An Unusual Case of Seronegative Cryoglobulinemic Glomerulonephritis with Dominant Organized IgA Deposits Associated with Staphylococcal Infection: Casual or Causal Relationship?

Introduction: Cryoglobulinemia refers to the presence of cryoglobulins (CGs) in the serum, encompassing a group of diseases caused by the type of circulating GC. Cryoglobulinemic glomerulonephritis (CryoGN) is the principal manifestation of renal involvement. The diagnosis may be challenging because the hallmark of cryoglobulinemia is the detection of CG in the serum. However, cases of CryoGN without serological evidence of CGs are not uncommon in clinical practice, often diagnosed by anatomopathological findings in the renal biopsy. Case Presentation: We report the case of an 86-year-old male who developed renal impairment, nephritic syndrome, and nephrotic-range proteinuria, without serological evidence of CGs, associated with staphylococcal bacteremia without apparent focus. Renal biopsy and pathological examination showed a membranoproliferative glomerulonephritis pattern with CD61-negative pseudothrombi. Immunofluorescence microscopy showed atypical IgA-dominant deposits. Electron microscopy revealed amorphous subendothelial and mesangial deposits and organized electrodense deposits within capillary loops (pseudothrombi) with microtubular substructure measuring 20-40 nm in thickness. These findings were consistent with seronegative CryoGN and microtubular organized atypical IgA-dominant deposits. Discussion: In this report, we discuss the clinical, analytical, and histopathological findings of a rare case of CryoGN without serological evidence of CGs. Regarding the etiology that triggered the glomerular disease in our patient, we conducted an exhaustive study in order to determine the underlying cause of CryoGN. At the time of biopsy, the patient had an active staphylococcal bacteremia. There are reports that postulate that staphylococcal antigens drive activation of immune system and in consequence, could cause this rare form of IgA-dominant glomerulonephritis with cryoglobulinemic features. After ruling out other causes of cryoglobulinemia, we discuss a plausible causal relationship of the staphylococcal infection in the pathogenesis of CryoGN in our patient.