Elevated levels of fractalkine expression and accumulation of CD16+ monocytes in glomeruli of active lupus nephritis.

Abstract

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.

• Authors: Shuhei Yoshimoto, Kimihiko Nakatani, Masayuki Iwano, Osamu Asai, Ken-ichi Samejima, Hirokazu Sakan, Miho Terada, Koji Harada, Yasuhiro Akai, Hideo Shiiki, Masato Nose, Yoshihiko Saito
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 50 Issue 1 Pg. 47-58 (Jul 2007) ISSN: 1523-6838 [Electronic] United States
• PMID: 17591524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CX3CL1 protein, human
• Chemokine CX3CL1
• Chemokines, CX3C
• Membrane Proteins
• Receptors, IgG

Topics

• Adolescent
• Adult
• Aged
• Chemokine CX3CL1
• Chemokines, CX3C (metabolism)
• Cross-Sectional Studies
• Female
• Humans
• Kidney Glomerulus (immunology, metabolism, pathology)
• Leukocyte Count
• Lupus Nephritis (immunology, metabolism, pathology)
• Male
• Membrane Proteins (metabolism)
• Middle Aged
• Monocytes (immunology, metabolism)
• Receptors, IgG (metabolism)
• Retrospective Studies