Renal disease related to the deposition of monoclonal
immunoglobulins containing both heavy and light chains can occur in type 1
cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid
glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by
monoclonal gammopathy.
METHODS: Ten cases of unclassifiable proliferative
glomerulonephritis manifesting glomerular monoclonal
immunoglobulin G (
IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%).
RESULTS: The monoclonal
immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary
immune complex-mediated
glomerulonephritis and producing a diffuse endocapillary proliferative or
membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1kappa, one IgG1lambda, one IgG2lambda, four IgG3kappa, and one IgG3lambda). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted
immunoglobulin molecule. Tissue fixation of
complement was observed in 90% of cases, and 40% of patients had hypocomplementemia. Clinical presentations included
renal insufficiency in 80% (mean serum
creatinine 2.8 mg/dL, range 0.9 to 8.0),
proteinuria in 100% (mean urine
protein 5.8 g/day; range 1.9 to 13.0),
nephrotic syndrome in 44%, and microhematuria in 60%. A monoclonal
serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50% of cases (including three IgGkappa and two IgGlambda); however, no patient had clinical or laboratory features of type 1
cryoglobulinemia. No patient had overt myeloma or
lymphoma at presentation or over the course of follow-up (mean 12 months).
CONCLUSION: Glomerular deposition of monoclonal
IgG can produce a proliferative
glomerulonephritis that mimics
immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.