Tubulointerstitial nephritis associated with IgG4-related systemic disease.

We report three patients with tubulointerstitial nephritis (TIN) with high serum IgG4 concentrations. None of the patients had notable pancreatic lesions when the TIN developed, although one had a history of autoimmune pancreatitis (AIP). Nevertheless, the clinicopathological findings were quite similar to those of AIP. They were all middle-aged to elderly men. Sialadenitis and lymphadenopathy were often evident. Serum total IgG and IgG4 concentrations were elevated and hypocomplementemia was observed. Although antinuclear antibodies were positive, anti-Ro and anti-La antibodies were negative. Renal biopsy showed dense lymphoplasmacytic infiltration with fibrosis in the renal interstitium, and the infiltrated plasma cells had strong immunoreactivity for IgG4. Furthermore, lymphoplasmacytic infiltration and abundant IgG4-positive plasma cells were observed in the salivary glands of a patient. Steroid therapy was effective for TIN in all three patients. The present findings support the recently proposed concept of IgG4-related systemic disease, and suggest that IgG4 is associated not only with AIP but also with other systemic lymphoplasmacytic diseases, including TIN. The conditions responsible for the pathogenesis of TIN need to be considered, irrespective of the presence of AIP.