The Profile of Serum Transferrin Isoforms in Rheumatoid Arthritis

Monika Gudowska, PhD; Ewa Gruszewska, PhD; Alicja Wrona, MSc; Ewa Gindzienska-Sieskiewicz, PhD; Izabela Domyslawska, PhD; Karina Lipartowska-Klimuk, PhD; Bogdan Cylwik, PhD; Stanislaw Sierakowski, PhD; Lech Chrostek, PhD

Disclosures

J Clin Rheumatol. 2019;25(4):159-162. 

In This Article

Abstract and Introduction

Abstract

Introduction: Transferrin, a microheterogeneous iron-transporting N-glycoprotein, is an optimal model for the analysis of the glycosylation profile in rheumatoid arthritis (RA). The aim of this study was to assess the transferrin isoforms profile in RA patients at the time of diagnosis and then look into their associations with disease activity.

Methods: Serum samples were collected from 48 patients with RA. The patients were males (6) and females (42) (age range: 33–85 years). Control group consisted of 30 healthy volunteers. Transferrin isoforms were analysed by capillary electrophoresis on MINICAP electrophoretic system.

Results: There was a significant decrease in the relative concentrations of trisialo- (mean ± SD; 2.130 ± 1.112) and pentasialotransferrin (13.562 ± 3.088), and significant increase in tetrasialotransferrin (83.640 ± 3.165) in RA patients when compared to the control group (3.615 ± 1.156; 76.840 ± 5.621; 18.610 ± 6.027, respectively) (U Mann–Whitney test: p < 0.001 for all comparisons). There were no significant changes in the disialotransferrin concentrations in RA patients. Trisialotransferrin concentration correlated with RA activity expressed as DAS 28 in RA patients (p < 0.001). The low trisialotransferrin concentration was also associated with high platelet count and high ESR (p < 0.001 for both). Disialo-, tetrasialo- and pentasialotransferrin concentrations did not correlate with DAS 28.

Conclusions: In patients with RA the serum profile of transferrin isoforms is altered. We predict that the levels of trisialylated isoforms of transferrin will serve as a useful biochemical marker of the RA activity.

Introduction

Rheumatoid arthritis (RA), the most common inflammatory arthritis in human population, is a chronic autoimmune disease of connective tissues.[1,2] The disease is characterized by chronic joint inflammation, swelling, tenderness, and destruction of bone and cartilage.[3] Currently, the diagnosis of and prognosis in RA are based on the symptoms and on the measurement of the markers, including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin (Hb) and antibodies against cyclic citrullinated peptide (anti-CCP).[4,5] However, there is no single test to date to confirm the diagnosis of RA. Literature indicates that the consequences of the disease include changes in serum proteins glycosylation.[6] In this study, we chose transferrin as a model N-glycoprotein. Transferrin is composed of three structural subdomains: a single polypeptide chain and two N-linked oligosaccharide chains which determine its microheterogeneity (nine isoforms, from asialo- to octasialotransferrin).[7,8] In healthy subjects, tetrasialotransferrin predominates (64–80%).[9] Previous research by Feelders et al. showed the usefulness of analysis of the transferrin isoform profile in the diagnosis of rheumatoid arthritis.[10] These authors classified the transferrin isoforms as three fractions: the low sialylated transferrin fraction (considered by authors as a sum of asialo-, monosialo-, disialo- and trisialotransferrin), the tetrasialotransferrin fraction and the highly sialylated transferrin fraction. Nowadays, the definition of low-sialylated transferrin isoforms is changed and is defined as a sum of asialo-, monosialo- and disialotransferrin.[9] In our study, we applied a different method—a capillary electrophoresis. Therefore, the aim of this study was to assess the transferrin isoform profile: asialotransferrin, disialotransferrin, trisialotransferrin, tetrasialotransferrin, and pentasialotransferrin in rheumatoid arthritis at the time of diagnosis and to evaluate the associations of these isoforms with the disease activity.

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