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A3.26 Identifying T-Follicular-Helper-Like Cell Involvement in the Organization of Tubulointerstitial Inflammation in Human Lupus Nephritis and Renal Allograft Rejection
  1. V Liarski1,
  2. D Brandt1,
  3. N Kaverina1,
  4. S Henderson1,
  5. A Chang2,
  6. T Utset1,
  7. C Labno3,
  8. Y Peng4,
  9. Y Jiang4,
  10. M Giger4,
  11. M Clark1
  1. 1Section of Rheumatology, Department of Medicine and Knapp Center for Lupus Research, University of Chicago, Chicago, IL 60637
  2. 2Department of Pathology, University of Chicago, Chicago, IL 60637
  3. 3Integrated Microscopy Core Facility and Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL 60637
  4. 4Department of Radiology, University of Chicago, Chicago, IL 60637

Abstract

Background Tubulointerstitial inflammation (TII) is a usual feature of lupus nephritis (LuN) and the infiltrate is organised into well-circumscribed T:B-cell aggregates or germinal centre-like structures.

Materials and Methods We analysed 42 LuN biopsies using confocal laser scanning microscopy (CLSM) for the qualitative presence of TFH-like CD4+ICOS+ cells (TIH)(n = 19 for ICOS-positive cases) and compared this with T-cell-mediated (TCM, n = 8) and mixed renal allograft (mixed RT, n = 7) rejection cases. Cellular make-up and relationships within TII were examined using CLSM to identify and compare the locations of TIH cells and CD20+ B cells by means of a computerised cell-distance algorithm.

Results The prevalence of TIH cells was found to be 45.2% in LuN, 64.2% in TCM, and 50% in mixed RT cases. Presence of these cells in LuN was statistically correlated with a worse grade of TII as scored by a blinded pathologist (2.05 versus 1.48, p = 0.04). ICOS-positive biopsies were associated with a higher mean serum creatinine in adult patients at time of biopsy (2.3 versus 1.1 mg/dL, p = 0.03) as well as GFR as measured by the MDRD equation and adjusted for patient sex (44.8 versus 74.1 mL/min/1.73 m2, p = 0.04) with no statistical differences in age, sex, ISN/RPS LuN class, or NIH activity or chronicity indices.

Cellular distance mapping revealed that TIH cells were spatially related to CD20+ B cells across LuN (42.9% of cells within 0.27 microns, n = 10 biopsies), control tonsil tissue (65.3%, n = 2 biopsies), and mixed RT cases (70.3%, n = 7 biopsies) as compared to other T cells (less than 20% for all groups, respectively). These associations remained unchanged after correction for total cellular density and T:B cell ratios. Low-density TCM cases showed a comparatively low rate of TIH:B cell association (15.0%, n = 8 biopsies) and these results were statistically significant (p < 0.0001 versus mixed RT and tonsil cases, p = 0.002 versus LuN). Comparing the above results against a theoretical model of random TIH:B-cell distribution revealed that the likelihood of our observations in LuN being due to chance was approximately 8.12 × 10–41.

Conclusions Our data reveal that TIH cells are present in similar rates across cases of renal allograft rejection as well as LuN. Their presence is associated with a higher degree of TII as well as worse renal function at time of biopsy in LuN. TIH cells are more likely to form proximal conjugates with naïve and activated B cells in tissues of diseases associated with aberrant autoantibody production (SLE, mixed RT) but not in processes where autoantibodies are absent (TCM).

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