Dataset Information

Kidney injury in response to crystallization of calcium oxalate leads to rearrangement of the intrarenal T cell receptor delta immune repertoire.

ABSTRACT:

Background

Calcium oxalate (CaOx), the major constituent of most kidney stones, induces inflammatory infiltration and injures renal tubular cells. However, the role of ??T cells in CaOx-mediated kidney injury remains unclear. Therefore, this study investigated the distribution of intrarenal ??T cells and T cell receptor ? (TCR?) immune repertoires in response to interactions with CaOx crystals.

Methods

CaOx crystal mouse model was established by glyoxylate injection. Flow cytometer was used to analyze the expression of CD69 and IL-17 from intrarenal ??T cells. Furthermore, TCR immune repertoire sequencing (IR-Seq) was used to monitor the profile of the TCR? immune repertoire.

Results

Our results indicated that CaOx crystals lead to obvious increases in the expression and activation of intrarenal ??T cells. In TCR? immune repertoire, the majority of V/J gene and V-J/V-D-J combination segments, barring individual exceptions, were similar between kidneys with CaOx formation and control kidneys. Impressively, high complementarity determining region 3 (CDR3) diversity was observed in response to CaOx crystal formation along with distinct CDR3 distribution and abundance.

Conclusion

Our work suggests the presence of aberrant ??T cell activation and reconstitution of the TCR? immune repertoire in response to CaOx crystal deposition.

SUBMITTER: Zhu C

PROVIDER: S-EPMC6704580 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Kidney injury in response to crystallization of calcium oxalate leads to rearrangement of the intrarenal T cell receptor delta immune repertoire.

Zhu Chao C Liang Qing Q Liu Yaqun Y Kong Deliang D Zhang Jie J Wang Hu H Wang Kejia K Guo Zhiyong Z

Journal of translational medicine 20190822 1

<h4>Background</h4>Calcium oxalate (CaOx), the major constituent of most kidney stones, induces inflammatory infiltration and injures renal tubular cells. However, the role of γδT cells in CaOx-mediated kidney injury remains unclear. Therefore, this study investigated the distribution of intrarenal γδT cells and T cell receptor δ (TCRδ) immune repertoires in response to interactions with CaOx crystals.<h4>Methods</h4>CaOx crystal mouse model was established by glyoxylate injection. Flow cytomete ...[more]

PMID: 31438987

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Project description:An indole-reacted calcium oxalate crystallization index (iCOCI) test was developed to quantify the total competence of urine to precipitate calcium oxalate (CaOx) crystals. We conducted the prospective cohort study in accordance with the STARD guideline to evaluate the accuracy of urinary iCOCI test (index test) for diagnosing urolithiasis. A total of 281 participants were recruited for the study. Levels of urinary iCOCI were determined in the pre-diagnostic 24-h urine samples. Positive urinary iCOCI (? 0.6 COM eqv., g/L) was accounted for 51% (144/281), and the rest of 49% (137/281) were negative. Non-contrast CT imaging (reference standard) was subsequently performed for the definite diagnosis of urolithiasis to divide the participants into two groups, non-stone subjects (NSS, n?=?122) and stone-forming subjects (SFS, n?=?159). It should be noted that only subjects who currently had urinary stone at the time of study were classified as SFS. Urinary iCOCI levels in the SFS were significantly higher than the NSS. ROC analysis revealed an area under curve (AUC) of 0.893 (95% CI: 0.855-0.932) in separating NSS from all SFS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (LH+) and negative likelihood ratio (LH-) of urinary iCOCI test for diagnosis of all urolithiasis were 87%, 80%, 84%, 84%, 83%, 4.44 and 0.16, respectively. Of 159 SFS, 38 were confirmed to have CaOx stones. Among these 38 CaOx SFS, only 2 had negative urinary iCOCI test. The AUC of urinary iCOCI test for separating CaOx SFS from NSS was markedly high (0.946, 95% CI: 0.914-0.978). Sensitivity, specificity, PPV, NPV, accuracy, LH+ and LH- of urinary iCOCI test for diagnosing CaOx urolithiasis were 95%, 86%, 68%, 98%, 88%, 6.80 and 0.06, respectively. Conclusion, we clinically validated that an innovative non-invasive urinary iCOCI test was highly accurate to diagnose urolithiasis, especially CaOx stone. With its high sensitivity and NPV, urinary iCOCI test is clinically intended to use as a screening test for CaOx urolithiasis. LH- of 0.06 indicates that negative result of urinary iCOCI test is highly accurate to rule out the CaOx stone formation. It is noted that urinary iCOCI level is expressed as arbitrary unit, and it is not directly related to the actual physiological level of urinary oxalate.

Dataset Information

Kidney injury in response to crystallization of calcium oxalate leads to rearrangement of the intrarenal T cell receptor delta immune repertoire.

Background

Methods

Results

Conclusion

Publications

Kidney injury in response to crystallization of calcium oxalate leads to rearrangement of the intrarenal T cell receptor delta immune repertoire.

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