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pmid:33568149

Isotypes of autoantibodies against novel differential 4-hydroxy-2-nonenal-modified peptide adducts in serum is associated with rheumatoid arthritis in Taiwanese women.

Kai-Leun Tsai · Che-Chang Chang · Yu-Sheng Chang · Yi-Ying Lu · I-Jung Tsai · Jin-Hua Chen · Sheng-Hong Lin · Chih-Chun Tai · Yi-Fang Lin · Hui-Wen Chang · Ching-Yu Lin · Emily Chia-Yu Su

BMC medical informatics and decision making · 2021 doi:10.1186/s12911-020-01380-y

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33568149
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science-record
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sha256:26a89902300d93a17f1e2b95c64a758884753aa9981fe51f7072c90831e8528f
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T15:41:24Z
updated_at
2026-11-01T22:03:05Z
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title
Isotypes of autoantibodies against novel differential 4-hydroxy-2-nonenal-modified peptide adducts in serum is associated with rheumatoid arthritis in Taiwanese women.
doi
10.1186/s12911-020-01380-y
pmid
33568149
authors array · 12 items
[0]
Kai-Leun Tsai
[1]
Che-Chang Chang
[2]
Yu-Sheng Chang
[3]
Yi-Ying Lu
[4]
I-Jung Tsai
[5]
Jin-Hua Chen
[6]
Sheng-Hong Lin
[7]
Chih-Chun Tai
[8]
Yi-Fang Lin
[9]
Hui-Wen Chang
[10]
Ching-Yu Lin
[11]
Emily Chia-Yu Su
journal
BMC medical informatics and decision making
year
2021
abstract
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients. METHODS: Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Four novel differential HNE-modified peptide adducts, complement factor H (CFAH)1211-1230, haptoglobin (HPT)78-108, immunoglobulin (Ig) kappa chain C region (IGKC)2-19, and prothrombin (THRB)328-345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546) from RA patients vs. HCs. Further, we determined serum protein levels of CFAH, HPT, IGKC and THRB, HNE-protein adducts, and autoantibodies against unmodified and HNE-modified peptides. Significant correlations and odds ratios (ORs) were calculated. RESULTS: Levels of HPT in RA patients were greatly higher than the levels in HCs. Levels of HNE-protein adducts and autoantibodies in RA patients were significantly greater than those of HCs. IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgM anti-IGKC2-19 HNE may be considered as diagnostic biomarkers for RA. Importantly, elevated levels of IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 were positively correlated with the disease activity score in 28 joints for C-reactive protein (DAS28-CRP). Further, the ORs of RA development through IgM anti-HPT78-108 HNE (OR 5.235, p < 0.001), IgM anti-IGKC2-19 (OR 12.655, p < 0.001), and IgG anti-THRB328-345 (OR 5.761, p < 0.001) showed an increased risk. Lastly, we incorporated three machine learning models to differentiate RA from HC and OA, and performed feature selection to determine discriminative features. Experimental results showed that our proposed method achieved an area under the receiver operating characteristic curve of 0.92, which demonstrated that our selected autoantibodies combined with machine learning can efficiently detect RA. CONCLUSIONS: This study discovered that some IgG- and IgM-NAAs and anti-HNE M-NAAs may be correlated with inflammation and disease activity in RA. Moreover, our findings suggested that IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 may play heavy roles in RA development.
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As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs
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methodological
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null
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sections[15] "Associations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with RA patients compared to HCs" paragraph 2
quote
As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs
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complete
[1] object · 6 fields
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claim-data-access
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The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.
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sections[25] "Availability of data and materials" paragraph 2
quote
The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.
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The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.
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The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.
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Human Rheumatoid Arthritis LC-MSMS
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Differential 4-hydroxy-2-nonenal (HNE)-modified peptide adducts in rheumatoid arthritis (RA) patients compared to healthy controls (HCs)
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pmcid
PMC7874460
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13
section_title
Measuring autoantibodies against unmodified and HNE-modified peptides
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Table 1
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Differential 4-hydroxy-2-nonenal (HNE)-modified peptide adducts in rheumatoid arthritis (RA) patients compared to healthy controls (HCs)
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[0] array · 8 items
[0]
Proteina
[1]
Modified peptideb
[2]
Positionc
[3]
Obs.d
[4]
Calc.e
[5]
dMf
[6]
dMg
[7]
Sequence foundwith modifications
[1] array · 2 items
[0]
HC
[1]
RA
[2] array · 9 items
[0]
CFAH
[1]
SHTLRTTCWDGKLEYPTCAK(+ 158)
[2]
1211–1230
[3]
858.439
[4]
858.435
[5]
0.0041
[6]
5.4
[7]
−
[8]
+
[3] array · 8 items
[0]
HRTGDEITYQCRNGFYPATRGNTAK(+ 138)
[1]
284–308
[2]
749.370
[3]
749.372
[4]
− 0.0018
[5]
−1.8
[6]
+
[7]
−
[4] array · 9 items
[0]
HPT
[1]
AVGDKLPECEADDGC(+ 158)PKPPEIAHGYVEHSVR
[2]
78–108
[3]
869.925
[4]
869.927
[5]
− 0.0017
[6]
−1.3
[7]
−
[8]
+
[5] array · 8 items
[0]
ILGGHLDA(+ 156)K
[1]
162–170
[2]
540.329
[3]
540.327
[4]
0.0028
[5]
6.1
[6]
+
[7]
−
[6] array · 9 items
[0]
IGKC
[1]
TVAA(+ 156)PSVFIFPPSDEQLK
[2]
2–19
[3]
701.384
[4]
701.386
[5]
− 0.0018
[6]
−1.7
[7]
−
[8]
+
[7] array · 8 items
[0]
TVA(+ 156)APSVFIFPPSDEQLK
[1]
2–19
[2]
1051.582
[3]
1051.575
[4]
0.0070
[5]
7.1
[6]
+
[7]
+
[8] array · 8 items
[0]
VYACEVTHQ(+ 158)GLSSPVTKSFNR
[1]
83–103
[2]
862.780
[3]
862.785
[4]
− 0.0044
[5]
−4.5
[6]
+
[7]
−
[9] array · 9 items
[0]
THRB
[1]
TFGSGEADCGLRPLFEK(+ 156)K
[2]
328–345
[3]
1056.036
[4]
1056.046
[5]
− 0.0107
[6]
−9.6
[7]
−
[8]
+
[10] array · 8 items
[0]
TFGSGEADC(+ 140)GLRPL(+ 156)FEK
[1]
328–344
[2]
708.376
[3]
708.375
[4]
0.0009
[5]
2.1
[6]
+
[7]
−
locator
section[13]/table-wrap[1]#Tab1
[3] object · 16 fields
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Comparisons of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides in rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients compared to healthy controls (HCs)
structure object · 5 fields
pmcid
PMC7874460
section_index
13
section_title
Measuring autoantibodies against unmodified and HNE-modified peptides
row_count
34
column_count
8
table object · 8 fields
label
Table 2
caption
Comparisons of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides in rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients compared to healthy controls (HCs)
rows array · 34 items
[0] array · 4 items
[0]
Peptides
[1]
RA vs. HC
[2]
OA versus HC
[3]
p value a
[1] array · 6 items
[0]
AUC (95%CI)
[1]
Sensitivity (95%CI)
[2]
Specificity (95%CI)
[3]
AUC (95%CI)
[4]
Sensitivity (95%CI)
[5]
Specificity (95%CI)
[2] array · 8 items
[0]
IgG anti-CFAH1121−1230
[1]
0.66 (0.57–0.76)
[2]
63.3% (49.9–75.4)
[3]
51.7% (38.4–64.8)
[4]
0.58 (0.46–0.70)
[5]
60.0% (42.1–76.1)
[6]
60.0% (46.5–72.4)
[7]
0.6844
[3] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.24
[3]
[4]
[5]
< 0.21
[6]
[7]
[4] array · 8 items
[0]
IgG anti-CFAH1121−1230 HNE
[1]
0.71 (0.62–0.80)
[2]
76.7% (64.0–86.6)
[3]
55.0% (41.6–67.9)
[4]
0.52 (0.40–0.64)
[5]
51.4% (34.0–68.6)
[6]
50.0% (36.8–63.2)
[7]
0.0135
[5] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.21
[3]
[4]
[5]
< 0.20
[6]
[7]
[6] array · 8 items
[0]
IgM anti-CFAH1121−1230
[1]
0.68 (0.59–0.78)
[2]
81.7% (69.6–90.5)
[3]
53.3% (40.0–66.3)
[4]
0.68 (0.58–0.79)
[5]
77.1% (59.9–89.6)
[6]
60.0% (46.5–72.4)
[7]
0.4816
[7] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.58
[3]
[4]
[5]
> 0.63
[6]
[7]
[8] array · 8 items
[0]
IgM anti-CFAH1121−1230 HNE
[1]
0.70 (0.61–0.79)
[2]
85.0% (73.4–92.9)
[3]
41.7% (29.1–55.1)
[4]
0.59 (0.47–0.71)
[5]
80.0% (63.1–91.6)
[6]
36.7% (24.6–50.1)
[7]
0.0421
[9] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.24
[3]
[4]
[5]
> 0.23
[6]
[7]
[10] array · 8 items
[0]
IgG anti-HPT78−108
[1]
0.67 (0.58–0.77)
[2]
71.7% (58.6–82.6)
[3]
55.0% (41.6–67.9)
[4]
0.53 (0.41–0.65)
[5]
51.4% (34.0–68.6)
[6]
46.7% (33.7–60.0)
[7]
0.3711
[11] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.64
[3]
[4]
[5]
< 0.64
[6]
[7]
[12] array · 8 items
[0]
IgG anti-HPT78−108 HNE
[1]
0.66 (0.57–0.76)
[2]
71.7% (58.6–82.6)
[3]
48.3% (35.2–61.6)
[4]
0.58 (0.46–0.70)
[5]
62.9% (44.9–78.5)
[6]
55.0% (41.6–67.9)
[7]
0.8974
[13] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.25
[3]
[4]
[5]
< 0.25
[6]
[7]
[14] array · 8 items
[0]
IgM anti-HPT78−108
[1]
0.67 (0.57–0.77)
[2]
71.7% (58.6–82.6)
[3]
56.7% (43.2–69.4)
[4]
0.53(0.40–0.66)
[5]
51.4%(33.9–68.6)
[6]
50.0%(36.8– 63.2)
[7]
0.2823
[15] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.30
[3]
[4]
[5]
< 0.29
[6]
[7]
[16] array · 8 items
[0]
IgM anti-HPT78−108 HNE
[1]
0.89 (0.80–0.93)
[2]
86.7% (75.4–94.1)
[3]
66.7% (53.3–78.3)
[4]
0.58 (0.46–0.69)
[5]
65.7% (47.8–80.9)
[6]
55.0% (41.6–67.9)
[7]
< 0.0001
[17] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.20
[3]
[4]
[5]
> 0.16
[6]
[7]
[18] array · 8 items
[0]
IgG anti-IGKC2−19
[1]
0.72 (0.62–0.81)
[2]
80.0% (67.7–89.2)
[3]
60.0% (46.5–72.4)
[4]
0.59 (0.47–0.70)
[5]
65.7% (47.8–80.9)
[6]
53.3% (40.0–66.3)
[7]
0.1471
[19] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.41
[3]
[4]
[5]
> 0.37
[6]
[7]
[20] array · 8 items
[0]
IgG anti-IGKC2−19 HNE
[1]
0.70 (0.61–0.79)
[2]
78.3% (65.8–87.9)
[3]
56.7% (43.2–69.4)
[4]
0.55 (0.43–0.67)
[5]
65.7% (47.9–80.9)
[6]
50.0% (36.8–63.2)
[7]
0.0917
[21] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.45
[3]
[4]
[5]
> 0.39
[6]
[7]
[22] array · 8 items
[0]
IgM anti-IGKC2−19
[1]
0.83 (0.75–0.90)
[2]
81.7% (69.6–90.5)
[3]
60.0% (46.5–72.4)
[4]
0.56 (0.44–0.68)
[5]
57.1% (39.4–73.7)
[6]
50.0% (36.8–63.2)
[7]
< 0.0001
[23] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.61
[3]
[4]
[5]
> 0.53
[6]
[7]
[24] array · 8 items
[0]
IgM anti-IGKC2−19 HNE
[1]
0.86 (0.79–0.93)
[2]
83.3% (71.5–91.7)
[3]
66.7% (53.3–78.3)
[4]
0.58 (0.46–0.70)
[5]
68.6% (50.7–83.2)
[6]
51.7% (38.4–64.8)
[7]
< 0.0001
[25] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.37
[3]
[4]
[5]
> 0.32
[6]
[7]
[26] array · 8 items
[0]
IgG anti-THRB328−345
[1]
0.70 (0.61–0.79)
[2]
66.7% (53.3–78.3)
[3]
53.3% (40.0–66.3)
[4]
0.53 (0.42–0.65)
[5]
62.9% (44.9–78.5)
[6]
48.3% (35.2–61.6)
[7]
0.0086
[27] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.20
[3]
[4]
[5]
> 0.19
[6]
[7]
[28] array · 8 items
[0]
IgG anti-THRB328−345 HNE
[1]
0.75 (0.67–0.84)
[2]
80.0% (67.7–89.2)
[3]
53.3% (40.0–66.3)
[4]
0.60 (0.48–0.71)
[5]
68.6% (50.7–83.2)
[6]
50.0% (36.8–63.2)
[7]
0.0087
[29] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.32
[3]
[4]
[5]
> 0.31
[6]
[7]
[30] array · 8 items
[0]
IgM anti-THRB328−345
[1]
0.63 (0.53–0.73)
[2]
63.3% (50.0–75.4)
[3]
53.3% (40.0–66.3)
[4]
0.56 (0.44–0.68)
[5]
60.0% (42.1–76.1)
[6]
53.3% (40.0–66.3)
[7]
0.5845
[31] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.61
[3]
[4]
[5]
> 0.60
[6]
[7]
[32] array · 8 items
[0]
IgM anti-THRB328−345 HNE
[1]
0.78 (0.69–0.86)
[2]
76.7% (64.0–86.6)
[3]
71.7% (58.6–82.6)
[4]
0.56 (0.44–0.68)
[5]
65.7% (47.8–80.9)
[6]
46.7% (33.7–60.0)
[7]
0.0001
[33] array · 8 items
[0]
Cutoff (OD450)
[1]
[2]
> 0.64
[3]
[4]
[5]
> 0.52
[6]
[7]
locator
section[13]/table-wrap[2]#Tab2
[4] object · 16 fields
id
asset:table:pmid:33568149:3
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:fc8ce78dc9008b66d2779170f9ee12b3a82131de07dfc5cf2ebe99ea2c736523
bytes
2775
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[14]/table-wrap[1]#Tab3
version
null
note
Correlations between autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides and clinical variables in rheumatoid arthritis (RA) patients (n = 60)
structure object · 5 fields
pmcid
PMC7874460
section_index
14
section_title
Correlations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with clinical variables in RA patients
row_count
18
column_count
13
table object · 8 fields
label
Table 3
caption
Correlations between autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides and clinical variables in rheumatoid arthritis (RA) patients (n = 60)
rows array · 18 items
[0] array · 7 items
[0]
[1]
DAS28
[2]
RF
[3]
Anti-CCP
[4]
CRP
[5]
ESR
[6]
HNE adduct
[1] array · 12 items
[0]
r
[1]
p value
[2]
r
[3]
p value
[4]
r
[5]
p value
[6]
r
[7]
p value
[8]
r
[9]
p value
[10]
r
[11]
p value
[2] array · 13 items
[0]
IgG anti-CFAH1121−1230
[1]
0.1580
[2]
0.2279
[3]
0.0968
[4]
0.4696
[5]
0.0108
[6]
0.9347
[7]
0.0229
[8]
0.8659
[9]
0.2076
[10]
0.1115
[11]
− 0.009
[12]
0.9458
[3] array · 13 items
[0]
IgG anti-CFAH1121−1230 HNE
[1]
− 0.0441
[2]
0.7379
[3]
− 0.0035
[4]
0.9794
[5]
− 0.0359
[6]
0.7852
[7]
− 0.1446
[8]
0.2831
[9]
0.1359
[10]
0.3006
[11]
− 0.0082
[12]
0.9501
[4] array · 13 items
[0]
IgM anti-CFAH1121−1230
[1]
0.0424
[2]
0.7477
[3]
0.0626
[4]
0.6406
[5]
0.2100
[6]
0.1073
[7]
− 0.0164
[8]
0.9036
[9]
0.0756
[10]
0.5658
[11]
− 0.0503
[12]
0.7026
[5] array · 13 items
[0]
IgM anti-CFAH1121−1230HNE
[1]
0.0377
[2]
0.7748
[3]
0.0435
[4]
0.746
[5]
0.2192
[6]
0.0924
[7]
− 0.0821
[8]
0.5435
[9]
0.1343
[10]
0.3063
[11]
0.0302
[12]
0.8186
[6] array · 13 items
[0]
IgG anti-HPT78−108
[1]
0.0929
[2]
0.4804
[3]
0.1386
[4]
0.2996
[5]
0.0659
[6]
0.6169
[7]
0.1138
[8]
0.3994
[9]
0.1695
[10]
0.1954
[11]
0.0754
[12]
0.5670
[7] array · 13 items
[0]
IgG anti-HPT78−108 HNE
[1]
− 0.0266
[2]
0.8400
[3]
0.0195
[4]
0.8848
[5]
0.2782
[6]
0.0314
[7]
0.1081
[8]
0.4236
[9]
0.1346
[10]
0.3052
[11]
− 0.0593
[12]
0.6529
[8] array · 13 items
[0]
IgM anti-HPT78−108
[1]
− 0.0171
[2]
0.8969
[3]
0.1711
[4]
0.1992
[5]
0.0877
[6]
0.5051
[7]
− 0.0591
[8]
0.6623
[9]
0.0074
[10]
0.9555
[11]
− 0.0453
[12]
0.7310
[9] array · 13 items
[0]
IgM anti-HPT78−108 HNE
[1]
0.2703
[2]
0.0367
[3]
0.6140
[4]
< 0.0001
[5]
0.0294
[6]
0.8238
[7]
0.1236
[8]
0.3596
[9]
0.2180
[10]
0.0943
[11]
0.1836
[12]
0.1603
[10] array · 13 items
[0]
IgG anti-IGKC2−19
[1]
− 0.3538
[2]
0.0056
[3]
− 0.1144
[4]
0.3926
[5]
− 0.0023
[6]
0.9862
[7]
− 0.1061
[8]
0.4320
[9]
− 0.123
[10]
0.3597
[11]
0.2097
[12]
0.1078
[11] array · 13 items
[0]
IgG anti-IGKC2−19 HNE
[1]
0.6023
[2]
− 0.3432
[3]
0.0073
[4]
− 0.1997
[5]
0.1328
[6]
0.1253
[7]
0.3399
[8]
− 0.0524
[9]
0.6986
[10]
− 0.0328
[11]
0.8035
[12]
0.0686
[12] array · 13 items
[0]
IgM anti-IGKC2−19
[1]
0.2816
[2]
0.0293
[3]
0.5674
[4]
< 0.0001
[5]
− 0.0588
[6]
0.6553
[7]
0.0511
[8]
0.7059
[9]
0.2692
[10]
0.0376
[11]
0.2667
[12]
0.0394
[13] array · 13 items
[0]
IgM anti-IGKC2−19 HNE
[1]
0.2487
[2]
0.0553
[3]
0.5404
[4]
< 0.0001
[5]
0.2439
[6]
0.0604
[7]
0.0429
[8]
0.7512
[9]
0.2985
[10]
0.0205
[11]
0.2709
[12]
0.0363
[14] array · 13 items
[0]
IgG anti-THRB328−345
[1]
0.2703
[2]
0.0367
[3]
0.6140
[4]
< 0.0001
[5]
0.2439
[6]
0.0604
[7]
0.1236
[8]
0.3596
[9]
0.218
[10]
0.0943
[11]
0.1836
[12]
0.1603
[15] array · 13 items
[0]
IgG anti-THRB328−345 HINE
[1]
0.1274
[2]
0.3320
[3]
0.3072
[4]
0.019
[5]
0.2549
[6]
0.0494
[7]
− 0.0575
[8]
0.6712
[9]
0.1341
[10]
0.307
[11]
0.0170
[12]
0.8972
[16] array · 13 items
[0]
IgM anti-THRB328−345
[1]
− 0.0637
[2]
0.6290
[3]
0.2207
[4]
0.096
[5]
− 0.0365
[6]
0.7821
[7]
− 0.0292
[8]
0.8293
[9]
− 0.1513
[10]
0.2473
[11]
− 0.2796
[12]
0.0305
[17] array · 13 items
[0]
IgM anti-THRB328−345 HNE
[1]
0.0818
[2]
0.5345
[3]
0.2845
[4]
0.0304
[5]
− 0.0438
[6]
0.7397
[7]
0.081
[8]
0.549
[9]
0.2597
[10]
0.0451
[11]
0.1036
[12]
0.4310
locator
section[14]/table-wrap[1]#Tab3
[5] object · 16 fields
id
asset:table:pmid:33568149:4
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:7745041f544f84fa98b9d183d75a9b5c48f42ba2866ea9a36a83b34c13b7b7bd
bytes
2756
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[15]/table-wrap[1]#Tab4
version
null
note
Associations of 4-hydroxy-2-nonenal (HNE)-protein adducts and autoantibody isotypes against unmodified and HNE-modified peptides in rheumatoid arthritis (RA) patients vs. healthy controls (HCs)
structure object · 5 fields
pmcid
PMC7874460
section_index
15
section_title
Associations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with RA patients compared to HCs
row_count
36
column_count
8
table object · 8 fields
label
Table 4
caption
Associations of 4-hydroxy-2-nonenal (HNE)-protein adducts and autoantibody isotypes against unmodified and HNE-modified peptides in rheumatoid arthritis (RA) patients vs. healthy controls (HCs)
rows array · 36 items
[0] array · 8 items
[0]
Risk factor
[1]
[2]
Cutoff
[3]
HC
[4]
RA
[5]
Age-adjusted logistic regression modela
[6]
p value
[7]
Power
[1] array · 3 items
[0]
(n)
[1]
(n)
[2]
OR (95% CI)
[2] array · 8 items
[0]
HNE-protein adduct
[1]
<
[2]
2.386
[3]
26
[4]
24
[5]
1.0 (Ref)
[6]
0.014
[7]
0.743
[3] array · 7 items
[0]
≥
[1]
2.386
[2]
34
[3]
71
[4]
2.413 (1.193, 4.880)
[5]
[6]
[4] array · 8 items
[0]
IgG anti-CFAH1121−1230
[1]
<
[2]
0.175
[3]
14
[4]
8
[5]
1.0 (Ref)
[6]
0.013
[7]
0.874
[5] array · 7 items
[0]
≥
[1]
0.175
[2]
46
[3]
87
[4]
3.293 (1.286, 8.431)
[5]
[6]
[6] array · 8 items
[0]
IgG anti-CFAH1121−1230 HNE
[1]
<
[2]
0.263
[3]
46
[4]
51
[5]
1.0 (Ref)
[6]
0.005
[7]
0.870
[7] array · 7 items
[0]
≥
[1]
0.263
[2]
14
[3]
44
[4]
2.808 (1.363, 5.785)
[5]
[6]
[8] array · 8 items
[0]
IgM anti-CFAH1121−1230
[1]
<
[2]
0.609
[3]
35
[4]
20
[5]
1.0 (Ref)
[6]
< 0.001
[7]
0.979
[9] array · 7 items
[0]
≥
[1]
0.609
[2]
25
[3]
75
[4]
5.204 (2.550, 10.617)
[5]
[6]
[10] array · 8 items
[0]
IgM anti-CFAH1121−1230 HNE
[1]
<
[2]
0.333
[3]
39
[4]
39
[5]
1.0 (Ref)
[6]
0.004
[7]
0.838
[11] array · 7 items
[0]
≥
[1]
0.333
[2]
21
[3]
56
[4]
2.700 (1.378, 5.289)
[5]
[6]
[12] array · 8 items
[0]
IgG anti-HPT78−108
[1]
<
[2]
0.662
[3]
35
[4]
37
[5]
1.0 (Ref)
[6]
0.024
[7]
0.645
[13] array · 7 items
[0]
≥
[1]
0.662
[2]
25
[3]
58
[4]
2.156 (1.108, 4.193)
[5]
[6]
[14] array · 8 items
[0]
IgG anti-HPT78−108 HNE
[1]
<
[2]
0.307
[3]
41
[4]
51
[5]
1.0 (Ref)
[6]
0.094
[7]
0.455
[15] array · 7 items
[0]
≥
[1]
0.307
[2]
19
[3]
44
[4]
1.821 (0.904, 3.672)
[5]
[6]
[16] array · 8 items
[0]
IgM anti-HPT78−108
[1]
<
[2]
0.326
[3]
40
[4]
42
[5]
1.0 (Ref)
[6]
0.005
[7]
0.841
[17] array · 7 items
[0]
≥
[1]
0.326
[2]
20
[3]
53
[4]
2.695 (1.356, 5.354)
[5]
[6]
[18] array · 8 items
[0]
IgM anti-HPT78−108 HNE
[1]
<
[2]
0.187
[3]
39
[4]
25
[5]
1.0 (Ref)
[6]
< 0.001
[7]
0.985
[19] array · 7 items
[0]
≥
[1]
0.187
[2]
21
[3]
70
[4]
5.235 (2.594, 10.565)
[5]
[6]
[20] array · 8 items
[0]
IgG anti-IGKC2−19
[1]
<
[2]
0.392
[3]
35
[4]
22
[5]
1.0 (Ref)
[6]
< 0.001
[7]
0.974
[21] array · 7 items
[0]
≥
[1]
0.392
[2]
25
[3]
73
[4]
4.679 (2.317, 9.449)
[5]
[6]
[22] array · 8 items
[0]
IgG anti-IGKC2−19 HNE
[1]
<
[2]
0.427
[3]
33
[4]
26
[5]
1.0 (Ref)
[6]
< 0.001
[7]
0.905
[23] array · 7 items
[0]
≥
[1]
0.427
[2]
27
[3]
69
[4]
3.206 (1.621, 6.340)
[5]
[6]
[24] array · 8 items
[0]
IgM anti-IGKC2−19
[1]
<
[2]
0.743
[3]
56
[4]
50
[5]
1.0 (Ref)
[6]
< 0.001
[7]
> 0.999
[25] array · 7 items
[0]
≥
[1]
0.743
[2]
4
[3]
45
[4]
12.655 (4.244, 37.734)
[5]
[6]
[26] array · 8 items
[0]
IgM anti-IGKC2−19 HNE
[1]
<
[2]
0.738
[3]
53
[4]
47
[5]
1.0 (Ref)
[6]
< 0.001
[7]
> 0.999
[27] array · 7 items
[0]
≥
[1]
0.738
[2]
7
[3]
48
[4]
8.095 (3.312, 19.780)
[5]
[6]
[28] array · 8 items
[0]
IgG anti-THRB328−345
[1]
<
[2]
0.154
[3]
19
[4]
7
[5]
1.0 (Ref)
[6]
< 0.001
[7]
0.951
[29] array · 7 items
[0]
≥
[1]
0.154
[2]
41
[3]
88
[4]
5.761 (2.228, 14.895)
[5]
[6]
[30] array · 8 items
[0]
IgG anti-THRB328−345 HNE
[1]
<
[2]
0.281
[3]
26
[4]
7
[5]
1.0 (Ref)
[6]
< 0.001
[7]
0.962
[31] array · 7 items
[0]
≥
[1]
0.281
[2]
34
[3]
88
[4]
9.524 (3.777, 24.012)
[5]
[6]
[32] array · 8 items
[0]
IgM anti-THRB328−345
[1]
<
[2]
0.791
[3]
46
[4]
56
[5]
1.0 (Ref)
[6]
0.029
[7]
0.697
[33] array · 7 items
[0]
≥
[1]
0.791
[2]
14
[3]
39
[4]
2.249 (1.086, 4.659)
[5]
[6]
[34] array · 8 items
[0]
IgM anti-THRB328−345 HNE
[1]
<
[2]
0.682
[3]
48
[4]
42
[5]
1.0 (Ref)
[6]
< 0.001
[7]
0.992
[35] array · 7 items
[0]
≥
[1]
0.682
[2]
12
[3]
53
[4]
5.043 (2.377, 10.696)
[5]
[6]
locator
section[15]/table-wrap[1]#Tab4
[6] object · 16 fields
id
asset:table:pmid:33568149:5
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:f4a3f91da1be96b7da6dfede15a9c320505696dae6dfaf7348e7a82847d76c89
bytes
1276
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[16]/table-wrap[1]#Tab5
version
null
note
Feature importance ranking of 4-hydroxy-2-nonenal (HNE)-protein adducts and autoantibody isotypes against unmodified and HNE-modified peptides in rheumatoid arthritis (RA) patients versus healthy controls (HCs) and osteoarthritis (OA) patients
structure object · 5 fields
pmcid
PMC7874460
section_index
16
section_title
Using serum anti-unmodified and anti-HNE-modified peptide autoantibodies to identify RA patients from HCs and OA patients
row_count
15
column_count
4
table object · 8 fields
label
Table 5
caption
Feature importance ranking of 4-hydroxy-2-nonenal (HNE)-protein adducts and autoantibody isotypes against unmodified and HNE-modified peptides in rheumatoid arthritis (RA) patients versus healthy controls (HCs) and osteoarthritis (OA) patients
rows array · 15 items
[0] array · 2 items
[0]
HC versus RA
[1]
OA versus RA
[1] array · 4 items
[0]
Score
[1]
Feature
[2]
Score
[3]
Feature
[2] array · 4 items
[0]
0.3496
[1]
IgM anti-HPT78−108 HNE
[2]
0.352
[3]
IgM anti-HPT78−108 HNE
[3] array · 4 items
[0]
0.2967
[1]
IgM anti-IGKC2−19
[2]
0.245
[3]
IgM anti-IGKC2−19
[4] array · 4 items
[0]
0.2921
[1]
IgM anti-IGKC2−19 HNE
[2]
0.223
[3]
IgM anti-IGKC2−19 HNE
[5] array · 4 items
[0]
0.1689
[1]
IgM anti-THRB HNE
[2]
0.186
[3]
IgG anti-HPT78−108 HNE
[6] array · 4 items
[0]
0.1395
[1]
IgG anti-THRB328−345
[2]
0.172
[3]
IgG anti-CFAH1121−1230
[7] array · 4 items
[0]
0.1382
[1]
IgG anti-THRB328−345 HNE
[2]
0.139
[3]
HNE adducts
[8] array · 4 items
[0]
0.1312
[1]
IgG anti-HPT78−108 HNE
[2]
0.134
[3]
IgM anti-THRB328−345 HNE
[9] array · 4 items
[0]
0.1186
[1]
IgG anti-IGKC2−19
[2]
0.128
[3]
IgG anti-CFAH1121−1230 HNE
[10] array · 4 items
[0]
0.1123
[1]
IgG anti-CFAH1121−1230
[2]
0.126
[3]
IgG anti-HPT78−108
[11] array · 4 items
[0]
0.1108
[1]
IgM anti-CFAH1121−1230
[2]
0.114
[3]
IgG anti-THRB328−345
[12] array · 4 items
[0]
0.1007
[1]
IgG anti-HPT78−108
[2]
[3]
[13] array · 4 items
[0]
0.0994
[1]
HNE adducts
[2]
[3]
[14] array · 4 items
[0]
0.0980
[1]
IgG anti-CFAH1121−1230 HNE
[2]
[3]
locator
section[16]/table-wrap[1]#Tab5
[7] object · 16 fields
id
asset:table:pmid:33568149:6
role
table
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Predictive performance using all 16 features in decision trees, random forests, and support vector machines for healthy controls (HCs) versus rheumatoid arthritis (RA) patients and osteoarthritis (OA) versus RA patients
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Using serum anti-unmodified and anti-HNE-modified peptide autoantibodies to identify RA patients from HCs and OA patients
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Predictive performance using all 16 features in decision trees, random forests, and support vector machines for healthy controls (HCs) versus rheumatoid arthritis (RA) patients and osteoarthritis (OA) versus RA patients
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Improved predictive performance using only selected features in decision trees, random forests, and support vector machines for healthy controls (HCs) versus rheumatoid arthritis (RA) patients and osteoarthritis (OA) versus RA patients
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Using serum anti-unmodified and anti-HNE-modified peptide autoantibodies to identify RA patients from HCs and OA patients
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Improved predictive performance using only selected features in decision trees, random forests, and support vector machines for healthy controls (HCs) versus rheumatoid arthritis (RA) patients and osteoarthritis (OA) versus RA patients
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As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs
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The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.
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As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33568149", "kind": "science-record", "revision": 7, "content_hash": "sha256:26a89902300d93a17f1e2b95c64a758884753aa9981fe51f7072c90831e8528f", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:03:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Isotypes of autoantibodies against novel differential 4-hydroxy-2-nonenal-modified peptide adducts in serum is associated with rheumatoid arthritis in Taiwanese women.", "doi": "10.1186/s12911-020-01380-y", "pmid": "33568149", "authors": ["Kai-Leun Tsai", "Che-Chang Chang", "Yu-Sheng Chang", "Yi-Ying Lu", "I-Jung Tsai", "Jin-Hua Chen", "Sheng-Hong Lin", "Chih-Chun Tai", "Yi-Fang Lin", "Hui-Wen Chang", "Ching-Yu Lin", "Emily Chia-Yu Su"], "journal": "BMC medical informatics and decision making", "year": 2021, "abstract": "BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients.\nMETHODS: Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Four novel differential HNE-modified peptide adducts, complement factor H (CFAH)1211-1230, haptoglobin (HPT)78-108, immunoglobulin (Ig) kappa chain C region (IGKC)2-19, and prothrombin (THRB)328-345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546) from RA patients vs. HCs. Further, we determined serum protein levels of CFAH, HPT, IGKC and THRB, HNE-protein adducts, and autoantibodies against unmodified and HNE-modified peptides. Significant correlations and odds ratios (ORs) were calculated.\nRESULTS: Levels of HPT in RA patients were greatly higher than the levels in HCs. Levels of HNE-protein adducts and autoantibodies in RA patients were significantly greater than those of HCs. IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgM anti-IGKC2-19 HNE may be considered as diagnostic biomarkers for RA. Importantly, elevated levels of IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 were positively correlated with the disease activity score in 28 joints for C-reactive protein (DAS28-CRP). Further, the ORs of RA development through IgM anti-HPT78-108 HNE (OR 5.235, p < 0.001), IgM anti-IGKC2-19 (OR 12.655, p < 0.001), and IgG anti-THRB328-345 (OR 5.761, p < 0.001) showed an increased risk. Lastly, we incorporated three machine learning models to differentiate RA from HC and OA, and performed feature selection to determine discriminative features. Experimental results showed that our proposed method achieved an area under the receiver operating characteristic curve of 0.92, which demonstrated that our selected autoantibodies combined with machine learning can efficiently detect RA.\nCONCLUSIONS: This study discovered that some IgG- and IgM-NAAs and anti-HNE M-NAAs may be correlated with inflammation and disease activity in RA. Moreover, our findings suggested that IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 may play heavy roles in RA development.", "claims": [{"id": "claim-method", "statement": "As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33568149", "locator": "sections[15] \"Associations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with RA patients compared to HCs\" paragraph 2", "quote": "As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33568149", "locator": "sections[25] \"Availability of data and materials\" paragraph 2", "quote": "The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33568149"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Data are however available from the authors upon reasonable request and with permission of the hospital.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Human Rheumatoid Arthritis LC-MSMS", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33568149:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9d4059dc3aa6f09919239c13474bec468b3d0fbabd72fe9b3543781606598c74", "bytes": 1271, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab1", "version": null, "note": "Differential 4-hydroxy-2-nonenal (HNE)-modified peptide adducts in rheumatoid arthritis (RA) patients compared to healthy controls (HCs)", "structure": {"pmcid": "PMC7874460", "section_index": 13, "section_title": "Measuring autoantibodies against unmodified and HNE-modified peptides", "row_count": 11, "column_count": 9}, "table": {"label": "Table 1", "caption": "Differential 4-hydroxy-2-nonenal (HNE)-modified peptide adducts in rheumatoid arthritis (RA) patients compared to healthy controls (HCs)", "rows": [["Proteina", "Modified peptideb", "Positionc", "Obs.d", "Calc.e", "dMf", "dMg", "Sequence foundwith modifications"], ["HC", "RA"], ["CFAH", "SHTLRTTCWDGKLEYPTCAK(+ 158)", "1211–1230", "858.439", "858.435", "0.0041", "5.4", "−", "+"], ["HRTGDEITYQCRNGFYPATRGNTAK(+ 138)", "284–308", "749.370", "749.372", "− 0.0018", "−1.8", "+", "−"], ["HPT", "AVGDKLPECEADDGC(+ 158)PKPPEIAHGYVEHSVR", "78–108", "869.925", "869.927", "− 0.0017", "−1.3", "−", "+"], ["ILGGHLDA(+ 156)K", "162–170", "540.329", "540.327", "0.0028", "6.1", "+", "−"], ["IGKC", "TVAA(+ 156)PSVFIFPPSDEQLK", "2–19", "701.384", "701.386", "− 0.0018", "−1.7", "−", "+"], ["TVA(+ 156)APSVFIFPPSDEQLK", "2–19", "1051.582", "1051.575", "0.0070", "7.1", "+", "+"], ["VYACEVTHQ(+ 158)GLSSPVTKSFNR", "83–103", "862.780", "862.785", "− 0.0044", "−4.5", "+", "−"], ["THRB", "TFGSGEADCGLRPLFEK(+ 156)K", "328–345", "1056.036", "1056.046", "− 0.0107", "−9.6", "−", "+"], ["TFGSGEADC(+ 140)GLRPL(+ 156)FEK", "328–344", "708.376", "708.375", "0.0009", "2.1", "+", "−"]], "row_count": 11, "column_count": 9, "numeric_cells": 54, "header_rows": 2, "locator": "section[13]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:33568149:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f49ea03d5d8f9e0e1ad1b5040350090796c410eff7eadeed5b22abf8c80b9fdc", "bytes": 4141, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#Tab2", "version": null, "note": "Comparisons of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides in rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients compared to healthy controls (HCs)", "structure": {"pmcid": "PMC7874460", "section_index": 13, "section_title": "Measuring autoantibodies against unmodified and HNE-modified peptides", "row_count": 34, "column_count": 8}, "table": {"label": "Table 2", "caption": "Comparisons of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides in rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients compared to healthy controls (HCs)", "rows": [["Peptides", "RA vs. HC", "OA versus HC", "p value a"], ["AUC (95%CI)", "Sensitivity (95%CI)", "Specificity (95%CI)", "AUC (95%CI)", 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(58.6–82.6)", "55.0% (41.6–67.9)", "0.53 (0.41–0.65)", "51.4% (34.0–68.6)", "46.7% (33.7–60.0)", "0.3711"], ["Cutoff (OD450)", "", "> 0.64", "", "", "< 0.64", "", ""], ["IgG anti-HPT78−108 HNE", "0.66 (0.57–0.76)", "71.7% (58.6–82.6)", "48.3% (35.2–61.6)", "0.58 (0.46–0.70)", "62.9% (44.9–78.5)", "55.0% (41.6–67.9)", "0.8974"], ["Cutoff (OD450)", "", "> 0.25", "", "", "< 0.25", "", ""], ["IgM anti-HPT78−108", "0.67 (0.57–0.77)", "71.7% (58.6–82.6)", "56.7% (43.2–69.4)", "0.53(0.40–0.66)", "51.4%(33.9–68.6)", "50.0%(36.8– 63.2)", "0.2823"], ["Cutoff (OD450)", "", "> 0.30", "", "", "< 0.29", "", ""], ["IgM anti-HPT78−108 HNE", "0.89 (0.80–0.93)", "86.7% (75.4–94.1)", "66.7% (53.3–78.3)", "0.58 (0.46–0.69)", "65.7% (47.8–80.9)", "55.0% (41.6–67.9)", "< 0.0001"], ["Cutoff (OD450)", "", "> 0.20", "", "", "> 0.16", "", ""], ["IgG anti-IGKC2−19", "0.72 (0.62–0.81)", "80.0% (67.7–89.2)", "60.0% (46.5–72.4)", "0.59 (0.47–0.70)", "65.7% (47.8–80.9)", "53.3% (40.0–66.3)", "0.1471"], ["Cutoff 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(67.7–89.2)", "53.3% (40.0–66.3)", "0.60 (0.48–0.71)", "68.6% (50.7–83.2)", "50.0% (36.8–63.2)", "0.0087"], ["Cutoff (OD450)", "", "> 0.32", "", "", "> 0.31", "", ""], ["IgM anti-THRB328−345", "0.63 (0.53–0.73)", "63.3% (50.0–75.4)", "53.3% (40.0–66.3)", "0.56 (0.44–0.68)", "60.0% (42.1–76.1)", "53.3% (40.0–66.3)", "0.5845"], ["Cutoff (OD450)", "", "> 0.61", "", "", "> 0.60", "", ""], ["IgM anti-THRB328−345 HNE", "0.78 (0.69–0.86)", "76.7% (64.0–86.6)", "71.7% (58.6–82.6)", "0.56 (0.44–0.68)", "65.7% (47.8–80.9)", "46.7% (33.7–60.0)", "0.0001"], ["Cutoff (OD450)", "", "> 0.64", "", "", "> 0.52", "", ""]], "row_count": 34, "column_count": 8, "numeric_cells": 182, "header_rows": 2, "locator": "section[13]/table-wrap[2]#Tab2"}}, {"id": "asset:table:pmid:33568149:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fc8ce78dc9008b66d2779170f9ee12b3a82131de07dfc5cf2ebe99ea2c736523", "bytes": 2775, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#Tab3", "version": null, "note": "Correlations between autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides and clinical variables in rheumatoid arthritis (RA) patients (n = 60)", "structure": {"pmcid": "PMC7874460", "section_index": 14, "section_title": "Correlations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with clinical variables in RA patients", "row_count": 18, "column_count": 13}, "table": {"label": "Table 3", "caption": "Correlations between autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides and clinical variables in rheumatoid arthritis (RA) patients (n = 60)", "rows": [["", "DAS28", "RF", "Anti-CCP", "CRP", "ESR", "HNE adduct"], ["r", "p value", "r", "p value", "r", "p value", "r", "p value", "r", "p value", "r", "p value"], ["IgG anti-CFAH1121−1230", "0.1580", "0.2279", "0.0968", "0.4696", "0.0108", "0.9347", "0.0229", "0.8659", "0.2076", "0.1115", "− 0.009", "0.9458"], ["IgG anti-CFAH1121−1230 HNE", "− 0.0441", "0.7379", "− 0.0035", "0.9794", "− 0.0359", "0.7852", "− 0.1446", "0.2831", "0.1359", "0.3006", "− 0.0082", "0.9501"], ["IgM anti-CFAH1121−1230", "0.0424", "0.7477", "0.0626", "0.6406", "0.2100", "0.1073", "− 0.0164", "0.9036", "0.0756", "0.5658", "− 0.0503", "0.7026"], ["IgM anti-CFAH1121−1230HNE", "0.0377", "0.7748", "0.0435", "0.746", "0.2192", "0.0924", "− 0.0821", "0.5435", "0.1343", "0.3063", "0.0302", "0.8186"], ["IgG anti-HPT78−108", "0.0929", "0.4804", "0.1386", "0.2996", "0.0659", "0.6169", "0.1138", "0.3994", "0.1695", "0.1954", "0.0754", "0.5670"], ["IgG anti-HPT78−108 HNE", "− 0.0266", "0.8400", "0.0195", "0.8848", "0.2782", "0.0314", "0.1081", "0.4236", "0.1346", "0.3052", "− 0.0593", "0.6529"], ["IgM anti-HPT78−108", "− 0.0171", "0.8969", "0.1711", "0.1992", "0.0877", "0.5051", "− 0.0591", "0.6623", "0.0074", "0.9555", "− 0.0453", "0.7310"], ["IgM anti-HPT78−108 HNE", "0.2703", "0.0367", "0.6140", "< 0.0001", "0.0294", "0.8238", "0.1236", "0.3596", "0.2180", "0.0943", "0.1836", "0.1603"], ["IgG anti-IGKC2−19", "− 0.3538", "0.0056", "− 0.1144", "0.3926", "− 0.0023", "0.9862", "− 0.1061", "0.4320", "− 0.123", "0.3597", "0.2097", "0.1078"], ["IgG anti-IGKC2−19 HNE", "0.6023", "− 0.3432", "0.0073", "− 0.1997", "0.1328", "0.1253", "0.3399", "− 0.0524", "0.6986", "− 0.0328", "0.8035", "0.0686"], ["IgM anti-IGKC2−19", "0.2816", "0.0293", "0.5674", "< 0.0001", "− 0.0588", "0.6553", "0.0511", "0.7059", "0.2692", "0.0376", "0.2667", "0.0394"], ["IgM anti-IGKC2−19 HNE", "0.2487", "0.0553", "0.5404", "< 0.0001", "0.2439", "0.0604", "0.0429", "0.7512", "0.2985", "0.0205", "0.2709", "0.0363"], ["IgG anti-THRB328−345", "0.2703", "0.0367", "0.6140", "< 0.0001", "0.2439", "0.0604", "0.1236", "0.3596", "0.218", "0.0943", "0.1836", "0.1603"], ["IgG anti-THRB328−345 HINE", "0.1274", "0.3320", "0.3072", "0.019", "0.2549", "0.0494", "− 0.0575", "0.6712", "0.1341", "0.307", "0.0170", "0.8972"], ["IgM anti-THRB328−345", "− 0.0637", "0.6290", "0.2207", "0.096", "− 0.0365", "0.7821", "− 0.0292", "0.8293", "− 0.1513", "0.2473", "− 0.2796", "0.0305"], ["IgM anti-THRB328−345 HNE", "0.0818", "0.5345", "0.2845", "0.0304", "− 0.0438", "0.7397", "0.081", "0.549", "0.2597", "0.0451", "0.1036", "0.4310"]], "row_count": 18, "column_count": 13, "numeric_cells": 209, "header_rows": 2, "locator": "section[14]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:33568149:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7745041f544f84fa98b9d183d75a9b5c48f42ba2866ea9a36a83b34c13b7b7bd", "bytes": 2756, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#Tab4", "version": null, "note": "Associations of 4-hydroxy-2-nonenal (HNE)-protein adducts and autoantibody isotypes against unmodified and HNE-modified peptides in rheumatoid arthritis (RA) patients vs. healthy controls (HCs)", "structure": {"pmcid": "PMC7874460", "section_index": 15, "section_title": "Associations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with RA patients compared to HCs", "row_count": 36, "column_count": 8}, "table": {"label": "Table 4", "caption": "Associations of 4-hydroxy-2-nonenal (HNE)-protein adducts and autoantibody isotypes against unmodified and HNE-modified peptides in rheumatoid arthritis (RA) patients vs. healthy controls (HCs)", "rows": [["Risk factor", "", "Cutoff", "HC", "RA", "Age-adjusted logistic regression modela", "p value", "Power"], ["(n)", "(n)", "OR (95% CI)"], ["HNE-protein adduct", "<", "2.386", "26", "24", "1.0 (Ref)", "0.014", "0.743"], ["≥", "2.386", "34", "71", "2.413 (1.193, 4.880)", "", ""], ["IgG anti-CFAH1121−1230", "<", "0.175", "14", "8", "1.0 (Ref)", "0.013", "0.874"], ["≥", "0.175", "46", "87", "3.293 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