Table 1.
Studies on the immune phenotype of patients with membranous nephropathy.
| Reference | Patients' characteristics (number) | Assay/biomarkers | Results |
|---|---|---|---|
| Ozaki et al. (89) | MN (30): - Untreated, - with Prednisolone, - incomplete remission, - complete remission |
Flow cytometry/ Helper, suppressor T cells | • Untreated nephrotic patients showed a significant decreased in suppressor T cell levels and a relative increase in helper T cells. • Prednisolone-treated patients showed an increased number of suppressor T cells. |
| Wang et al. (90) | MN (66): - No previous IS HC (40) |
Flow cytometry/ Treg, B and T cells | • Treg cells were decreased in MN patients. • B cells were increased in MN patients. T cells (CD4+/CD8+) were increased in MN patients. • No association between circulating B cells and disease activity. |
| Cagnoli et al. (91) | MN (27) - 12/27 nephrotic syndrome, - 6/27 isolated proteinuria, - 9/27 complete remission - No previous IS MCD (20) IgAN (12) HC (15) |
Indirect IF/ Total peripheral T cells, CD4+, and CD8+ T cells | • Patients with MN and nephrotic syndrome presented a CD4+/CD8+ ratio greater than the control group due to a reduction of CD8+ T cell subset. |
| Zucchelli et al. (92) | MN (39): - 23/39 were treated with methylprednisolone + chlorambucil - 16/39 not treated - Patients with serum creatinine >1.7 mg/dl were excluded HC (30) |
Indirect IF/ Total peripheral T cells (LEU4), helper T cells (LEU3a), cytotoxic T cells (LEU2a) | • Helper/cytotoxic T cell ratio was significantly higher at baseline in MN patients than the in controls due to a reduction of LEU2 cell subset. • Baseline helper/cytotoxic T cell ratio was significantly higher in patients achieving remission as compared to non-responder patients. |
| Taube et al. (93) | MN (21) MCD (11) FSGS (15) |
Suppressor cell function evaluation due to response to Concanavalin A | • Significant reduction in lymphocyte transformation in each group of patients as compared to the control group. • Suppressor cell function was decreased in each group of patients as compared to the control group. |
| Hirayama et al. (94) | MN (8): - Proteinuria ranging from 2 to 7 g/day - Creatinine clearance> 100 ml/min/1.73 m2 HC (23) |
Intracellular cytokine assay by flow cytometry/T-helper cells, Th1 and Th2 cytokines | • Percentages of IL-2+CD4+ T cells were significantly lower in MN patients than in the controls. • No differences in percentages of IFN-γ+ IL-4+CD4+ T cells were observed between different groups. • Percentages of IL-10+CD4+ T cells were significantly higher in MN patients than in the control group. |
| Masutani et al. (95) | MN (24) MCD (13) FSGS (12) HC (51) |
Intracellular cytokine assay by flow cytometry/ T-helper cells, Th1 and Th2 cytokines | • Percentages of IL-4 in MN patients were significantly higher than in the other groups. • Th1/Th2 ratio was significantly lower in MN patients than in the other groups. • Percentages of IL-4 correlated with the amount of proteinuria in MN patients. |
| Kuroki et al. (96) | MN (14) HC (14) |
Flow cytometry/ T cells, T-helper cells, T-cytotoxic cells, B cells Real-time PCR/ Th1 and Th2 cytokines |
• CD4/CD8 cell ratio was higher in MN patients than in the control group, although numbers of T and B cells were similar to the control group. • IL-10 and IL-13 mRNA expression levels was higher in MN patients. • IL-4 enhances in vitro production of IgG4 by B cells in MN. |
| Fervenza et al. (97) | MN (20) - Patients were all treated with Rituximab - Creatinine clearance ≥30 ml/min/1.73 m2 - Persistent proteinuria >5 g/24 h |
Flow cytometry/ T, B and NK cells | • After rituximab treatment, proteinuria decreased and creatinine clearance increased. • None of the T-reg subset analyses showed significant quantitative differences. • Baseline quantification of lymphocyte subpopulations did not predict response to rituximab therapy. |
| Roccatello et al. (98) | MN (17) - Patients were all treated with rituximab |
Flow cytometry/B, T, Treg cells ELISA assay/IL-35 and PLA2R antibodies |
• After rituximab treatment, proteinuria decreased and serum creatinine remained stable during the follow-up. • Treg percentages were significantly higher after treatment as compared to baseline. |
| Rosenzwajget al. (99) | MN (25): - 16/25 were treated with NIAT + rituximab - 9/25 were treated with NIAT alone HC (27) |
Flow cytometry/ B, T, NK, Treg, γδ-T cellsMultiplex to detect several cytokines/ chemokines | • Percentages of switched (IgD−CD27+) and non-switched (IgD+CD27+) memory B cells were higher in MN patients due to a higher percentage of naïve B cells at baseline. • Treg percentages were lower in MN patient at baseline. • After rituximab treatment, responder patients to treatment showed a significantly increased percentage of Treg cells than non-responders. |
FSGS, focal segmental glomerulosclerosis; IFN, interferon; HC, healthy controls; IL, interleukin; IF, immunofluorescence; IS, immunosuppression; MCD, minimal change disease; MN, membranous nephropathy; NIAT, nonimmunosuppressive antiproteinuric treatment; NK, natural killer; Treg, regulatory T cells.