid

Abbreviation: QC, quality control.

Table 2

Characteristics and serum hyaluronic acid concentrations of the healthy individuals and arthritis patients

^*Data are shown as median (1st to 3rd quartiles). Sex and age between the study groups were evaluated by chi-square and Kruskal-Wallis tests, respectively.

Abbreviations: RA, rheumatoid arthritis; JRA, juvenile rheumatoid arthritis; OA, osteoarthritis; HA, hyaluronic acid.

Table 3

Results of multivariate analysis for discriminating rheumatoid arthritis patients (N=117) from healthy subjects (N=121)

Abbreviations: CI, confidence interval; HA, hyaluronic acid.

Notes

This article is available from http://www.labmedonline.org

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