Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort

Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

[1]  Systemic Lupus Erythematosus Disease Activity Index , 2020, Definitions.

[2]  J. Wetterö,et al.  Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE , 2017, Lupus Science & Medicine.

[3]  Y. H. Lee,et al.  Correlation between circulating osteopontin level in systemic lupus erythematosus and disease activity and associations between osteopontin polymorphisms and disease susceptibility: A meta-analysis , 2017, Lupus.

[4]  I. Bruce,et al.  Tartrate‐Resistant Acid Phosphatase Deficiency in the Predisposition to Systemic Lupus Erythematosus , 2017, Arthritis & rheumatology.

[5]  G. Cappellano,et al.  Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases , 2016, Journal of immunology research.

[6]  N. Minato,et al.  Osteopontin in Spontaneous Germinal Centers Inhibits Apoptotic Cell Engulfment and Promotes Anti-Nuclear Antibody Production in Lupus-Prone Mice , 2016, The Journal of Immunology.

[7]  M. Petri,et al.  Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study. , 2016, Journal of proteome research.

[8]  I. Bruce,et al.  Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort , 2014, Annals of the rheumatic diseases.

[9]  A. Chiocchetti,et al.  Osteopontin circulating levels correlate with renal involvement in systemic lupus erythematosus and are lower in ACE inhibitor-treated patients , 2014, Clinical Rheumatology.

[10]  D. Elashoff,et al.  Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus , 2013, Arthritis Research & Therapy.

[11]  I. Bruce,et al.  Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort , 2012, Annals of the rheumatic diseases.

[12]  L. Rönnblom,et al.  The type I interferon system in the development of lupus. , 2011, Seminars in immunology.

[13]  F. Rieux-Laucat,et al.  Tartrate resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature , 2010, Nature Genetics.

[14]  Tom Greene,et al.  Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. , 2007, Clinical chemistry.

[15]  L. Glimcher,et al.  Osteopontin expression is essential for interferon-α production by plasmacytoid dendritic cells , 2006, Nature Immunology.

[16]  L. Pasquier,et al.  Orphanet Journal of Rare Diseases , 2006 .

[17]  L. Glimcher,et al.  Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. , 2006, Nature immunology.

[18]  C. Lam,et al.  Elevation of plasma osteopontin concentration is correlated with disease activity in patients with systemic lupus erythematosus. , 2005, Rheumatology.

[19]  L. Alfredsson,et al.  Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases , 2003, Annals of the rheumatic diseases.

[20]  M. D. de Broe,et al.  Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice. , 2003, Kidney international.

[21]  Y. Saeki,et al.  Enhanced local production of osteopontin in rheumatoid joints. , 2002, The Journal of rheumatology.

[22]  D. Gladman,et al.  Systemic lupus erythematosus disease activity index 2000. , 2002, The Journal of rheumatology.

[23]  Jorge R. Oksenberg,et al.  The Influence of the Proinflammatory Cytokine, Osteopontin, on Autoimmune Demyelinating Disease , 2001, Science.

[24]  F. Thaiss,et al.  Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis. , 2001, Kidney international.

[25]  M. Hatano,et al.  Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[26]  R. Wüthrich,et al.  Enhanced osteopontin expression and macrophage infiltration in MRL-Fas(lpr) mice with lupus nephritis. , 1998, Autoimmunity.

[27]  M. Hochberg,et al.  Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. , 1997, Arthritis and rheumatism.

[28]  D. Symmons,et al.  The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. , 1996, Arthritis and rheumatism.