The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus

Abstract Introduction Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value. Methods A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment. Results High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers. Conclusion Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.

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Circulating Immune Complexes and Systemic Lupus Erythematosus

Pediatric Nephrology ◽

10.1007/978-94-009-8319-9_44 ◽

1981 ◽

pp. 347-351

Author(s):

Edmund J. Lewis ◽

Jimmy L. Roberts

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Immune Complexes ◽

Circulating Immune Complexes ◽

Systemic Lupus

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Serum and Urinary Interleukin-6 in Assessment of Renal Activity in Egyptian Patients with Systemic Lupus Erythematosus

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.4137/cmamd.s32269 ◽

2016 ◽

Vol 9 ◽

pp. CMAMD.S32269 ◽

Cited By ~ 6

Author(s):

Rawhya R. EL-Shereef ◽

Ahmed Lotfi ◽

Emad A. Abdel-Naeam ◽

Heba Tawfik

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Renal Biopsy ◽

Lupus Erythematosus ◽

Interleukin 6 ◽

Control Group ◽

Strong Positive Correlation ◽

Systemic Lupus ◽

Kidney Involvement ◽

Significant Difference

Aim of the Work This study investigates whether serum and urinary interleukin-6 (IL-6) represent an early marker of kidney involvement and assesses the difference between them and renal biopsy in lupus nephritis (LN). Patients and Methods A total of 60 systemic lupus erythematosus (SLE) patients were compared to 20 healthy controls. Urinary and serum IL-6 were measured in both patients and controls. In addition, renal biopsy was done prior or shortly after urine and blood sampling; the results were classified according to the International Society of Nephrology/Renal Pathology Society classification of LN by recording the activity score and chronicity score for each sample. Results There was a significant higher level of urinary IL-6 in the SLE patients with biopsy-proven LN than in those without LN and those of the control group. However, no significant difference was reported between the three groups as regards serum IL-6. A strong positive correlation was found between urinary IL-6 and renal disease activity based on the renal SLE disease activity index (SLEDAI) score with no significant correlation regarding the extra renal SLEDAI. Urinary IL-6 was positively correlated with renal biopsy results and with its activity scores but weakly correlated with the chronicity scores. Conclusion Urinary IL-6 may provide a simple noninvasive potential marker of disease activity of renal involvement in adult patients with SLE.

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Distinct Subtypes of Microparticle-containing Immune Complexes Are Associated with Disease Activity, Damage, and Carotid Intima-media Thickness in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.160050 ◽

2016 ◽

Vol 43 (11) ◽

pp. 2019-2025 ◽

Cited By ~ 27

Author(s):

Paul R. Fortin ◽

Nathalie Cloutier ◽

Vincent Bissonnette ◽

Ellie Aghdassi ◽

Lihi Eder ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Immune Complexes ◽

Activity Index ◽

Damage Index ◽

Intima Media Thickness ◽

Vascular Damage ◽

Systemic Lupus ◽

Media Thickness

Objective.Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP.Methods.MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage.Results.We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41− MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use.Conclusion.Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.

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