PMC6682634_01
Patient clinical presentation. (A) Left picture shows the face of the patient with alopecia totalis, edema and Cushingoid facies due to prolonged steroid treatment. Right picture shows trachyonychia of the toenails. (B) Pedigree of the family showing two healthy non-consanguineous parents and the patient (arrow) with c.2611C>T mutation in NFKB2. Sanger tracings of each individual in the family are presented. (C) NK cell cytotoxic function measured by 51Cr release assay. Left graph shows antibody dependent cellular cytotoxicity (ADCC) measured against Raji B cell targets in in the presence (dashed line) and absence (solid line) of rituximab. Right shows natural cytotoxicity against K562 targets in the presence (dashed line) and absence (solid line) of IL-2 stimulation. Due to sample availability and transport limitations this demonstrates a single assay performed in triplicate. (D) Electron microscopy of renal biopsy showing pedicellar effacement and few mesangial deposits (E) Left picture shows a chest X ray and chest CT scan taken during the patient's final stage of disease showing multiple bilateral foci of alveolar compromise with extensive consolidation of bilateral basal lobes, superior left lobe and medial lobe. (F) Graphic representation showing variations in CMV titers in blood (in blue) and proteinuria (in orange), Black arrows indicate nephrotic syndrome (NS) reactivations. Immunosuppressive and antiviral treatments are indicated in colored boxes as they were administered during the course of disease.
fped-07-00303-g0001.jpg
PMC6682634_04_fped-07-00303-g0001.jpg
F1
Ultrastructural findings showed complete pedicellar effacement characteristic of minimal change nephropathy and no intracellular inclusions or antibody deposits were demonstrated on cytopathology (Figure 1D). Interestingly, elevations in CMV titers in blood seemed to precede nephrotic syndrome relapses and correlate with increases in proteinuria (Figure 1F). During this final end stage disease, she developed Pneumocytis jiroveci pneumonia and fungal lung infection (Figure 1E).
PMC6682634_02
Patient clinical presentation. (A) Left picture shows the face of the patient with alopecia totalis, edema and Cushingoid facies due to prolonged steroid treatment. Right picture shows trachyonychia of the toenails. (B) Pedigree of the family showing two healthy non-consanguineous parents and the patient (arrow) with c.2611C>T mutation in NFKB2. Sanger tracings of each individual in the family are presented. (C) NK cell cytotoxic function measured by 51Cr release assay. Left graph shows antibody dependent cellular cytotoxicity (ADCC) measured against Raji B cell targets in in the presence (dashed line) and absence (solid line) of rituximab. Right shows natural cytotoxicity against K562 targets in the presence (dashed line) and absence (solid line) of IL-2 stimulation. Due to sample availability and transport limitations this demonstrates a single assay performed in triplicate. (D) Electron microscopy of renal biopsy showing pedicellar effacement and few mesangial deposits (E) Left picture shows a chest X ray and chest CT scan taken during the patient's final stage of disease showing multiple bilateral foci of alveolar compromise with extensive consolidation of bilateral basal lobes, superior left lobe and medial lobe. (F) Graphic representation showing variations in CMV titers in blood (in blue) and proteinuria (in orange), Black arrows indicate nephrotic syndrome (NS) reactivations. Immunosuppressive and antiviral treatments are indicated in colored boxes as they were administered during the course of disease.
fped-07-00303-g0001.jpg
PMC6682634_04_fped-07-00303-g0001.jpg
F1
Ultrastructural findings showed complete pedicellar effacement characteristic of minimal change nephropathy and no intracellular inclusions or antibody deposits were demonstrated on cytopathology (Figure 1D). Interestingly, elevations in CMV titers in blood seemed to precede nephrotic syndrome relapses and correlate with increases in proteinuria (Figure 1F). During this final end stage disease, she developed Pneumocytis jiroveci pneumonia and fungal lung infection (Figure 1E).
PMC6682634_03
Patient clinical presentation. (A) Left picture shows the face of the patient with alopecia totalis, edema and Cushingoid facies due to prolonged steroid treatment. Right picture shows trachyonychia of the toenails. (B) Pedigree of the family showing two healthy non-consanguineous parents and the patient (arrow) with c.2611C>T mutation in NFKB2. Sanger tracings of each individual in the family are presented. (C) NK cell cytotoxic function measured by 51Cr release assay. Left graph shows antibody dependent cellular cytotoxicity (ADCC) measured against Raji B cell targets in in the presence (dashed line) and absence (solid line) of rituximab. Right shows natural cytotoxicity against K562 targets in the presence (dashed line) and absence (solid line) of IL-2 stimulation. Due to sample availability and transport limitations this demonstrates a single assay performed in triplicate. (D) Electron microscopy of renal biopsy showing pedicellar effacement and few mesangial deposits (E) Left picture shows a chest X ray and chest CT scan taken during the patient's final stage of disease showing multiple bilateral foci of alveolar compromise with extensive consolidation of bilateral basal lobes, superior left lobe and medial lobe. (F) Graphic representation showing variations in CMV titers in blood (in blue) and proteinuria (in orange), Black arrows indicate nephrotic syndrome (NS) reactivations. Immunosuppressive and antiviral treatments are indicated in colored boxes as they were administered during the course of disease.
fped-07-00303-g0001.jpg
PMC6682634_04_fped-07-00303-g0001.jpg
F1
Ultrastructural findings showed complete pedicellar effacement characteristic of minimal change nephropathy and no intracellular inclusions or antibody deposits were demonstrated on cytopathology (Figure 1D). Interestingly, elevations in CMV titers in blood seemed to precede nephrotic syndrome relapses and correlate with increases in proteinuria (Figure 1F). During this final end stage disease, she developed Pneumocytis jiroveci pneumonia and fungal lung infection (Figure 1E).
PMC6682634_04
Patient clinical presentation. (A) Left picture shows the face of the patient with alopecia totalis, edema and Cushingoid facies due to prolonged steroid treatment. Right picture shows trachyonychia of the toenails. (B) Pedigree of the family showing two healthy non-consanguineous parents and the patient (arrow) with c.2611C>T mutation in NFKB2. Sanger tracings of each individual in the family are presented. (C) NK cell cytotoxic function measured by 51Cr release assay. Left graph shows antibody dependent cellular cytotoxicity (ADCC) measured against Raji B cell targets in in the presence (dashed line) and absence (solid line) of rituximab. Right shows natural cytotoxicity against K562 targets in the presence (dashed line) and absence (solid line) of IL-2 stimulation. Due to sample availability and transport limitations this demonstrates a single assay performed in triplicate. (D) Electron microscopy of renal biopsy showing pedicellar effacement and few mesangial deposits (E) Left picture shows a chest X ray and chest CT scan taken during the patient's final stage of disease showing multiple bilateral foci of alveolar compromise with extensive consolidation of bilateral basal lobes, superior left lobe and medial lobe. (F) Graphic representation showing variations in CMV titers in blood (in blue) and proteinuria (in orange), Black arrows indicate nephrotic syndrome (NS) reactivations. Immunosuppressive and antiviral treatments are indicated in colored boxes as they were administered during the course of disease.
fped-07-00303-g0001.jpg
PMC6682634_04_fped-07-00303-g0001.jpg
F1
Ultrastructural findings showed complete pedicellar effacement characteristic of minimal change nephropathy and no intracellular inclusions or antibody deposits were demonstrated on cytopathology (Figure 1D). Interestingly, elevations in CMV titers in blood seemed to precede nephrotic syndrome relapses and correlate with increases in proteinuria (Figure 1F). During this final end stage disease, she developed Pneumocytis jiroveci pneumonia and fungal lung infection (Figure 1E).
PMC6682634_05
(A) Flow cytometry dot plots showing T cell memory subsets in total CD3+ T cells as well as in CD4+ and CD8+ subsets. (B) Flow cytometry dot plots showing patient and control NK CD56+ NK cells and gating on CD56Dim and CD56Bright NK cells. (C) 5 panels showing mean fluorescence intensity and percent of positive cells for different NK cell markers and receptors within CD56 Dim and CD56 Bright NK cells. Low percentages of cells compared to healthy donor are marked in red.
fped-07-00303-g0002.jpg
PMC6682634_05_fped-07-00303-g0002.jpg
F2
CD4+ and CD8+ T cell compartments was observed (Figure 2A). Comprehensive NK cell phenotyping was performed as previously described. NK cell numbers and the proportion of CD56bright and CD56dim NK cells were within normal limits and similar to a healthy donor control (Figure 2B). CD107a mobilization, and perforin levels were comparable to control (Figure 2C).
PMC6682634_06