**3. Novel Biomarkers**

ATIN involves cell immunity rather than humoralmechanisms, as suggested by the extensive and pleiomorphic inter-tubular cell infiltrate in ATIN kidney biopsies, with lack of immune deposits in most of the cases. Rarely anti-tubular basal membrane (TMB) antibodies and immune complexes can be noticed. The presence of this immune cell infiltration can damage TECs due to direct cytotoxicity or local cytokine release. At the same time, TECs acquire an active role in inflammation by orchestrating the immune response and directly producing diverse cytokines. In the same line, cell infiltrates together with activated TECs also produce signaling molecules that promote matrix deposition and remodeling, thus promoting fibrosis [17].

Identification of the differential nature of the tubulointerstitial infiltrates in ATIN and the cytokines produced by this infiltrate—in comparison to other inflammatory kidney diseases—and their detection in serum or urine, can be useful as biomarkers of the disease.
