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Toll-like receptor 9 in systemic sclerosis patients: relation to modified Rodnan skin score, disease severity, and functional status

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Abstract

The objective of this study is to assess toll-like receptor-9 (TLR9) expression in CD3-positive T lymphocytes and CD19-positive B lymphocytes in systemic sclerosis (SSc) patients and to study their relation to the extent of skin fibrosis, disease characteristics, and severity as well as the functional status. Fifty-five female SSc patients and 30 matched controls were included. Skin thickness was scored according to the modified Rodnan skin score (mRss). The severity of major organ involvement was assessed using the Medsger severity score (MSS). Scleroderma health assessment questionnaire (SHAQ) was measured to evaluate patients’ functional status. Expression of TLR9 in CD3-positive T lymphocytes and CD19-positive B lymphocytes was studied using flow cytometry. The mean age of the patients was 40.5 ± 9.1 years, and their disease duration was 6.7 ± 3.3 years. There were 21 (38.2%) with diffuse (dcSSc) and 34 (61.8%) with limited cutaneous (lcSSc) subtypes. There was a significant increase in the expression of TLR9/CD3 and TLR9/CD19 in the SSc patients (44.9 ± 18.1 and 24.1 ± 9.6) compared to that in the control (1.4 ± 0.97 and 1.3 ± 0.94; p < 0.0001 for both, respectively) being higher in those with dcSSc. TLR9/CD3 expression was significantly increased in SSc patients with arthralgia/arthritis and digital resorption compared to those without. The TLR9/CD3 significantly correlated with the mRss and MSS (r = 0.37, p = 0.006 and r = 0.31, p = 0.02; respectively). Both the TLR9/CD3 and TLR9/CD19 expressions were significantly correlating (r = 0.53, p < 0.0001). On regression analysis, only TLR9/CD3 was a significant risk factor of the mRss and MSS (β = 0.43, p = 0.009 and β = 0.33, p = 0.015, respectively). TLR9, especially TLR9/CD3, is highly expressed in SSc patients particularly those with dcSSc subtype and could form a potential marker for skin fibrosis and disease severity.

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Authors and Affiliations

  1. Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Tamer A Gheita, Safaa Sayed & Gada S Azkalany

  2. Rheumatology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Nouran Abaza

  3. Rheumatology and Rehabilitation Department, Faculty of Medicine, Assuit University, Asyut, Egypt

    Nevin Hammam

  4. University of Alberta, Corbett Hall, 8205 114 Street, Edmonton, AB, T6G 2G4, Canada

    Nevin Hammam

  5. Clinical and Chemical Pathology Department (Immunology), Faculty of Medicine, Helwan University, Helwan, Egypt

    AH Eissa

Authors
  1. Tamer A Gheita
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  2. Safaa Sayed
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  3. Gada S Azkalany
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  4. Nouran Abaza
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  5. Nevin Hammam
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  6. AH Eissa
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Corresponding author

Correspondence to Nevin Hammam.

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The study conforms to the 1995 Helsinki declaration and was approved by Cairo University Hospitals’ ethical committee. Informed consent was obtained from all patients.

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Gheita, T.A., Sayed, S., Azkalany, G.S. et al. Toll-like receptor 9 in systemic sclerosis patients: relation to modified Rodnan skin score, disease severity, and functional status. Clin Rheumatol 37, 757–763 (2018). https://doi.org/10.1007/s10067-017-3880-6

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  • DOI: https://doi.org/10.1007/s10067-017-3880-6

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