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Abstract: SA-PO1038

Urinary Immune Complex of V-Set Immunoglobulin Domain-Containing 4 as a Novel Biomarker of Lupus Nephritis

Session Information

Category: Pathology and Lab Medicine

  • 1800 Pathology and Lab Medicine

Authors

  • Wu, Tianfu, University of Houston, Houston, Texas, United States
  • Saxena, Ramesh, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Lupus nephritis (LN) is a devastating chronic kidney disease (CKD) caused by Systemic lupus erythematosus (SLE). However, to monitor disease activity and predict the risk of LN flare is still challenging, and there is an urgent need to identify novel biomarkers of LN that have high diagnostic or predictive values. In our recent study, by using a quantitative proteome immunoarray, V-set Immunoglobulin-domain-containing 4 (VSIG4) was found siginifcantly elevated in the serum and kidneys of LN patients compared to healthy controls, and could reflect renal pathology of LN. We were interested to ask if VSIG4 was secreted into the urine in LN patients.

Methods

In an intial testing using ELISA, we simultaneously measured the free form, autoantibody, and immune complex levels of VSIG4 in the urine and serum samples from the same LN patients (N = 28), compared to other chronic kidney disease controls (CKD, N = 7) and healthy controls (N = 13).

Results

We found that the free form of VSIG4 was not detectable in the urine of LN or controls by using commercial sandwich ELISA kits. Interestingly, the urinary immune complex of VISG4 (VSIG4 ICx) was detectable in LN and controls. Importantly, the urinary VSIG4 ICx was significantly elevated in the LN patients, compared CKD controls (P-value = 0.031) and healthy controls (P-value = 3.05E-05). Urinary VSIG4 ICx was also significantly increased in the CKD patients compared to healthy controls (P-value = 2.58E-05). In the same patients, the free form of VISIG4 was significantly elevated in LN, compared to CKD contorls (P-value = 2.6E-05) and healthy controls (P-value = 1.14E-10); both serum autoantibody and serum ICx levels of VSIG4 were also significantly elevated in LN compared to healthy controls. By using a Spearman's paired test, the urinary VSIG4 ICx levels were positively correlated with the serum free-form VSIG4 levels ( r = 0.67, p < 0.001). More interestingly, the urinary VSIG4 ICx levels were positively correlated with the following clinical parameters: SLEDAI (Spearman's Rank Correlation Coefficient rs = 0.49, p = 0.007), rSLEDAI (rs = 0.44, p = 0.03), urine protein/creatinine (rs = 0.4, p = 0.03), and white blood cell counts (rs =0.49, p = 0.04).

Conclusion

Urinary VSIG4 immune complex may be a promising novel biomarker of SLE and LN.

Funding

  • Other NIH Support