Significance of co-positivity for anti-dsDNA, -nucleosome, and -histone antibodies in patients with lupus nephritis

Figures & data

Table 1. Baseline characteristics and laboratory findings of lupus nephritis (LN) patients according to their 3-pos status.

	All patients (n = 102)	3-pos (n = 44)	Non 3-pos (n = 58)	p value
Age at LN onset, years	35.4 ± 10.9	32.9 ± 9.87	37.2 ± 11.3	.058
Female, n (%)	89 (87.3 %)	39 (88.6)	50 (86.2)	.479
Disease duration at LN onset, months	32.8 ± 51.7	36.1 ± 50.9	30.2 + 52.7	.385
Hypertension at LN onset, n (%)	39 (38.2 %)	14 (31.8)	25 (43.9)	.218
Diabetes mellitus at LN onset, n (%)	4 (3.9%)	1 (2.3)	3 (5.3)	.412
Laboratory findings
White blood cells, /mm^3	6340.7 ± 3856.9	5511.4 ± 3029.7	6969.9 ± 4265.7	.085
Lymphocytes, /mm^3	1279.8 ± 1088.1	955.4 ± 459.6	1525.9 ± 1339.9	.004
Hemoglobin, g/dL	10.4 ± 2.07	10.1 ± 1.94	10.6 ± 2.15	.232
Platelets, 10^3/ul	209.4 ± 103.6	205.4 ± 99.9	211.8 ± 108.5	.834
ESR, mm/hr	47.1 ± 34.8	42.1 ± 32.6	46.7 ± 36.6	.751
CRP, mg/dL	0.68 ± 0.92	0.60 ± 0.60	0.74 ± 1.10	.764
Albumin, mg/dL	3.15 ± 0.92	3.17 ± 0.92	3.12 ± 0.92	.695
Serum Cr, mg/mL	0.95 ± 0.64	0.84 ± 0.42	0.98 ± 0.62	.217
eGFR, ml/min/1.72m^2	115.1 ± 67.7	115.9 ± 50.9	111.2 ± 74.9	.191
Proteinuria, g/24 h	3.55 ± 2.87	3.78 ± 3.04	3.38 ± 2.81	.466
Proteinuria > 3.5 g/24 h	35 (34.3%)	20 (45.5%)	15 (25.9)	.039
Urine sediments	63 (61.8%)	34 (77.3)	29 (50.0)	.005
SLEDAI-2K score	12.5 ± 4.8	14.2 ± 4.67	11.3 ± 4.87	.002
Renal SLEDAI-2K score	6.27 ± 2.07	7.00 ± 1.75	5.72 ± 2.13	.002
Non-renal SLEDAI-2K score	6.25 ± 4.33	7.18 ± 4.62	5.53 ± 4.00	.117

Unless otherwise indicated, the values are mean ± standard deviation. The presence of urinary sediments was defined as >5 RBCs and >5 WBCs per high power field and/or cellular casts. LN: lupus nephritis; 3-pos: simultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; Cr: creatinine; eGFR: estimated glomerular filtration rate; SLEDAI-2K: Systemic Lupus Erythematosus Disease Activity Index-2000.

Table 2. Autoantibodies and complement levels in LN patients according to 3-pos status.

	All patients (n = 102)	3-pos (n = 44)	Non 3-pos (n = 58)	p value
Autoantibodies
Antinuclear, n (%)	99 (97.1%)	41 (95.3)	56 (98.2)	.401
Anti-dsDNA > 7, n (%)	86 (84.3%)	44 (100)	42 (74.2)	<.001
Anti-dsDNA	466.9 ± 1044.8	908.3 ± 1430.5	143.9 ± 332.4	.001
Anti-Sm, n (%)	45 (44.1%)	22 (50.0)	23 (39.7)	.297
Anti-RNP, n (%)	49 (48.0%)	27 (61.4)	22 (37.9)	.019
Anti-Ro/SS-A, n (%)	70 (68.6%)	26 (59.1)	44 (75.9)	.071
Anti-La/SS-B, n (%)	29 (28.4%)	11 (25)	18 (31)	.503
Anti-nucleosome, n (%)	69 (67.6%)	44 (100)	25(43.1)	<.001
Anti-histone, n (%)	54 (52.9%)	44 (100)	10 (17.2)	<.001
Anti-ribosomal P, n (%)	35 (34.3)	19 (43.2)	16 (27.6)	.100
Lupus anticoagulant, n (%)	16 (14.7%)	4 (9.5)	6 (11.1)	.538
Anti-phospholipid, n (%)	25 (26.9)	10 (25.0)	15 (28.3)	.722
Complement levels
C3	57.1 ± 28.3	48.6 ± 23.9	63.2 ± 29.8	.023
C4	10.4 ± 8.27	9.73 ± 8.72	11.0 ± 7.95	.189

Unless otherwise indicated, the values are mean ± standard deviation. LN: lupus nephritis; 3-pos: simultaneous positivity for anti-dsDNA, -nucleosome, and -histone antibodies.

Table 3. Associations of autoantibodies with renal biopsy findings in patients with lupus nephritis.

	Anti-dsDNA			Anti-nucleosome			Anti-histone			Co-positivity (n)
	Positive (n = 86)	Negative (n = 16)	p value	Positive (n = 69)	Negative (n = 33)	p value	Positive (n = 54)	Negative (n = 48)	p value	0 n = 8	1 n = 23	2 n = 27	3 n = 44	p for trend	p for trend*
Activity score	5.99 ± 4.39	3.69 ± 3.40	.078	6.25 ± 4.26	4.33 ± 4.21	.042	6.85 ± 4.20	4.25 ± 4.01	.002	1.88 ± 2.53	4.17 ± 3.81	6.26 ± 4.41	6.68 ± 4.29	.011	.033
Chronicity score	1.76 ± 1.39	2.50 ± 1.89	.125	1.84 ± 1.37	1.94 ± 1.75	.937	1.94 ± 1.37	1.79 ± 1.63	.447	2.75 ± 2.05	1.43 ± 1.53	2.15 ± 1.56	1.77 ± 1.25	.175	.525
Activity score (>12), n (%)	5 (31.3)	46 (53.5)	.086	38 (55.1)	13 (39.4)	.138	34 (66.7)	17 (35.4)	.005	1 (12.5)	8 (34.8)	16 (59.3)	26 (59.1)	.029
Chronicity score (>4), n (%)	3 (18.8)	10 (11.6)	.331	8(11.6)	5 (15.2)	.614	6 (11.1)	7 (14.6)	.600	1 (12.5)	3 (13.0)	6 (22.2)	3 (6.8)	.311
ISN/RPS classification, n (%)														.015	.045
I	8 (9.3)	3 (18.8)	.372	6 (8.7)	5 (15.2)	.328	2 (3.7)	9 (18.8)	.023	2 (25.0)	4(17.9)	3 (11.1)	2 (4.5)
II	7 (8.1)	3 (18.8)	.189	4 (5.8)	6 (18.2)	.073	4 (7.4)	6 (12.5)	.510	3 (37.5)	3 (13.0)	0 (0.0)	4 (9.1)
III	21 (24.4)	3 (18.8)	.757	19 (27.5)	5 (15.2)	.216	17 (31.5)	7 (14.6)	.061	0 (0.0)	3 (13.0)	9 (33.1)	12 (27.3)
IV	43 (50.0)	7 (25.0)	.100	35 (50.7)	12 (36.4)	.206	29 (53.7)	18 (37.5)	.115	1 (12.5)	9(39.1)	13(48.1)	24(54.5)
V	7 (8.1)	3 (18.8)	.189	5 (7.2)	5 (15.2)	.286	2 (3.7)	8 (16.7)	.043	2 (25.0)	4(17.9)	2 (7.4)	2(4.5)

Unless otherwise indicated, the values are mean ± standard deviation.

* Bonferroni corrected p-value.

Table 4. Treatment and clinical outcomes of LN patients according to 3-pos status.

	All patients (n = 102)	3-pos (n = 44)	Non 3-pos (n = 58)	p value
Treatment before LN diagnosis
Hydroxychloroquine	59 (57.8)	29 (65.9)	30 (50.8)	.151
Any immunosuppressive agent	20 (19.6)	12 (27.3)	8 (13.8)	.089
Treatment after LN diagnosis
Hydroxychloroquine (>80% use during follow up)	77 (75.2)	35 (79.5)	42 (72.4)	.407
Induction therapy				.222
CYC	35 (34.3)	18 (40.9)	17 (29.3)
Non-CYC	67 (65.7)	26 (59.1)	41 (70.7)
Statin	35 (34.3)	13 (29.5)	22 (37.9)	.377
ACEi or ARB	83 (81.4)	37 (84.1)	46 (79.3)	.539
Clinical outcomes
1-year CR	50 (49.0)	19 (43.2)	31 (53.4)	.304
Relapse	52 (51.0)	24 (54.5)	28 (48.3)	.530
Rapid eGFR progression*	51 (50.0)	28 (63.6)	23 (39.7)	.016
ESRD	11 (10.8)	6 (13.6)	5 (8.6)	.419
Death	3 (3.0)	1 (2.3)	2 (3.6)	.720

All values are reported as percentages. LN: lupus nephritis; 3-pos: simultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies; CYC: cyclophosphamide; ACEi: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; CR: complete renal response; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease.

* Rapid eGFR progression is defined as an absolute annual decline of eGFR ≥5 ml/min/1.73 m² each year and an eGFR at the last follow-up of <90 ml/min/1.73 m².

Data availability statement

The full original protocol and dataset can be accessed upon request for academic researchers by contacting Professor Shin-Seok Lee ([email protected]).