Antiphospholipid Antibody Positivity and the Clinical Outcomes of Patients with Systemic Lupus Erythematosus

Seoung Wan Nam; Soo-Kyung Cho; Dam Kim; Kyung-Eun Lee; Dong-Jin Park; Shin-Seok Lee; Yoon-Kyoung Sung

doi:10.4078/jrd.2018.25.4.239

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Nam, Cho, Kim, Lee, Park, Lee, and Sung: Antiphospholipid Antibody Positivity and the Clinical Outcomes of Patients with Systemic Lupus Erythematosus

Original Article

J Rheum Dis 2018;25(4):239-247.

Published online: 31 October 2018

DOI: https://doi.org/10.4078/jrd.2018.25.4.239

Antiphospholipid Antibody Positivity and the Clinical Outcomes of Patients with Systemic Lupus Erythematosus

Seoung Wan Nam¹, Soo-Kyung Cho¹, Dam Kim¹, Kyung-Eun Lee², Dong-Jin Park², Shin-Seok Lee², Yoon-Kyoung Sung¹

¹Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

²Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea

Corresponding to: Yoon-Kyoung Sung, http://orcid.org/0000-0001-6691-8939 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. E-mail: sungyk@hanyang.ac.kr

Received 2 April 201824 May 2018 Accepted 9 June 2018

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To identify the prevalence of antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) patients and determine the relationship between aPL and the clinical outcomes.

Methods

SLE patients with aPL test results within 2 years of enrollment were selected from Korean lupus network study. They were classified into two groups: aPL (+) group, patients positive for at least one aPL, and aPL (−) group, patients without an aPL. The clinical characteristics of the two groups were compared and the role of aPL in the risk of chronic kidney disease (CKD) in SLE patients was examined.

Results

Among the 469 SLE patients, 69 (14.7%) had at least one aPL. The prevalence of cerebrovascular disease and CKD was higher in the aPL (+) group than in the aPL (−) group (10.1% vs. 1.8% and 13.8% vs. 5.1%, p＜0.05). Multivariable regression analysis showed that the aPL positivity (odds ratio=3.93, 95% confidence interval=1.48∼10.47) was associated with the risk of CKD after adjusting for age, disease duration, and lupus nephritis history.

Conclusion

The prevalence of aPL in Korean SLE patients is 14.7%, and it is associated with a higher prevalence of cerebrovascular disease and CKD in SLE patients. The aPL positivity is independently associated with the risk of CKD in SLE patients.

Keywords: Antiphospholipid antibody, Systemic lupus erythematosus, Chronic kidney disease

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Figure 1.

Patient selection flow. SLE: systemic lupus erythematosus, aPL: antiphospholipid antibody.

Table 1.

Distribution of antiphospholipid antibody positivity patterns in antiphospholipid antibody positive patients

Positive antiphospholipid antibodies	Number (%)
aCL (+)*	7 (10.1)
aβ₂ GPI (+)^†	2 (2.9)
LAC (+)^‡	50 (72.5)
aCL (+) & aβ₂ GPI (+)	5 (7.2)
aCL (+) & LAC (+)	3 (4.3)
aβ₂ GPI (+) & LAC (+)	1 (1.4)
aCL (+) & aβ₂ GPI (+) & LAC (+)	1 (1.4)
Total	69 (100)

aCL: anticardiolipin antibody, aβ₂ GPI: anti-β₂-glycoprotein I antibody, LAC: lupus anticoagulant, immunoglobulin. Ig:

^* IgG or IgM aCL ＞ 40 GPLU/ml.

^† IgG or IgM aβ₂ GPI ＞ 40 SGU/ml.

^‡ LAC, detected according to the guidelines of the International Society on Thrombosis and Haemostasis.

Table 2.

Demographic and clinical characteristics of patients with or without antiphospholipid antibody

Variable	Total (n=469)	aPL (+) (n=69)	aPL (−) (n=400)	p-value
Age (yr)	40.4±11.3	40.6±11.0	40.4±11.4	0.85
Sex, female	436 (93.0)	64 (92.8)	372 (93.0)	1.00
Disease duration (yr)	8.3±6.3	7.3±6.4	8.5±6.3	0.14
Smoking, ever	53 (11.3)	15 (21.7)	38 (9.5)	＜0.01
ACR criteria at diagnosis
Malar rash	224 (47.8)	28 (40.6)	196 (49)	0.25
Discoid rash	24 (5.1)	5 (7.2)	19 (4.8)	0.57
Photosensitivity	140 (29.9)	22 (31.9)	118 (29.5)	0.80
Oral ulcer	126 (26.9)	13 (18.8)	113 (28.3)	0.14
Arthritis	242 (51.6)	33 (47.8)	209 (52.3)	0.58
Serositis	86 (18.3)	10 (14.5)	76 (19.0)	0.47
Renal disorder	173 (36.9)	21 (30.4)	152 (38.0)	0.29
Neurologic disorder	20 (4.3)	4 (5.8)	16 (4.0)	0.72
Hematologic disorder	305 (65.0)	51 (73.9)	254 (63.5)	0.12
Hemolytic anemia	40 (8.5)	7 (10.1)	33 (8.3)	0.77
Leukopenia	209 (44.6)	31 (44.9)	178 (44.5)	1.00
Lymphopenia	79 (16.8)	16 (23.2)	63 (15.8)	0.18
Thrombocytopenia	101 (21.5)	20 (29.0)	81 (20.3)	0.14
Immunologic disorder	425 (90.6)	69 (100.0)	356 (89.0)	＜0.01
Anti-dsDNA Ab	381 (81.2)	58 (84.1)	323 (80.8)	0.63
Anti-Sm Ab	136 (29.0)	18 (26.1)	118 (29.5)	0.67
Antiphospholipid antibody*	137 (29.2)	69 (100.0)	68 (17.0)	＜0.01
Positive ANA	459 (97.9)	68 (98.6)	391 (97.8)	1.00
Number of ACR criteria	4.7±1.4	4.7±1.3	4.8±1.4	0.76
SELENA SLEDAI score	3.7±3.6	4.0±3.6	3.7±3.6	0.45
SELENA SLEDAI flare index
Flare, regardless of severity	19 (4.1)	3 (4.3)	16 (4.0)	0.75
SLICC/ACR damage index	0.3±0.7	0.5±0.9	0.3±0.7	0.04
Medication	385 (82.1)	57 (82.6)	328 (82.0)	1.00
Corticosteroid
Mean dose (mg/d)	7.9±8.5	7.1±5.8	8.1±8.9	0.42
Hydroxychloroquine	430 (91.7)	59 (85.5)	371 (92.8)	0.08
Methotrexate	18 (3.8)	5 (7.2)	13 (3.3)	0.21
Tacrolimus	41 (8.7)	6 (8.7)	35 (8.8)	1.00
Azathioprine	77 (16.4)	10 (14.5)	67 (16.8)	0.77
Mycophenolate mofetil	72 (15.4)	8 (11.6)	64 (16.0)	0.45
Cyclosporine	13 (2.8)	3 (4.3)	10 (2.5)	0.64
IV cyclophosphamide	6 (1.3)	2 (2.9)	4 (1.0)	0.47
Aspirin	86 (18.3)	35 (50.7)	51 (12.8)	＜0.01
Warfarin	13 (2.8)	3 (4.3)	10 (2.5)	0.64

Values are presented as mean±standard deviation or number (%). aPL: antiphospholipid antibody, ACR: American College of Rheumatology, Anti-dsDNA Ab: anti-double stranded DNA antibody, Anti-Sm Ab: anti-Smith antibody, ANA: antinuclear antibody, SELENA SLEDAI: Safety of Estrogens in Lupus Erythematosus National Assessment– Systemic Lupus Erythematosus Disease Activity Index, SLICC: Systemic Lupus International Collaborating Clinics, IV: intravenous, Ig: immunoglobulin, LAC: lupus anticoagulant.

^* Positive finding of antiphospholipid antibodies based on 1) IgG aCL ≥10 GPLU/ml or IgM aCL ≥7 MPLU/ml, 2) LAC, detected according to the guidelines of the International Society on Thrombosis and Haemostasis, or 3) a false positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization of fluorescent treponemal antibody absorption test.

Table 3.

Prevalence of vascular comorbidities, renal manifestations, and obstetric complications associated with antiphospholipid antibody

Variable	aPL (+) (n=69)	aPL (−) (n=400)	p-value	p-value*
Vascular comorbidities (at enrollment)
Ischemic heart disease	0 (0)	5 (1.3)	0.77	0.09
Peripheral vascular disorder	0 (0)	3 (0.8)	1.00	0.54
Cerebrovascular disease	7 (10.1)	7 (1.8)	＜0.01	0.02
Renal manifestations
Chronic kidney disease, stage ≥3^† (n=440)	9/65 (13.8)	19/375 (5.1)	0.01	＜0.01
Serum creatinine level (mg/dl)	0.87±0.63	0.72±0.24	＜0.01
eGFR (ml/min/1.73 m²)	90.85±29.07	101.73±32.86	0.01	0.05
Lupus nephritis	20 (29.0)	115 (28.8)	0.97	0.87
Severe lupus nephritis (class ≥ III)^‡	8 (11.6)	77 (19.3)	0.13	0.19
Obstetric complication^§ (n=436)	n=64	n=372
History of spontaneous abortion	6 (9.4)	34 (9.1)	1.00	0.75
Number of spontaneous abortion			0.54	0.47
1	6 (9.4)	22 (5.9)
2	0 (0)	8 (2.2)
3	0 (0)	2 (0.5)
4	0 (0)	2 (0.5)
History of stillbirth	2 (3.1)	7 (1.6)	0.87	0.81

Values are presented as number (%) or mean±standard deviation. aPL: antiphospholipid antibody, eGFR: estimated glomerular filtration rate.

^* p-value after adjustment for smoking and aspirin;

^† Defined as estimated glomerular filtration rate ＜60 ml/min/1.73 m².

^‡ Defined as lupus nephritis International society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, and V;

^§ Obstetric complications were only evaluated in female patients (n=436).

Table 4.

Univariable and multivariable logistic regression analyses of the variables associated with increased risk of chronic kidney disease (stage ≥3)

Variable	Univariable analysis		Multivariable analysis
Variable	Odds ratio (95% CI)	p-value	Odds ratio (95% CI)	p-value
Age (yr)	1.05 (1.01∼1.09)	＜0.01	1.07 (1.03∼1.12)	＜0.01
Sex, male	0.51 (0.07∼3.88)	0.51
Disease duration (yr)	1.08 (1.02∼1.14)	＜0.01	1.07 (1.01∼1.14)	0.03
Smoking history	0.60 (0.14∼2.60)	0.49
Lupus nephritis history	5.59 (2.46∼12.71)	＜0.01	5.36 (2.02∼14.21)	＜0.01
Antiphospholipid antibody	3.01 (1.30∼6.99)	0.01	3.93 (1.48∼10.47)	＜0.01
Anti-cardiolipin antibody*	2.19 (0.47∼10.14)	0.32
Anti-β₂-glycoprotein I antibody^†	2.51 (0.29∼21.57)	0.40
Lupus anticoagulant^‡	3.26 (1.36∼7.84)	＜0.01
Anti-dsDNA Ab	2.04 (0.60∼6.92)	0.25
Anti-Sm Ab	0.51 (0.19∼1.36)	0.18
Medication
Corticosteroid	6.01 (0.80∼44.92)	0.08	7.48 (0.92∼60.50)	0.06
Hydroxychloroquine	0.39 (0.14∼1.09)	0.07	0.65 (0.19∼2.21)	0.49
Methotrexate	2.19 (0.47∼10.14)	0.32
Tacrolimus	2.50 (0.89∼7.00)	0.08	1.17 (0.35∼3.89)	0.80
Azathioprine	1.48 (0.58∼3.80)	0.41
Mycophenolate mofetil	3.32 (1.46∼7.55)	＜0.01	2.13 (0.77∼5.89)	0.14
Cyclosporine	1.35 (0.17∼10.85)	0.78
IV cyclophosphamide	3.02 (0.34∼26.73)	0.32
NSAIDs	1.51 (0.55∼4.13)	0.43
Aspirin	1.57 (0.65∼3.84)	0.32

CI: confidence interval, Anti-dsDNA Ab: anti-double stranded DNA antibody, Anti-Sm Ab: anti-Smith antibody, IV: intravenous, NSAIDs: nonsteroidal anti-inflammatory drugs, Ig: immunoglobulin, aCL: anticardiolipin antibody, aβ₂ GPI: anti-β₂-glycoprotein I antibody.

^* IgG or IgM aCL ＞40 GPLU/ml.

^† IgG or IgM aβ₂GPI ＞40 SGU/ml.

^‡ LAC, detected according to the guidelines of the International Society on Thrombosis and Haemostasis, LAC: lupus anticoagulant.

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