Clinicopathological characteristics of patients with IgAN and IgAVN and transplantation donors
The clinical features of our patients with IgAN and IgAVN and transplantation donors are shown in Table 1. Patients with IgAN and IgAVN were adults, except for 1 IgAN patient. The median ages of patients in the IgAN-I, IgAN-II, IgAVN-I, and IgAVN-II subgroups, and healthy donors were 42, 67, 71, 60, and 53 years, respectively. In the IgAN-I subgroup, all patients presented with chance proteinuria and/or hematuria, and 3 had hypertension. In the IgAN-II subgroup, all patients presented with progressive renal dysfunction and/or edema, and 3 had hypertension. In the IgAVN group, all patients presented with urinary abnormalities with progressive renal dysfunction and/or edema after the onset of purpura, and 4 had hypertension. In the IgAVN-II subgroup, 1 patient presented with arthralgia and another patient presented with abdominal pain.
Table 1
Clinical characteristics of patients with IgAN and IgAVN included in the present study and control subjects
| IgAN-I | IgAN-II | IgAVN-I | IgAVN-II | Controls |
Number of patients and controls | 6 | 6 | 6 | 6 | 5 |
Median age (years) (range) | 42 (16‒71) | 67 (22‒76) | 71 (36‒78) | 60 (34‒74) | 53 (45‒77) |
Male:female | 3:3 | 2:4 | 2:4 | 2:4 | 1:4 |
Chance proteinuria and/or hematuria, n | 6 | 0 | | | |
Urinary abnormalities after the onset of purpura, n | | | 6 | 6 | |
Progressive renal dysfunction, n | 1 | 3 | 0 | 1 | |
Edema, n | 0 | 5 | 0 | 2 | |
Hypertension, n | 3 | 3 | 1 | 3 | |
Purpura, n | | | 6 | 6 | |
Arthralgia, n | | | 0 | 1 | |
Abdominal pain, n | | | 0 | 1 | |
Median proteinuria (g/day or g/gCr) at biopsy (range) | 0.4 (0.1–2.8) | 5.9 (4.1‒10.0) | 3.6 (0.2‒7.9) | 2.0 (0.5‒6.4) | 0.7 (0.1‒0.9) |
Median serum albumin (g/dL) (range) | 4.0 (3.5‒4.7) | 2.5 (2.2‒2.8) | 3.5 (1.8‒4.3) | 3.6 (2.5‒3.9) | 4.3 (3.5‒4.5) |
Nephrotic syndrome, n | 0 | 6 | 1 | 2 | |
Median serum Cr (mg/dL) (range) | 0.89 (0.50‒1.85) | 1.13 (0.62‒2.07) | 0.79 (0.48‒1.18) | 0.76 (0.59‒2.10) | 0.67 (0.60‒0.90) |
Median eGFR (mL/min/1.73 m2) (range) | 77.8 (32.6‒109.3) | 55.6 (22.4‒73.6) | 66.0 (34.5‒98.4) | 59.2 (25.1‒92.8) | 72.1 (66.9‒81.6) |
Median serum IgA (mg/dL) (range) | 439 (213‒921) | 322 (189‒528) | 305 (254‒410) | 330 (214‒382) | |
Cr: creatinine; eGFR: estimated glomerular filtration rate; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis |
The median levels of proteinuria were ≥ 3.5 g/day or g/gCr in the IgAN-II and IgAVN-I subgroups. The median level of serum albumin was ≤ 3.0 g/dL in the IgAN-II subgroup. All patients in the IgAN-II subgroup developed NS. In the IgAVN group, 3 patients developed NS. The median levels of the estimated glomerular filtration rate were < 60 mL/min/1.73 m2 in the IgAN-II and IgAVN-II subgroups. The median levels of serum IgA were elevated in the IgAN and IgAVN subgroups.
The pathological features of our patients with IgAN and IgAVN are shown in Table 2. The median times from clinical presentation to biopsy in the IgAN-I, IgAN-II, IgAVN-I, and IgAVN-II subgroups were 20, 5, 2, and 4 months, respectively. Clinical presentations that prompted biopsy were chance proteinuria and/or hematuria in the IgAN-I subgroup, progressive renal dysfunction and/or edema in the IgAN-II subgroup, and urinary abnormalities after the onset of purpura in the IgAVN group. In the IgAVN group, 5 patients experienced the relapse of purpura following spontaneous improvements before biopsy.
Table 2
Pathological characteristics of patients with IgAN and IgAVN included in the present study and control subjects
| IgAN-I | IgAN-II | IgAVN-I | IgAVN-II |
Median time from presentation to biopsy (months) (range) | 20 (6–40) | 5 (0.5-9) | 2 (0.5–12) # | 4 (0.5–15) # |
Median % of global sclerotic glomeruli (range) | 9.7 (0-44.4) | 35.3 (2.9–47.1) | 7.8 (0–16.0) | 7.5 (2.5–23.8) |
Oxford classification, n | | | | |
M score | 1 M0, 5 M1 | 2 M0, 4 M1 | | |
E score | 3 E0, 3 E1 | 5 E0, 1 E1 | | |
S score | 3 S0, 3 S1 | 3 S0, 3 S1 | | |
T score | 4 T0, 2 T1 | 3 T0, 1 T1, 2 T2 | | |
C score | 2 C0, 4 C1 | 1 C0, 4 C1, 1 C2 | | |
ISKDC classification grade, n | | | 2 IIIa, 4 IIIb | 1 IIIa, 5 IIIb |
Median % of glomeruli with crescent formation (range) | | | 2.8 (0–8.0) | 29.2 (20.0-44.8) |
Glomerular deposition (IF intensities), n | | | | |
IgA | 5 (2+), 1 (3+) | 2 (+), 4 (2+) | 2 (+), 4 (2+) | 1 (+), 5 (2+) |
IgG | 3 (‒), 1 (±), 2 (+) | 3 (‒), 1 (±), 2 (+) | 3 (‒), 1 (±), 2 (+) | 4 (‒), 1 (±), 1 (+) |
IgM | 1 (‒), 3 (±), 2 (+) | 2 (‒), 2 (±), 2 (+) | 4 (‒), 1 (±), 1 (+) | 4 (‒), 1 (±), 1 (+) |
κ | 4 (+), 2 (2+) | 2 (±), 2 (+), 2 (2+) | 2 (±), 2 (+), 2 (2+) | 2 (‒), 3 (+), 1 (2+) |
λ | 4 (+), 2 (2+) | 1 (±), 2 (+), 3 (2+) | 6 (+) | 6 (+) |
C3 | 4 (+), 2 (2+) | 1 (‒), 1 (±), 1 (+), 3 (2+) | 1 (‒), 3 (+), 2 (2+) | 1 (‒), 1 (±), 2 (+), 2 (2+) |
C1q | 5 (‒), 1 (±) | 6 (‒) | 6 (‒) | 6 (‒) |
C: cellular or fibrocellular crescents; E: endocapillary hypercellularity; IF: immunofluorescence; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis; ISKDC: International Study of Kidney Disease in Children; M: mesangial hypercellularity; S: segmental glomerulosclerosis; T: tubular atrophy and interstitial fibrosis |
# 2 patients in the I subgroup and 3 in the II subgroup had experienced the relapse of purpura following spontaneous remission. In these patients, the durations from the last episode of purpura development to biopsy are described. |
The median percentages of global sclerotic glomeruli in the IgAN-I, IgAN-II, IgAVN-I, and IgAVN-II subgroups were 9.7, 35.3, 7.8, and 7.5%, respectively. M and S scores in the Oxford classification [1] were similar between the IgAN-I and -II subgroups. E1 lesions were observed in 3 patients in the IgAN-I subgroup and in 1 in the IgAN-II subgroup. In the IgAN-II subgroup, T2 and C2 lesions were detected in 2 patients and 1 patient, respectively. All IgAVN patients showed focal or diffuse proliferation with < 50% of glomeruli with crescent formation of grade IIIa or IIIb in the ISKDC system [3]. The median % of glomeruli with crescent formation in the IgAVN-I and -II subgroups were 2.8 and 29.2%, respectively. On immunofluorescence microscopy, glomerular IgA deposition was noted in all patients with IgAN and IgAVN, and the co-deposition of IgG and IgM was observed in some patients. Positive staining for Ig κ and λ light chains and complement C3 and negative staining for complement C1q were detected in most patients with IgAN and IgAVN.
The clinicopathological features of IgAN patients without and with NS included in the immunohistochemical study are shown in Supplementary Tables S1 and S2 (Additional file 1 and 2).
Comparative Proteomic Analysis
In our proteomic analysis of glomerular proteins extracted from the laser microdissected glomeruli of enrolled subjects (Additional file 3: Table S3), a principal component analysis revealed a clear separation between the IgAN and IgAVN groups and the control group and an overlapping distribution between the IgAN and IgAVN groups (Fig. 1).
We identified 859 proteins with high confidence (experimental Q < 0.01), and further selected 546 proteins that were matched with ≥ 2 peptides. Proteins that increased or decreased in the IgAN and IgAVN subgroups with medium or high confidence (adjusted P < 0.05 or < 0.01) are shown in Tables 3, 4, 5, 6, and 7.
Table 3
Accession ID NCBInr DB | Accession ID GenBank DB | Protein name | Sequence coverage (%) | Peptide match (n) | IgAN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) |
34527290 | AK130476.1 | Ig α1 HC C region | 20 | 9 | 100 ** | 100 ** | 100 ** | 100 ** |
87783 | | Ig α2 HC C region | 30 | 6 | 100 ** | 100 ** | 100 ** | 100 ** |
34527698 | AK130813.1 | Ig γ1 HC C region | 24 | 9 | 100 ** | 100 ** | 100 ** | 100 ** |
304562031 | | Ig γ2 HC V region | 19 | 2 | 100 ** | 100 ** | 100 ** | |
10334541 | AJ390237.1 | Ig γ3 HC C region | 21 | 6 | 0.52 (4.14) | 1.16 (47.59) | 0.60 (57.33) | 1.14 (44.04) |
953267710 | | Ig γ4 HC C region | 16 | 5 | 100 ** | 100 ** | 100 ** | |
304563964 | | Ig γ4 HC V region | 24 | 3 | | 100 ** | 100 ** | 100 ** |
15825712 | BAC54153.1 | Ig µ HC VC region | 13 | 2 | 100 ** | 100 ** | 100 ** | 100 ** |
21669411 | | Ig κ LC VJ region | 31 | 6 | 100 ** | 100 ** | 100 ** | 100 ** |
21669561 | | Ig λ LC VJ region | 27 | 5 | 100 ** | 100 ** | 100 ** | 100 ** |
114319027 | | Ig joining chain | 15 | 3 | 2.32 (71.68) | 3.50 (45.89) | 4.23 (16.85) | 2.54 (34.33) |
C: constant; DB: database; HC: heavy chain; Ig: immunoglobulin; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis; LC: light chain; NCBInr: National Center for Biotechnology information non-redundant; V: variable; VC: variable and constant; VJ: variable and joining |
**P < 0.01 |
Table 4
List of complements and complement-regulating proteins
Accession ID NCBInr DB | Accession ID GenBank DB | Protein name | Sequence coverage (%) | Peptide Match (n) | IgAN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) |
115298678 | | C3 | 17 | 25 | 6.75 * (114.91) | 5.35 * (107.18) | 4.86 (93.25) | 2.64 (92.76) |
443671 | | C4A | 4 | 4 | 4.51 (65.96) | 4.72 (89.78) | 3.12 (61.45) | 4.00 (72.75) |
953514538 | | C5 | 2 | 2 | 100 ** | 100 ** | 100 ** | 100 ** |
109731764 | | C8γ | 13 | 2 | 2.00 (46.48) | 2.19 (46.82) | 0.65 (3.71) | 1.08 (16.90) |
119576392 | | C9 | 14 | 8 | 16.72 ** (98.31) | 9.78 ** (113.13) | 7.45 * (89.20) | 4.24 (88.87) |
183763 | | CFHR1 | 32 | 8 | 9.66 * (78.53) | 5.58 * (111.92) | 3.00 (107.85) | 3.25 (84.79) |
767910533 | | CFHR5 | 4 | 2 | 100 ** | 100 ** | 100 ** | 100 ** |
13477169 | | Vitronectin | 15 | 7 | 3.82 (102.41) | 3.75 (110.86) | 2.84 (105.66) | 3.03 (109.83) |
578815184 | | Clusterin | 20 | 13 | 2.48 (87.08) | 2.41 (109.01) | 1.81 (84.97) | 1.57 (77.56) |
4502503 | | C4BPA | 4 | 2 | 1.71 (113.99) | 1.89 (83.17) | 0.80 (57.79) | 0.63 (75.75) |
809019 | X05309.13 | CR1 | 3 | 3 | 0.53 (115.68) | 0.27 (123.83) | 0.57 (86.45) | 0.50 (106.89) |
C4BPA: C4b-binding protein α chain; CFHR: complement factor H-related protein; CR1: complement receptor 1; DB: database; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis; NCBInr: National Center for Biotechnology information non-redundant |
*P < 0.05, **P < 0.01 |
Table 5
List of podocyte-associated proteins
Accession ID NCBInr DB | Accession ID GenBank DB | Protein name | Sequence coverage (%) | Peptide match (n) | IgAN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) |
4235275 | | Talin 1 | 9 | 18 | 100 ** | | 100 ** | 100 ** |
4758822 | | Nephrin | 4 | 5 | 1.01 (95.98) | 0.87 (59.76) | 0.82 (49.93) | 0.90 (20.54) |
7657615 | | Podocin | 6 | 2 | 2.64 (78.71) | 1.83 (87.04) | 3.10 (83.40) | 3.80 (70.67) |
1034591669 | | Zo-1 | 5 | 8 | 0.89 (81.11) | 0.70 (76.53) | 1.38 (86.88) | 1.03 (99.74) |
5453599 | | CapZA2 | 9 | 2 | 0.51 (19.82) | 0.63 (15.37) | 0.68 (5.62) | 0.81 (20.25) |
62414289 | | Vimentin | 79 | 56 | 0.98 (89.42) | 0.83 (102.95) | 1.15 (100.59) | 1.24 (95.28) |
578810794 | | Synaptopodin | 13 | 10 | 1.72 (61.40) | 1.04 (63.53) | 1.33 (59.27) | 1.55 (63.72) |
12025678 | | α-Actinin-4 | 50 | 38 | 1.42 (81.14) | 0.83 (92.02) | 1.26 (79.98) | 1.24 (87.68) |
12667788 | | Myosin-9 | 16 | 26 | 0.99 (79.27) | 0.82 (83.75) | 0.89 (86.32) | 0.90 (84.35) |
219520307 | | Podocalyxin | 9 | 5 | 2.25 (81.92) | 1.21 (81.52) | 2.40 (81.50) | 1.81 (81.90) |
119615053 | | Integrin α3 | 4 | 4 | 1.26 (69.82) | 0.80 (83.25) | 1.17 (70.16) | 1.15 (70.64) |
CapZA2: F-actin capping protein α2; DB: database; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis; NCBInr: National Center for Biotechnology information non-redundant; Zo-1: zonula occludens-1 |
**P < 0.01 |
Table 6
List of glomerular basement membrane proteins
Accession ID NCBInr DB | Accession ID GenBank DB | Protein name | Sequence coverage (%) | Peptide match (n) | IgAN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) |
125987809 | | COL4 α1 | 6 | 5 | 0.27 (87.87) | 0.28 (109.92) | 0.12 ** (53.43) | 0.60 (129.11) |
116256354 | | COL4 α2 | 7 | 9 | 2.14 (55.82) | 2.13 (77.60) | 1.40 (71.10) | 1.55 (49.45) |
119591260 | | COL4 α3 | 7 | 6 | 2.20 (108.21) | 0.82 (112.25) | 1.57 (113.08) | 1.71 (114.47) |
116256356 | | COL4 α4 | 4 | 4 | 1.50 (57.26) | 1.41 (76.00) | 1.14 (77.27) | 1.62 (58.07) |
1034673478 | | COL4 α5 | 4 | 4 | 2.02 (76.80) | 1.35 (72.18) | 1.48 (92.65) | 2.16 (80.63) |
20147503 | | Laminin α5 | 19 | 58 | 1.72 (111.36) | 2.25 (100.34) | 1.40 (108.82) | 1.85 (93.85) |
1103585 | | Laminin β2 | 28 | 44 | 1.27 (84.02) | 0.91 (83.36) | 1.06 (85.04) | 1.09 (85.79) |
145309326 | | Laminin γ1 | 24 | 32 | 1.32 (72.95) | 1.02 (78.48) | 1.07 (86.85) | 1.11 (81.63) |
115298674 | | Nidogen-1 | 19 | 24 | 2.10 (45.61) | 1.57 (81.36) | 1.87 (60.30) | 2.15 (46.04) |
530360311 | | Agrin | 27 | 40 | 0.99 (78.54) | 0.64 (82.89) | 0.60 (93.13) | 0.72 (82.41) |
11602963 | | HSPG perlecan | 17 | 54 | 1.31 (76.31) | 1.19 (81.45) | 1.08 (84.44) | 1.15 (73.35) |
34364820 | | Fibronectin | 22 | 38 | 2.42 (94.55) | 2.95 (100.41) | 2.59 (94.34) | 2.47 (97.14) |
COL4: type IV collagen; DB: database; HSPG: heparan sulfate proteoglycan; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis; NCBInr: National Center for Biotechnology information non-redundant |
**P < 0.01 |
Table 7
List of extracellular matrix-associated proteins
Accession ID NCBInr DB | Accession ID GenBank DB | Protein name | Sequence coverage (%) | Peptide match (n) | IgAN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-I (n = 6) / Control (n = 5) ratio (Ratio variability [%]) | IgAVN-II (n = 6) / Control (n = 5) ratio (Ratio variability [%]) |
4503689 | | Fibrinogen α | 14 | 11 | 3.42 (88.22) | 9.17 ** (92.08) | 6.42 (91.47) | 6.11 (82.12) |
70906435 | | Fibrinogen β | 10 | 4 | 41.83 ** (37.42) | 44.84 ** (56.21) | 54.46 ** (42.26) | 43.68 ** (52.45) |
182440 | | Fibrinogen γ | 10 | 3 | 100 ** | 100 ** | 100 ** | 100 ** |
193787687 | AK094581.1 | βIG-H3 | 5 | 3 | 5.50 (85.79) | 9.24 ** (56.45) | 8.15 * (43.46) | 5.09 (44.75) |
57546919 | | Hornerin | 24 | 23 | 0.13 * (111.3) | 0.20 ** (134.16) | 0.23 (105.85) | 0.11 ** (113.00) |
βIG-H3: transforming growth factor-β inducible gene-h3; DB: database; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis; NCBInr: National Center for Biotechnology information non-redundant |
*P < 0.05, **P < 0.01 |
Igs are summarized in Table 3. The Ig α1, α2, γ1, γ2, γ3, γ4, and µ heavy chains, Ig κ and λ light chains, and Ig joining chain (J chain) [16] were detected, while the polymeric Ig receptor/secretory component (pIgR/SC) [16] was not. Among these proteins, significantly higher levels of the Ig α1, α2, γ1, γ2, γ4, and µ heavy chains and Ig κ and λ light chains were noted in the IgAN and IgAVN subgroups than in the control group. The level of the Ig J chain was also higher (> 2.3 fold) in the IgAN and IgAVN subgroups than in the control group.
Complements and complement-regulating proteins are summarized in Table 4. Complements C3, C4A, C5, C8γ, and C9 were detected. Among them, the levels of C3, C4A, C5, and C9 were higher (> 2.6 fold) in the IgAN and IgAVN subgroups than in the control group. Complement factor H-related proteins (CFHR) 1 and 5, vitronectin, clusterin, the C4b-binding protein α chain, and complement receptor 1 (CR1) were also detected. Among them, the levels of CFHR1, CFHR5, and vitronectin were higher (> 2.8 fold) in the IgAN and IgAVN subgroups than in the control group, whereas those of CR1 were lower (< 0.6 fold) in the IgAN and IgAVN subgroups than in the control group.
Detected podocyte-associated proteins [17, 18], including talin 1 [19], nephrin, podocin, zonula occludens-1 (Zo-1), F-actin capping protein α2 (CapZA2) [20], vimentin [21], synaptopodin, α-actinin-4, myosin-9, podocalyxin, and integrin α3, are summarized in Table 5. Among them, talin 1 levels were significantly higher in the IgAN-I subgroup and IgAVN group than in the control group, but were not detected in the IgAN-II subgroup. Podocin levels were higher (> 2.6 fold) in the IgAN-I subgroup and IgAVN group than in the control group.
Detected GBM proteins [12, 22], including type IV collagen (COL4) α chains, laminin α, β, and γ chains, nidogen-1, agrin, heparan sulfate proteoglycan perlecan, and fibronectin, are summarized in Table 6. Among them, fibronectin levels were higher (> 2.4 fold) in the IgAN and IgAVN subgroups than in the control group, whereas COL4 α1 chain levels were lower (≤ 0.6 fold) in the IgAN and IgAVN subgroups than in the control group.
Detected ECM-associated proteins [12], including fibrinogen, transforming growth factor-β inducible gene-h3 (βIG-H3), and hornerin are summarized in Table 7. Among them, the levels of the fibrinogen α, β, and γ chains and βIG-H3 were higher (> 3.4 fold) in the IgAN and IgAVN subgroups than in the control group, whereas those of hornerin were lower (< 0.3).
Table 8 summarizes proteins with abundance that significantly differed between the IgAN and IgAVN groups, the IgAN-I and -II subgroups, and the IgAVN-I and -II subgroups. Significantly different levels of C9, CFHR1, podocin, Zo-1, CapZA2, and vimentin were observed between the IgAN and IgAVN groups. Furthermore, the levels of CR1, podocin, synaptopodin, α-actinin-4, podocalyxin, COL4 α5 chain, and laminin β2 chain significantly differed between the IgAN-I and -II subgroups.
Table 8
List of proteins with abundance that significantly differed between groups
Accession ID | Protein name | IgAN total vs. IgAVN total | | IgAN-I vs. IgAN-II | | IgAVN-I vs. IgAVN-II |
NCBInr DB | | Fold change | P value | | Fold change | P value | | Fold change | P value |
119576392 | C9 | 2.26 | 0.043 * | | 1.82 | 0.228 | | 1.75 | 0.203 |
183763 | CFHR1 | 3.48 | 0.028 * | | 0.79 | 0.689 | | 1.07 | 0.898 |
809019 | CR1 | 0.68 | 0.273 | | 7.92 | 0.002 ** | | 0.91 | 0.838 |
7657615 | Podocin | 0.63 | 0.007 ** | | 2.04 | 0.017 * | | 1.08 | 0.618 |
1034591669 | Zo-1 | 0.43 | 0.001 ** | | 1.91 | 0.064 | | 0.99 | 0.984 |
5453599 | CapZA2 | 0.64 | 0.003 ** | | 1.26 | 0.464 | | 0.85 | 0.130 |
62414289 | Vimentin | 0.74 | 0.003 ** | | 1.19 | 0.367 | | 0.98 | 0.815 |
578810794 | Synaptopodin | 0.82 | 0.278 | | 2.42 | 0.009 ** | | 0.97 | 0.833 |
12025678 | α-Actinin-4 | 0.86 | 0.264 | | 1.59 | 0.027 * | | 0.96 | 0.775 |
219520307 | Podocalyxin | 0.82 | 0.300 | | 2.36 | 0.001 ** | | 1.22 | 0.432 |
1034673478 | COL4 α5 | 0.88 | 0.490 | | 1.87 | 0.034 * | | 0.86 | 0.483 |
1103585 | Laminin β2 | 0.93 | 0.569 | | 1.54 | 0.032 * | | 0.98 | 0.911 |
CapZA2: F-actin capping protein α2; CFHR: complement factor H-related protein; COL4: type IV collagen; CR1: complement receptor 1; DB: database; IgAN: IgA nephropathy; IgAVN: IgA vasculitis with nephritis; NCBInr: National Center for Biotechnology information non-redundant; Zo-1: zonula occludens-1 |
*P < 0.05, **P < 0.01 |
Immunohistochemistry
In IgAN patients without NS, glomerular talin 1 staining was observed in podocytes and parietal podocytes, along capillary walls, and in the probable cell debris of detached podocytes within the urinary space (Fig. 2a). Talin 1 staining was also detected in proximal tubular epithelial cells, suggesting the reabsorption of talin 1 derived from detached podocytes (Fig. 2a). A reduced number of podocytes, associated with severe mesangial expansion, was observed in IgAN patients with NS (Fig. 2b). Glomerular staining for talin 1 was less intense than in IgAN patients without NS (Fig. 2b).