A STEINBERG1, F CHOW1, S HOLT1, A TUCKFIELD2, M FINLAY3, T BARBOUR1
1Department of Nephrology, Royal Melbourne Hospital, Parkville, Australia, 2Department of Haematology, Peter MacCallum Cancer Centre, Parkville, Australia, 3Department of Anatomical Pathology, Royal Melbourne Hospital , Parkville, Australia
Background: C3 glomerulopathy (C3G) is characterised by predominant glomerular C3 staining, with amorphous dense deposits on electron microscopy (EM). Monoclonal gammopathy is sometimes present, including rare cases in which monoclonal immunoglobulin (Ig) or free light chain (FLC) has been shown to trigger complement activation via the alternative pathway (AP). By contrast, immunotactoid/fibrillary implies organised glomerular deposits (fibrils/tubules) on EM, with immune reactivity for IgG (with or without C3). The IgG in immunotactoid is frequently monotypic, and this lesion is strongly associated with malignant B cell disorders (myeloma, lymphoma, chronic lymphocytic leukaemia).
Case Report: A 42-year old, previously well Caucasian man presented with nephrotic syndrome (protein to creatinine ratio 587mg/mmol; serum albumin 26g/L), active urine sediment (erythrocytes 169×106/L; leukocytes 347×106/L) and mild renal impairment (creatinine 110umol/L). ANA, ENAs, dsDNA, ANCAs, cryoglobulins, RF, viral hepatitis serology, C3, C4, CH100 and C3 nephritic factor were negative (FH autoantibody was not sent). Kappa FLCs were markedly elevated in serum (2.4g/L; ratio to lambda 275) and urine. Renal biopsy showed a membranoproliferative pattern, Congo red negative, with moderate granular mesangial and capillary loop staining for C3c and fibrin (negative IgG, IgA, IgM and C1q; insufficient tissue for kappa and lambda). EM revealed long fibrils (diameter 60-80nm without definite tubular structure) arranged in bundles throughout the mesangium and subepithelial space (also subendothelial and intramembranous). Bone marrow biopsy showing 20% aberrant plasma cells led to autologous stem cell transplantation. The renal clinical abnormalities promptly resolved (U/PCR 7mg/mmol), with myeloma in remission at 2 years.
Conclusions: We speculate that the fibrils contained monoclonal kappa FLC precipitates, triggering local AP activation and giving the novel appearance on immune staining (but not EM) of C3G.
Adam is a second-year advanced trainee in nephrology based at the Royal Melbourne Hospital.