Session Information
Date: Sunday, October 21, 2018
Title: Systemic Lupus Erythematosus – Clinical Poster I: Clinical Manifestations and Comorbidity
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Infection is a major cause of mortality in all stages of disease in systemic lupus erythematosus (SLE). Several risk factors for infection have been identified in SLE such as immunosuppressive medications and prednisone. Yet these do not fully explain the increased risk for infection. We have recently identified a possible association between low immunoglobulin levels and infection risk. The aim of this study was to determine whether acquired low levels of immunoglobulins (Ig) increase the risk of clinically relevant infections within two years in adults with SLE.
Methods:
SLE patients in a long term observational study are followed at 2-6 month intervals according to a standard protocol which includes demographics, clinical, laboratory and therapeutic information. Disease activity is measured by the SLEDAI-2K, and damage by the SLICC/ACR damage index (SDI). Ig are measured yearly with quantification of IgG, IgA and IgM. The Low Ig was defined as at least two consecutives or non-consecutive immunoglobulin levels below normal. Baseline was defined by the first visit when low Ig was detected. Controls were patients who never having low Ig levels. The outcome was clinically relevant infection defined as an infection requiring use of antibiotics within 2 years from baseline. Cases and controls in this cohort study were matched on age and decade and then adjusted for potential confounding using propensity score. Primary analysis was time to event using cox-regression model tested for proportional hazard assumption. Restricted cubic spline function was used to address non-linearity. Results were further confirmed using inverse probability weighted treatment (IPWT).
Results:
We identified 437 in the exposure group (221 consecutives and 227 non-consecutives) and 656 matched controls. Baseline characteristics are presented in the following table:
|
Variables at Index |
Unit |
Non-Low immunoglobulins |
Low |
P-value |
|
Disease Duration |
Mean ± SD |
7.6 ± 8.0 |
11.2 ± 9.1 |
0.0001 |
|
Ethnicity |
Black |
90 (13.7%) |
58 (13.3%) |
0.4 |
|
Caucasian |
436 (66.5%) |
292 (66.8%) |
||
|
Chinese |
57 (8.7%) |
50 (11.4%) |
||
|
Others |
73 (11.1%) |
37 (8.5%) |
||
|
SLEDAI-2K |
Mean ± SD |
5.9 ± 5.9 |
6.2 ± 6.3 |
0.02 |
|
SDI |
Mean ± SD |
0.5 ± 1.0 |
1.2 ± 1.6 |
<.001 |
|
Had Lupus Nephritis before the index. |
Yes (%) |
117 (17.8%) |
196 (44.9%) |
<.001 |
|
Proteinuria |
Yes (%) |
74 (11.3%) |
112 (25.6%) |
<.001 |
|
Any Low complement |
Yes (%) |
274 (41.8%) |
162 (37.1%) |
0.27 |
|
Increase DNA binding |
Yes (%) |
315 (48.0%) |
187 (42.8%) |
0.25 |
|
Leukopenia |
Yes (%) |
21 (3.2%) |
18 (4.1%) |
0.36 |
|
Antiphospholipids Antibodies |
Yes (%) |
168 (26.2%) |
62 (15.2%) |
0.0001 |
|
Prednisone use |
Yes (%) |
349 (53.2%) |
332 (76.0%) |
<.001 |
|
Oral Prednisone dose (mg/day) |
Mean ± SD |
15.3 ± 14.6 |
16.8 ± 16.8 |
0.06 |
|
Immunosuppressant use |
Yes (%) |
152 (23.2%) |
201 (46.0%) |
<.001 |
|
Biologics treatment |
Yes (%) |
1 (0.2%) |
5 (1.1%) |
0.10 |
All immunoglobulins showed evidence of non-linearity. Proportional hazard assumption was satisfied for immunoglobulins and propensity score. A total of 97 events (47 in exposure group and 50 in non-exposure group). IgG and IgA showed increased hazard at very low levels (1.2 g/l and 1.25 g/l respectively) after adjustment for propensity score or weighted using IPWT. All three Ig showed decreased hazard of infection for normal ranges after adjustment of propensity score.
Conclusion:
Our data suggest that very low IgG and IgA are important risk factors for infection independently from all known confounders including prednisone and immunosuppressives. Acquiring low immunoglobulins in SLE patients usually occurs later in the disease and is more likely to be seen among active patients with proteinuria and history of lupus nephritis. We recommend incorporating immunoglobulins measurement in clinical care of adult patients with SLE.
To cite this abstract in AMA style:
Almaghlouth I, Su J, Pullenayegum E, Johnson S, Gladman DD, Urowitz M. Exploring the Relation between Immunoglobulins Level and Infection Risk in Adult Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/exploring-the-relation-between-immunoglobulins-level-and-infection-risk-in-adult-patients-with-systemic-lupus-erythematosus/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/exploring-the-relation-between-immunoglobulins-level-and-infection-risk-in-adult-patients-with-systemic-lupus-erythematosus/