CXCR3+CD4+ T cells are enriched in inflamed kidneys and urine and provide a new biomarker for acute nephritis flares in systemic lupus erythematosus patients.
OBJECTIVE
The high frequency of CD4+ T cells in interstitial infiltrates of patients with lupus nephritis suggests a contribution of these cells to local pathogenesis. The aim of this study was to examine the role of CXCR3 and the chemokine CXCL10 in recruiting these cells into the kidney and to determine whether the infiltrating T cells could be monitored in the urine to provide a reliable biomarker for acute lupus nephritis.


METHODS
The frequencies of CD3+ T cells, CXCR3+ cells, and CXCL10+ cells were determined by immunohistochemical and immunofluorescence analyses of kidney sections from 18 patients with lupus nephritis. The frequency of CXCR3+CD4+ T cells was determined by flow cytometry of peripheral blood and urine from 38 patients with systemic lupus erythematosus (SLE), and the values were compared with disease activity as determined by the Systemic Lupus Erythematosus Disease Activity Index.


RESULTS
In renal biopsy tissues from patients with lupus nephritis, a mean of 63% of the infiltrating cells expressed CXCR3, approximately 60% of them were T cells, and the CXCR3+ cells colocalized with CXCL10-producing cells. In biopsy tissues from SLE patients with acute nephritis, approximately 50% of the urinary CD4+ T cells were CXCR3+, as compared with 22% in the peripheral blood, and the frequency of urinary CXCR3+CD4+ T cells correlated with disease activity. Moreover, the number of urinary CD4+ T cells reflected nephritis activity, and elevation above 800 CD4+ T cells per 100 ml of urine sharply delineated active from inactive nephritis.


CONCLUSIONS
CXCR3+ T cells are recruited into the inflamed kidneys, are enriched in the urine, and are a valuable marker of nephritis activity in SLE. They also present a potential target for future therapies.
Enghard
P
P
Charité University Hospital, Berlin, Germany. philipp.enghard@charite.de
Humrich
J Y
JY
Rudolph
B
B
Rosenberger
S
S
Biesen
R
R
Kuhn
A
A
Manz
R
R
Hiepe
F
F
Radbruch
A
A
Burmester
G-R
GR
Riemekasten
G
G
D000208:Acute Disease; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D054367:Receptors, CXCR3 / Q000378:metabolism*; D014556:Urine / Q000166:cytology
D015415:Biomarkers; C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3