American Journal of Kidney Diseases
Volume 50, Issue 1 , Pages 47-58, July 2007

Elevated Levels of Fractalkine Expression and Accumulation of CD16+ Monocytes in Glomeruli of Active Lupus Nephritis

  • Shuhei Yoshimoto, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Kimihiko Nakatani, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
    • Corresponding Author InformationAddress correspondence to Kimihiko Nakatani, MD, First Department of Internal Medicine, Nara Medical University, 840, Shijo-cho, Kashihara-city, Nara, 634-8522, Japan.
  • ,
  • Masayuki Iwano, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Osamu Asai, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Ken-ichi Samejima, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Hirokazu Sakan, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Miho Terada

      Affiliations

    • Department of Pathology, Division of Pathogenomics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
  • ,
  • Koji Harada, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Yasuhiro Akai, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Hideo Shiiki, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara
  • ,
  • Masato Nose, MD

      Affiliations

    • Department of Pathology, Division of Pathogenomics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
  • ,
  • Yoshihiko Saito, MD

      Affiliations

    • First Department of Internal Medicine, Nara Medical University, Kashihara, Nara

Received 2 November 2006; accepted 19 April 2007.

Background

Fractalkine (Fkn) is a chemokine that affects cells expressing its receptor, CX3CR1, including CD16-positive (CD16+) monocytes/macrophages (CD16+ Mos). The relationship of levels of glomerular Fkn expression and infiltration by CD16+ Mos with the severity and diversity of glomerular lesions in human lupus nephritis is not known.

Study Design

Retrospective cross-sectional analysis of variables observed in biopsy specimens.

Settings & Participants

88 patients with systemic lupus erythematosus.

Predictor

Histological class and severity of lupus nephritis according to the International Society of Nephrology/Renal Pathology Society and clinicopathologic factors.

Outcomes

Outcome variables are assays related to the degree of glomerular Fkn expression and CD16+ Mo infiltration.

Measurements

Immunohistological grading of Fkn staining, number of CD16+ Mos, and messenger RNA levels of Fkn and CD16 in glomeruli.

Results

Patients with proliferative lupus nephritis (class III and IV glomeruli) showed significantly greater glomerular Fkn expression and CD16+ Mo counts than those with other classes. Infiltrating CD16+ Mos within glomeruli expressed CX3CR1. Moreover, glomerular Fkn expression significantly correlated with the histopathologic activity index and CD16+ Mo counts, and CD16+ Mo counts significantly correlated with serum levels of blood urea nitrogen, complement (CH50), and anti-DNA antibody; estimated glomerular filtration rate; and urinary protein excretion. Glucocorticoid therapy had a tendency to decrease both glomerular Fkn expression and CD16+ Mo counts.

Limitations

Only frozen biopsy specimens (from 49 patients) were analyzed for the evaluation of glomerular Fkn expression.

Conclusion

Disease activity and proliferative glomerular lupus nephritis lesions are associated with the glomerular Fkn expression and CD16+ Mo accumulation.

Index Words: Fractalkine, lupus nephritis, CD16+ monocytes

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PII: S0272-6386(07)00735-4

doi:10.1053/j.ajkd.2007.04.012

American Journal of Kidney Diseases
Volume 50, Issue 1 , Pages 47-58, July 2007