Abstract: SA-PO226
Unmasking the Invisible: A Puzzling Case of Type 1 Cryoglobulinemic Glomerulonephritis with Hidden Immunoglobulin Deposits
Session Information
- Onconephrology: Immunological Cross-Talk
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Hongboontry, Tinn, King Chulalongkorn Memorial Hospital, Bangkok, Bangkok, Thailand
- Ariyaskul, Darlene, King Chulalongkorn Memorial Hospital, Bangkok, Bangkok, Thailand
- Surintrspanont, Jerasit, King Chulalongkorn Memorial Hospital Department of Pathology, Bangkok, Thailand
- Kittanamongkolchai, Wonngarm, King Chulalongkorn Memorial Hospital, Bangkok, Bangkok, Thailand
Introduction
Monoclonal immunoglobulins (Ig) occasionally yield false negative results on standard immunofluorescence (IF). Identifying these Ig is vital for determining the patient's disease pathogenesis and therapeutic intervention.
Case Description
A 60-year-old female presented with fever, dysuria, and flank pain. She was diagnosed with E. coli pyelonephritis and received ceftriaxone. Her symptoms resolved after a week, but she developed oliguria without urinary tract obstruction seen on ultrasound. Her urine examination revealed dysmorphic red blood cells and urine protein creatinine index of 5.5 g/g. Lab tests showed low C3, C4 levels, detectable cryoglobulins, elevated ASO titer and anti-DNase B. Serum protein electrophoresis (SPEP) showed IgG lambda monoclonal protein. Considering the patient's history of HCV infection, mixed cryoglobulinemia was suspected. A renal biopsy demonstrated diffuse endocapillary proliferation and focal membranoproliferative glomerulonephritis (MPGN) pattern with focal wire loops and hyaline thrombi. IF stains revealed isolated granular staining for C3 in the mesangium and capillary loops. Electron microscopy showed electron dense deposits in the mesangium and subendothelium with vague microtubular structures (20–25 nm).
To differentiate GN with predominant C3 (post-infectious GN) from type I cryoglobulinemic GN with masked monotypic Ig deposits, paraffin IF with pronase digestion was performed. This method revealed the presence of IgG, lambda, C3, while kappa remained negative, leading to the final diagnosis of type I cryoglobulinemic GN.
Bone marrow biopsy showed a normocellular trilineage marrow. The reatment was switched to a bortezomib-based regimen. Later her urine output improved, and serum creatinine declined to 2.25 mg/dL. Subsequent SPEP detected no monoclonal protein.
Discussion
High suspicion is necessary to avoid misdiagnosis in this case. Positive ASO and anti-DNase B, coupled with C3 dominant GN on renal biopsy, could have been erroneously diagnosed as post-infectious GN. Our case highlights the importance of performing paraffin IF with pronase digestion to detect masked Ig. This is crucial for patients whose kidney biopsy shows C3 dominant GN or MPGN pattern with concurrent monoclonal gammopathy or microscopic characteristics of cryoglobulinemic GN.