#2984 SLE associated fibrillary glomerulonephritis vs SLE nephritis with fibrils: can a straightforward distinction always be made?

Abstract Background and Aims Fibrillary glomerulonephritis (FGN) is an uncommon but serious kidney disease with unclear aetiology, variable prognosis, and a not well-established treatment. FGN has been associated with autoimmune diseases including SLE. Other aetiologies comprise diabetes, malignancies, HCV and chronic infections. Our goal is to discuss the pathologic and clinical differential diagnosis conundrums that a patient with a suspected SLE presented. Method We present the case of a 53-year-old woman evaluated for proteinuria (1 g/24 h), and glomerular haematuria. Renal function was normal. She referred mild arthralgias for the past two years. Her medical history was unremarkable for diabetes and hypertension. ANA and anti-dsDNA were positive. The rest of the immunological work-up was normal as well as protein immunofixation/free light chains. HCV, HBV, and HIV serology was negative. A thorough evaluation for malignancy was negative. A renal biopsy was performed. Results The renal biopsy showed enlarged glomeruli with mesangial matrix expansion (Congo-red negative), mild mesangial hypercellularity and focal endocapillary hypercellularity without hyaline deposits, fibrinoid necrosis or crescents, without significant chronic lesions (Fig. 1). A probable diagnosis based on light microscope could be that of a lupus nephritis class III with low activity and low chronicity indices. Immunofluorescence demonstrated weak or moderate immunofixation of IgG (2+), IgA(1+), C3(2+), C1q(1+), κ(1+) and λ(1+) in the mesangium and segmentally in the capillary walls with a smudgy appearance. IgM, C4, fibrinogen and albumin were negative. The lack of a full-house pattern and, more significantly, the low C1q intensity raised some questions about the validity of a lupus nephritis diagnosis. Ultrastructural evaluation revealed abundant fibrils that occupied the mesangium and permeated the glomerular basement membranes (GBMs). Fibrils were non branching and randomly oriented with a mean diameter of ∼15 nm (range: 11,87 nm -18,84 nm) (Fig. 2). No electron dense deposits, fingerprint deposits or tubuloreticular inclusions were detected. Immunohistochemical staining for DNA-J heat-shock protein family member B9 (DNAJB9) was then performed showing strong positivity in the mesangial matrix and GBMs. Interestingly, C4d was also strongly positive with the same pattern as DNAJB9. The diagnosis of fibrillary glomerulonephritis was suggested, mostly based on ultrastructural evaluation and immunohistochemical findings. Conclusion It is well known that the characteristic features of lupus nephritis (intense C1q staining, full-house staining, extraglomerular deposits, tubuloreticular inclusions, and combined subendothelial and subepithelial deposits) are, in some cases, neither universally present nor specific for lupus nephritis. Of special interest is the identification of fibrils in the renal biopsy of an SLE patient. The crucial importance of distinguishing between SLE associated FGN and SLE nephritis with fibrils is based on the generally poor renal prognosis of FGN as well as the unsatisfactory performance of immunosuppression. The differential diagnosis can be very challenging especially when DNAJB9 is not available.