Dana Kidder

Kidney biopsy findings in primary Sjögren syndrome

BACKGROUND Renal involvement is rare in primary Sjögren syndrome (PSS). In this study, we examined renal biopsy findings in patients with PSS and correlated them with their clinical and renal findings. METHODS Twenty-five patients with PSS who underwent renal biopsies from two renal units in Scotland between 1978 and 2013 were identified from renal biopsy database. We examined the renal morphologic, clinical and renal findings at the time of renal biopsy, renal and patient outcomes. RESULTS The diagnosis of PSS preceded renal biopsy in 18/25 patients. In this group, the median duration of the disease was 5.5 years. Significant proteinuria, combined microscopic haematuria and proteinuria and reduced renal excretory function were found in 76, 56 and 84% of patients, respectively. The 3-year actuarial patient survival was significantly lower in patients with glomerulonephritis as compared with tubulointerstitial nephritis (66 versus 100%, P = 0.02). There was no difference in 3-year actuarial renal survival between these two groups (92 versus 92%, P = 1.0). CONCLUSIONS Renal biopsy is rare in PSS and often reveals diverse pathological findings. Glomerulonephritis, as compared with tubulointerstitial nephritis, is associated with higher early mortality. Further studies are needed to evaluate the utility of renal biopsy and its impact on disease management.

Treg17 cells are programmed by Stat3 to suppress Th17 responses in systemic lupus

To the Editor: Kluger et al. reported their findings on Stat3 requirement in regulatory T cell (Treg)–mediated suppression of Th17 responses in pristane-induced lupus using Tregspecific Stat3 deletion (Foxp3 Stat3). An exaggerated pulmonary capillaritis was observed at 4 to 6 weeks in Stat3-deficient mice. Mortality in Foxp3 mice was observed at 5 months, and it was significantly less compared to that in knock out mice. This early mortality in Foxp3 Stat3 mice is unlikely to be related to deficient Treg responses and might be explained better by innate immune responses, primarily TLR7 activation. Pristane-induced lupus, similar to human systemic lupus erythematosus, is characterized by the presence of “interferon signature.” Pristane can also induce interferon alfa production through the TLR7/ MyD88 pathway. A study analyzing disease severity using Foxp3 Stat3 crossed with TLR7 mice might help to explain the innate immune response contribution to the early mortality observed in this study. The severity of the renal injury reported by Kluger et al. was pronounced in Foxp3 Stat3 compared to Foxp3 mice. It is unclear whether there was a difference in the onset of nephritis in these mice, as no data of urine protein estimation were available. The frequency of interleukin-17þ T effectors was found to be significantly elevated in Foxp3 Stat3 compared to wild-type mice at 4 months. This pattern continued to be significant at 9 months when Th1 responses (interferon gamma– positive T effectors) were also more frequent in Foxp3 Stat3. It is possible that the severity of the renal injury in knockout mice was related to early disease onset due to earlier Th17-mediated injury secondary to failed regulation by Tregs. Finally, higher expression of interleukin-6 and transforming growth factor-b was previously reported to be directly related to Stat3 deficiency. It is unclear whether there were any differences in interleukin-6 levels between wild-type and Stat3-deficient mice in this disease model.

Correction to: Late-onset Pneumocystis jirovecii pneumonia (PJP) in patients with ANCA-associated vasculitis

The family name of the corresponding author on this article was incorrectly spelled as “El Hakem Matraiah”. The correct spelling should have been “El Hakem Metraiah”. This is now presented correctly in this article.

Deceiving proteins! A case of lymphoma and high creatinine

Estimation of kidney function by measuring serum creatinine is one the commonest laboratory tests conducted in clinical practice. Enzymatic methods are often used to measure serum creatinine. Clinicians should be aware of the limitations of these methods, such as test interference with paraproteins.We present a case of falsely elevated serum creatinine in a patient referred for renal biopsy. The combination of fluctuating creatinine and normal blood urea level was unusual. Serum protein electrophoresis revealed the presence of an IgM paraprotein. Further investigations confirmed an underlying diagnosis of lymphoplasmacytoid lymphoma. This case highlights how IgM paraprotein can interfere with creatinine estimation by enzymatic assay and the utility of alternative methods of estimating serum creatinine.

Differences in the frequency of macrophage and T cell markers between focal and crescentic classes of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis

Background Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) can be classified into; focal, crescentic, mixed and sclerotic classes. Macrophages and T lymphocytes are key players in mediating renal injury. The frequency of macrophage and T lymphocytes in different histological classes is unclear. Objectives We examined the frequency of macrophage and T lymphocyte markers in AAGN and assessed their correlation with renal function at presentation. Patients and Methods Renal biopsies from 38 patients were included in immunohistochemistry analysis of macrophages (CD68, sialoadhesin [Sn] and mannose receptor [MR]) and T cells (CD4 and CD8) markers. The frequency of these markers in glomerular, periglomerular and interstitial compartments were measured in a blinded fashion. Biopsies were allocated a histological class of focal, crescentic, mixed or sclerotic. Scores were then matched to histological class and assessed for correlation with renal function. Results The biopsies were crescentic 19 (50%), focal 10 (26.3%), mixed 6 (15.7%) and sclerotic 3 (8%). Interstitial CD68+ macrophages and CD8+ T lymphocytes showed best correlation with renal function at the time of presentation. CD68+ macrophages were significantly increased in crescentic compared to focal AAGN. MR+ macrophages, CD4 and CD8 T cells were also elevated in the interstitium of crescentic compared to focal group. Conclusions In this study interstitial CD68 and CD8 showed the highest association with the renal function at presentation. Differences in the cellular infiltrate between focal and crescentic AAGN were related to CD68+ macrophages and to interstitial MR+ macrophages and T lymphocytes. Further studies are needed to assess these differences across all four histological categories.