HRR as a Novel Biomarker in Sjögren's Syndrome

HRR as a Novel Plasma Inflammatory Biomarker in Sjögren's Syndrome: Findings From a Case-control Study

Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic salivary and lacrimal gland dysfunction leading to dry mouth (xerostomia) and dry eye (xerophthalmia) sensation (1). Although dry mouth and dry eye are the main symptoms, the disease may influence many organs and systems. Diagnosis is made with ocular surface staining scores, anti-SS-A/SS-B auto-antibody positivity, and minor salivary gland biopsy (2). The Complete blood count (CBC) is a simple, inexpensive, accessible, and routinely used laboratory parameter that can be linked to oxidative stress, inflammation and microvascular flow resistance. Parameters include NLR and PLR values may be calculated by using CBC parameters (3). Neutrophil/lymphocyte ratio is used as an inflammatory marker in the diagnosis and prognosis of many cardiovascular diseases, malignancies, and infections (4-6). Peripheral inflammatory biomarkers of hematologic indices had been suggested by numerous studies to play a role during SS onset and progression.

Study Overview

• Status: Completed
• Conditions: Sjögren's Syndrome
• Intervention / Treatment: Other: blood sample analysis

Detailed Description

Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic salivary and lacrimal gland dysfunction leading to dry mouth (xerostomia) and dry eye (xerophthalmia) sensation (1). Although dry mouth and dry eye are the main symptoms, the disease may influence many organs and systems. Diagnosis is made with ocular surface staining scores, anti-SS-A/SS-B auto-antibody positivity, and minor salivary gland biopsy (2). The Complete blood count (CBC) is a simple, inexpensive, accessible, and routinely used laboratory parameter that can be linked to oxidative stress, inflammation and microvascular flow resistance. Parameters include NLR and PLR values may be calculated by using CBC parameters (3). Neutrophil/lymphocyte ratio is used as an inflammatory marker in the diagnosis and prognosis of many cardiovascular diseases, malignancies, and infections (4-6). Peripheral inflammatory biomarkers of hematologic indices had been suggested by numerous studies to play a role during SS onset and progression.

Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases. SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis.

Obviously, a prerequisite step in answering this critical question was to depict the change of inflammatory biomarkers of hematologic indices and disease activity progression in a detailed and comprehensive manner, and actually there were several studies aimed at answering this question. Along the hematologic indices field, most of the studies agreed that RDW was critical parameter in SS activity indication.

As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. have been shown to be a good serum marker in primary SS (pSS). All these indicated a potential linkage between systemic inflammation and the risk of SS. However, sparse evidence has been available on this association between the hematologic indices and SS. The aim of the present study, therefore, was to evaluate the association between systemic inflammation indices and SS.

• Study Type: Observational
• Enrollment (Actual): 89

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • TianJin eye hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 89 SS patients and 89 age- and gender-matched healthy subjects were included. Eighty-nine primary SS patients who met the 2012 American College of Rheumatology (ACR-2012) classification criteria and 89 healthy controls were enrolled.

Description

Inclusion Criteria:

• must meet the 2012 American College of Rheumatology classification criteria,
• without systemic diseases, such as hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease,
• without malignant tumors,
• without renal failure,
• without liver diseases,
• without anemia,
• without smoking and alcohol consumption,
• without active infection,
• without other autoimmune diseases,
• without medicine usage that could influence the blood coagulation state,
• without a history of concurrent ocular diseases or trauma,
• without any surgery within three months.

Exclusion Criteria:

• systemic diseases, such as hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease,
• malignant tumor,
• renal failure,
• liver diseases,
• anemia,
• smoking and alcohol consumption,
• active infection,
• other autoimmune diseases,
• medicine usage that could influence the blood coagulation state,
• a history of concurrent ocular diseases or trauma,
• any surgery within three months.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
89 SS patients; The medical records were analyzed retrospectively about the 89 patients with first onset of SS (SS group)	Other: blood sample analysis; All subjects went through a routine ocular examination, and the peripheral venous blood samples were collected and analyzed
89 healthy control subjects; The medical records were analyzed retrospectively about the 89 age- and gender-matched individuals (Control group) who presented with normal control.	Other: blood sample analysis; All subjects went through a routine ocular examination, and the peripheral venous blood samples were collected and analyzed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRR	hemoglobin-to-red cell distribution width ratio	change from baseline at 24 months

Collaborators and Investigators

• Sponsor: Tianjin Eye Hospital
• Investigators: Study Chair: Yan Wang, Tianjin Eye Hospital and Eye Institute, Nankai University Affiliated Eye Hospital

Publications and helpful links

General Publications

• Psianou K, Panagoulias I, Papanastasiou AD, de Lastic AL, Rodi M, Spantidea PI, Degn SE, Georgiou P, Mouzaki A. Clinical and immunological parameters of Sjogren's syndrome. Autoimmun Rev. 2018 Oct;17(10):1053-1064. doi: 10.1016/j.autrev.2018.05.005. Epub 2018 Aug 10.
• Yildiz F, Gokmen O. Haematologic indices and disease activity index in primary Sjogren's syndrome. Int J Clin Pract. 2021 Mar;75(3):e13992. doi: 10.1111/ijcp.13992. Epub 2021 Jan 19.
• Hu ZD, Sun Y, Guo J, Huang YL, Qin BD, Gao Q, Qin Q, Deng AM, Zhong RQ. Red blood cell distribution width and neutrophil/lymphocyte ratio are positively correlated with disease activity in primary Sjogren's syndrome. Clin Biochem. 2014 Dec;47(18):287-90. doi: 10.1016/j.clinbiochem.2014.08.022. Epub 2014 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2020
• Primary Completion (Actual): November 21, 2022
• Study Completion (Actual): November 21, 2022

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 30, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: KY202226

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No