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Abstract Number: 788

Unresolving C4 Hypocomplementemia Associates with a Different Spectrum of Disease in SLE and Is More Important Than Transiently Low Levels

Laura Durcan1, Wei Fu2 and Michelle Petri3, 1University of Washington, Seattle, WA, 2Division of Rheumatology, School of Medicine, Johns Hopkins University, Baltimore, MD, 3Rheumatology Division, Johns Hopkins University School of Medicine, Baltimore, MD

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: SLE and complement

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Session Information

Date: Sunday, November 13, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment - Poster I: Clinical Trial Design and Current Therapies

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Hypocomplementemia is common in systemic lupus erythematosus (SLE) and is included in classification criteria and disease activity indices. Whether persistently low complement levels (C3, C4 and both) are more important as serological markers, than levels which transiently drop in SLE is unknown. This work was undertaken to characterize SLE patients with persistent hypocomplementemia and to compare them to those with intermittently low levels.

Methods: Patients were identified as part of a longitudinal lupus cohort. Levels of C3 and C4 were measured quarterly, by nephelometry. Patients were considered with complement levels (either C3, C4 or both), which never returned to the normal range on longitudinal follow-up. Further analysis included those with intermittently low levels. To assess associated clinical manifestations, univariate and multivariate logistic regression were used. The multivariate analysis controlled for ethnicity, and gender.

Results: 2399 SLE patients, 53% Caucasian and 38% African-American, were evaluated. A history of ever having had low C3 was present in 55% and low C4 in 47%. There were 83 (4.0%) patients with persistently low C3, which never normalized and 65 (3.2%) individuals with persistently low C4. The clinical manifestations associated with persistent hypocomplementemia are outlined in Table 1 whilst those associated with transiently low levels are in Table 2. Persistently low C3 associates with renal, hematologic and serologic abnormalities with similar manifestations in those with intermittently low C3. Contrarily, chronically low C4 associates with a myriad of abnormalities, serologic and hematologic whilst intermittently low levels associate only with a positive anti-double stranded DNA, anticardiolipin and a false positive rapid plasma reagin. Persistently low C3 and C4 in combination associated with serologic abnormalities and the presence of antiphospholipid antibodies, whilst in those with transiently low levels there was cutaneous, neurologic, hematologic and immunologic dysfunction demonstrated.

Conclusion: Low complement is an important finding in SLE. Transiently low C4 is a weak marker which associates with few clinical manifestations. However, chronically low C4, which may represent a subset of patients with genetic deficiency, associates with a different spectrum of disease and has different, more severe, clinical implications.

SLE manifestation  

Persistently low C3

P value

Persistently low C4

P value

Persistently low C3 and C4

P value
Malar rash  

1.02 (0.6,1.75)

0.9380

0.83 (0.44,1.56)

0.5591

1.54 (0.67,3.54)

0.3083
Discoid rash  

1.35 (0.71,2.55)

0.3607

1.34 (0.57,3.12)

0.5009

1.03 (0.34,3.1)

0.9629
Photosensitivity  

0.74 (0.43,1.27)

0.2770

1.04 (0.54,2)

0.8948

0.82 (0.36,1.88)

0.6435
Oral/Nasal Ulcers  

0.92 (0.54,1.58)

0.7647

0.85 (0.45,1.61)

0.6217

0.53 (0.23,1.25)

0.1495
Arthritis  

1.54 (0.81,2.91)

0.1885

0.93 (0.47,1.84)

0.8427

1.75 (0.64,4.78)

0.2738
Serositis Pleurisy

1.17 (0.69,2.01)

0.5583

1.29 (0.68,2.43)

0.4301

1 (0.43,2.33)

0.9946
Pericarditis

1.67 (0.91,3.06)

0.0994

1.88 (0.89,3.94)

0.0959

0.47 (0.11,2.05)

0.3163
Renal disorder  

3.15 (1.39,7.15)

0.0061

0.67 (0.09,5.06)

0.7007

2.04 (0.46,9.07)

0.3492
Neurologic Seizures

1.14 (0.47,2.75)

0.7675

0.81 (0.24,2.69)

0.7307

0.45 (0.06,3.38)

0.4376
Psychosis

1.19 (0.27,5.16)

0.8200

1.09 (0.14,8.31)

0.9345

1.69 (0.22,13.11)

0.6181
Hematologic Hemolytic anemia

1.51 (0.62,3.7)

0.3627

5.01 (2.32,10.82)

<.0001

0.59 (0.08,4.49)

0.6125
Leukopenia

3.57 (2.02,6.32)

<.0001

2.7 (1.43,5.11)

0.0022

2.61 (1.14,5.98)

0.0238
Lymphopenia

1.96 (1.15,3.35)

0.0140

2.88 (1.5,5.53)

0.0014

1.12 (0.48,2.59)

0.7956
Thrombocytopenia

2.3 (1.27,4.19)

0.0063

2.54 (1.26,5.12)

0.0093

1.57 (0.57,4.33)

0.3791
Immunologic Anti-dsDNA

10.21 (4.34,24.05)

<.0001

2.99 (1.5,5.97)

0.0018

8.3 (2.45,28.12)

0.0007
Anti Sm

6.1 (3.39,10.97)

<.0001

4.77 (2.24,10.16)

<.0001

3.08 (1.15,8.23)

0.0247
Anti- phospholipid Anti-cardiolipin

1.58 (0.92,2.72)

0.0961

2.34 (1.21,4.51)

0.0114

1.52 (0.65,3.56)

0.3360
Anti- B2 Glycoprotein

4.71 (2.16,10.27)

0.0001

2.3 (0.73,7.2)

0.1542

2.83 (0.78,10.35)

0.1152
False positive RPR

3.08 (1.5,6.31)

0.0021

2.75 (1.2,6.28)

0.0166

4 (1.23,12.96)

0.0209
Lupus Anticoagulant

2.11 (1.2,3.72)

0.0095

2.03 (1.05,3.91)

0.0348

1.45 (0.58,3.62)

0.4246
SLE manifestation   Low C3 Only OR (CI) P Value Low C4 only OR (CI) P value Both Low C3 and Low C4 OR (CI) P value
Malar rash   0.96 (0.75,1.24) 0.7617 0.89 (0.63,1.26) 0.5172 1.29 (1.08,1.54) 0.0058
Discoid rash   1.33 (0.97,1.82) 0.0770 0.71 (0.42,1.18) 0.1826 1.3 (1.03,1.62) 0.0255*
Photosensitivity   0.68 (0.53,0.88) 0.0034 0.87 (0.62,1.24) 0.4474 0.83 (0.69,0.99) 0.0351*
Oral/Nasal Ulcers   0.68 (0.53,0.87) 0.0028 0.97 (0.69,1.38) 0.8778 0.75 (0.63,0.9) 0.0020
Arthritis   0.75 (0.57,0.98) 0.0329 1.17 (0.79,1.74) 0.4404 1.23 (1,1.5) 0.0476
Serositis Pleurisy 1.18 (0.91,1.52) 0.2131 1.03 (0.72,1.47) 0.8802 1.59 (1.32,1.9) <. 0001
Pericarditis 1.19 (0.86,1.65) 0.2914 0.82 (0.5,1.34) 0.4180 1.94 (1.56,2.41) <. 0001
Renal disorder   3.02 (1.89,4.82) <. 0001 0.99 (0.41,2.38) 0.9803 2.94 (2.02,4.28) <. 0001
Neurologic Seizures 1.19 (0.75,1.88) 0.4585 1.21 (0.65,2.24) 0.5513 1.67 (1.22,2.28) 0.0012
Psychosis 1.36 (0.66,2.8) 0.4090 1.07 (0.37,3.13) 0.9017 1.77 (1.07,2.93) 0.0272
Hematologic Hemolytic anemia 2.25 (1.37,3.7) 0.0013 1.33 (0.61,2.91) 0.4702 4.32 (3.01,6.19) <. 0001
Leukopenia 1.92 (1.49,2.49) <. 0001 1.24 (0.87,1.78) 0.2373 2.75 (2.28,3.31) <. 0001
Lymphopenia 1.38 (1.06,1.8) 0.0183 1.21 (0.83,1.75) 0.3152 2.54 (2.11,3.06) <. 0001
Thrombocytopenia 1.8 (1.3,2.51) 0.0005 1.43 (0.89,2.28) 0.1407 2.65 (2.09,3.36) <. 0001
Immunologic Anti-dsDNA 2.2 (1.7,2.85) <. 0001 2.05 (1.44,2.92) 0.0001 8.2(6.61,10.6) <. 0001
Anti Sm 2.08 (1.46,2.97) 0.0001 0.99 (0.55,1.79) 0.9744 4.23 (3.28,5.45) <. 0001
Anti- phospholipid Anticardiolipin 1.42 (1.1,1.84) 0.0076 1.64 (1.16,2.34) 0.0057 2.08 (1.73,2.5) <. 0001
Anti- b2 GP 1 1.8 (1.25,2.59) 0.0015 1.59 (0.95,2.66) 0.0791 2.2 (1.7,2.86) <. 0001
FP RPR 1.73 (1.11,2.71) 0.0162 3.93 (2.4,6.44) <. 0001 3.47 (2.53,4.76) <. 0001
Lupus anticoagulant 1.29 (0.96,1.74) 0.0920 1.33 (0.89,1.98) 0.1661 1.64 (1.33,2.02) <. 0001

Disclosure: L. Durcan, None; W. Fu, None; M. Petri, None.

To cite this abstract in AMA style:

Durcan L, Fu W, Petri M. Unresolving C4 Hypocomplementemia Associates with a Different Spectrum of Disease in SLE and Is More Important Than Transiently Low Levels [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/unresolving-c4-hypocomplementemia-associates-with-a-different-spectrum-of-disease-in-sle-and-is-more-important-than-transiently-low-levels/. Accessed .
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