Only 46% of patients with IgMPC-TIN satisfied the criteria for PBC, whereas 31% satisfied the criteria for Sj?gren syndrome. TIN presented with IgM-positive plasma cells. tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and colocalized IgM-positive Dimethocaine plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3?-Cl? Dimethocaine anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cellCtubulointerstitial nephritis. Dimethocaine and anti-light chain antibodies (Supplemental Physique 3), but no monoclonality was confirmed. The averaged quantity of infiltrating IgM-positive plasma cells per high-power field (hpf) of renal interstitium from patients with IgMPC-TIN was markedly higher than from patients with other forms of TIN chosen as controls for staining (15 TIN with Sj?gren syndrome, 12 with IgG4-related kidney disease, three with TIN with ANCA-related vasculitis, three with granulomatous TIN, four with drug-related TIN, one with antibody-mediated rejection, two with chronic pyelonephritis, and four Dimethocaine with unknown TIN) (observe Concise Methods section for details) (Physique 3, Supplemental Physique 2I). Receiver operating characteristic (ROC) curve analysis revealed that optimal predictive cutoff number for infiltrating IgM-positive plasma cells was 13 per hpf, with an Dimethocaine area under the ROC curve of 0.99 (95% confidence interval [95% CI], 0.979 to 1 1.007; autoantibodies) commonly observed in autoimmune conditions such as PBC and Sj?gren syndrome.32 Similarly, CCD tubulitis with CD3-positive T lymphocytes may also cause pump failure. However, the precise mechanism underlying d-RTA in patients with IgMPC-TIN is unknown. Glucosuria is a potential symptom in Fanconi syndrome due to proximal tubular dysfunction. This proximal tubular dysfunction may be caused by proximal tubulitis with CD3-positive T lymphocytes, which is the same mechanism that underlies the aforementioned CCD dysfunction. Because the bicarbonate-loading test was not performed in all of our patients, we can only speculate about the potential occurrence of concomitant proximal-RTA. The possibility that AMAs lead to Fanconi syndrome/TIN in patients with PBC due to mitochondrial cytopathy was previously discussed.11 However, additional studies will be required to determine whether AMAs can be a direct cause of mitochondrial cytopathy, because AMAs likely have no pathogenic role in patients with PBC.33 At present, we are assuming the relations among IgMPC-TIN, PBC, and Sj?gren syndrome are as shown in Figure 7. Open in a separate window Figure 7. Relations among IgMPC-TIN (red) and overlapping diseases. Only 46% of patients with IgMPC-TIN satisfied the criteria for PBC, whereas 31% satisfied the criteria for Sj?gren syndrome. TIN presented with IgM-positive plasma cells. Infiltration of IgG-positive plasma cells is a common finding in TIN, including IgG4-related kidney disease.4 By contrast, infiltration of IgM-positive plasmacytoid lymphocytes is very rare.5 Although CD138 is a better and more specific marker of plasma cells6 than CD38, plasmablasts, immature plasma cells, and mature plasma cells all stained positively for CD138.34 Generally, antigen-activated B cells with T cell help undergo affinity maturation within germinal centers and persist as long-lived IgG plasma cells in the bone marrow. Thus, CD138-positive mature plasma cells secrete IgG, but not IgM. However, it was recently reported that short-lived IgM-positive plasmablasts develop into long-lived IgM-positive mature plasma cells.8 We observed that many IgM-positive cells also stained positively for CD138, which suggests that IgM-secreting cells in the renal interstitium are long-lived mature plasma cells or short-lived plasmablasts. Long-lived IgM-positive plasma cells were not antigen-selected, and IgM secreted from these cells could potentially provide protective host immunity against lethal conditions.8 On the other hand, IgM-positive plasmablasts reportedly exert inhibitory effects (regulatory B cell) IL-10 production,35 and infiltrating IgM-positive cells may act to protect against interstitial inflammation. Precisely distinguishing between IgM-positive plamablasts and mature plasma cells is difficult due to the commonality of these cell markers (B lymphocyteCinduced maturation protein-1: Blimp-1; interferon-regulatory factor 4: IFR4; and X-boxCbinding protein 1: XBP1).34 In patients with PBC, immunohistochemical examination has clarified that the cells infiltrating portal tracts are IgM-positive.36C38 The environmental niche of long-lived CD38-positive plasma cells and their effect on inflammation may have important implications for PBC.39 In our study, we confirmed that cells infiltrating the portal tract in patients with PBC Rabbit Polyclonal to PPP4R2 are IgM-positive and stain positively for CD138, which is also the case for cells infiltrating the renal interstitium in patients with IgMPC-TIN. Although the precise.
