Where is igg deposits in glomerulonephritis?
Demographics, clinical features and laboratory workups of 5 included cases were summarized in Table 1. Two patients have undergone native biopsy with an unequivocal diagnosis of MPGN while no clear diagnoses were made in the other 3 cases since no native biopsy have been performed. All renal allograft biopsies were indicative, including proteinuria (5 cases), elevated serum creatinine (Scr) (4 cases) and hematuria (5 cases). The time interval from transplant to PGNMID is generally short, ranging from 5 months to 19 months.
Laboratory work-ups indicated normal serum complement C3/C4 levels in all 4 cases tested. Nevertheless, urine C3 excretion was increased in all 2 cases measured. Serum light-chain levels varied in different patients. Laboratory testing for cryoglobulin, C3 nephritic factor, complement factor H, complement factor H antibody and HBV/HCV/HIV were all negative except in case 5 in which HCV was present. These tests help to exclude cryoglobulinemia, C3 glomerulopathy and immune-complex-mediated glomerulonephritis that commonly manifested as MPGN pattern histopathologically. Serum monoclonal protein spike as detected by electrophoresis was negative in all 4 cases tested and bone marrow aspirate examination was also negative for plasma cell dyscrasias in 3 performed cases.
Renal pathological findings of a total of 9 biopsies were summarized in Table 2.
Patient 1: Microscopic observation of the native kidney biopsy showed a classic MPGN pattern with mesangial proliferation leading to hypercellularity and glomerular tuft lobulation. Mesangial interposition resulting in the so-called characteristic “tram tracks” or “double contours” could also be frequently observed and validated by silver stain. Masson trichrome stain revealed intense fuchsinophilic immune-complexes in the mesangium and along the GBM. IF indicated intense IgG, C3 and C1q positivity in the mesangium and along the GBM with granular texture. Heavy-chain subclass analysis showed only IgG3 positivity with negativity for IgG1, IgG2 and IgG4. Light-chain IF demonstrated kappa positivity and lambda negativity. EM findings were congruent with IF with electron-dense deposits along the GBM and in the mesangium. PGNMID recurrence was documented with the allograft biopsy showed similar LM (Fig. 1a, b) and IF features (Fig. 1c-h) with the native kidney biopsy, even though fuchsinophilic deposits observed by Masson trichrome stain and EM (Fig. 1i) were less conspicuous and widespread.
Patient 2: Medical record documented the native kidney disease was MPGN, however, a detailed re-evaluation of the slides of the native kidney biopsy was unobtainable. In the 1st allograft biopsy, only mild mesangial proliferation were seen (Fig. 2a-b) with negative IF and EM (Fig. 2c). In the 2nd allograft biopsy that was performed 12 months later, LM also only revealed mild mesangial proliferation (Fig. 2d-e). Nevertheless, IF showed bright granular staining for IgG (subcalss IgG3) and kappa predominantly in the mesangium(Fig. 2f-h). IF staining for C3, C1q and IgA, IgM were all negative. EM revealed obviously electron-dense deposits mainly in the mesangium (Fig. 2i). A 3rd biopsy performed 36 months after the 2nd biopsy demonstrated MPGN pattern in LM (Fig. 2j-k). Crescents and moderate interstitial fibrosis and tubular atrophy were also seen. Fuchsinophilic immune-complex deposits can occasionally be seen in the mesangium. In addition to similar IF findings with the 2nd biopsy, positive staining for C1q was also present (Fig. 2l-o). EM (Fig. 2p) showed extensive electron-dense deposits in the subendothelium and mesangium.
Patient 3: This patient was complicated by acute antibody-mediated rejection as indicated by extensive peritubular capillaritis and extensive peritubular capillary C4d positive staining. LM showed diffuse proliferative glomerulonephritis. IF were typical of PGNMID with monoclonal IgG3 and lambda positivity. C3 and C1q staining were also positive. EM demonstrated extensive electron-dense deposits in the mesangium and in the subendothelial spaces. Subepithelial electron-dense deposits were also occasionally observed.
Patient 4: LM and IF features were similar to those found in patient 3. Nonetheless, EM showed diffuse electron-dense deposits along the GBM. Widespread foot process effacement was seen, which explained massive proteinuria in this patient.
Patient 5: The 1st allograft biopsy was noticeable for obvious fuchsinophilic immune-complexes in the mesangium. IF indicated monoclonality of IgG3. Tubulitis was also present, which was consistent with acute cellular rejection. In the 2nd allograft biopsy 28 months later, extensive MPGN-pattern was observed in the majority of glomeruli. Histological deterioration as indicated by increasing interstitial fibrosis, glomerular lobulation and widespread foot process effacement were observed.
Treatment regimens, treatment-related adverse events and follow-up results were summarized in Table 3. PGNMID was treated with plasma exchange in 2 patient (patient 1 and 5), rituximab in 1 patient (patient 2) and bortezomib in 3 cases (patient 3, 4 and 5). Patient 3 was also treated with pulse steroid for concomitant antibody-mediated rejection. Patient 5 was first treated with sofosbuvir and daclatasvir for HCV infection, then with pulse steroid since acute rejection was considered to be the main cause for Scr elevation. No serious treatment-related complications were observed except varicella infection in patient 4. Long-term follow-up in patient 2 and 3 showed worsening Scr, resulting in dialysis. Scr and proteinuria in patient 4 and 5 decreased and then stabilized. Patient 1 died of pulmonary infections at 13 months follow-up. After treating with bortezomib and plasma exchange, patient 5 experienced dramatically decreased proteinuria.
Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a condition where monoclonal immunoglobulins are deposited in the glomerulus.
