The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus

Cancro, Michael P.; D’Cruz, David; Khamashta, Munther A.

doi:10.1172/jci38010

Cited by 243 publications

(175 citation statements)

References 107 publications

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“…These cumulative findings could ultimately influence incremental investigations and approaches to treatment of this morbid and heretofore inexorable lung disease. In addition to currently available regimens for treatment of antibody-mediated syndromes (25)(26)(27)(28)(29)48), the development of biologic response modifiers with specific actions at discrete, critical steps of pathologic B-cell response pathways is a very active area of ongoing research, and there is reason to believe that even more efficacious therapies will be available in the not-too-distant future (7,35,49). n…”

Section: Discussionmentioning

confidence: 99%

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

Vuga¹,

Tedrow²,

Pandit³

et al. 2014

Am J Respir Crit Care Med

168

115

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Rationale: C-X-C motif chemokine 13 (CXCL13) mediates B-cell trafficking and is increased, proportionately to disease activity, in many antibody-mediated syndromes. Dysregulated B cells have recently been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis.Objectives: To determine if CXCL13 is associated with IPF progression.Methods: CXCL13 was measured in lungs by DNA microarray and immunohistochemistry, and in plasma by ELISA.Measurements and Main Results: CXCL13 mRNA was threefold and eightfold greater in IPF lungs (n = 92) compared with chronic obstructive pulmonary disease (COPD) (n = 191) and normal (n = 108) specimens, respectively (P , 0.0001). IPF lungs also showed increased CXCL13 staining. Plasma CXCL13 concentrations (pg/ml) were greater in 95 patients with IPF (94 6 8) than in 128 subjects with COPD (53 6 9) and 57 normal subjects (35 6 3) (P , 0.0001). Circulating CXCL13 levels were highest in patients with IPF with pulmonary artery hypertension (P = 0.01) or acute exacerbations (P = 0.002). Six-month survival of patients with IPF in the highest quartile of plasma CXCL13 was 65 6 10% versus 93 6 10% in the others (hazard ratio, 5.5; 95% confidence interval, 1.8-16.9; P = 0.0008). CXCL13 increases by more than 50% in IPF serial assays, irrespective of initial values, also presaged respiratory failure (hazard ratio, 7.2; 95% confidence interval, 1.3-40.0; P = 0.008). In contrast, CXCL13 clinical associations in subjects with COPD were limited to modest correlations with FEV 1 (P = 0.05) and progression of radiographic emphysema (P = 0.05).Conclusions: CXCL13 is increased and is a prognostic biomarker in patients with IPF, and more so than in patients with COPD. This contrast indicates CXCL13 overexpressions are intrinsic to IPF, rather than an epiphenomenon of lung injury. The present data implicate CXCL13 and B cells in IPF pathogenesis, and support considerations for trials of specific B-cell-targeted therapies in patients with this intractable disease.

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Section: Discussionmentioning

confidence: 99%

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

Vuga¹,

Tedrow²,

Pandit³

et al. 2014

Am J Respir Crit Care Med

168

115

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“…Some treatments do attack the underlying inflammation, but not very effectively, and they do not dramatically alter the overall progression of the disease. But modalities to remove autoantibodies or minimize their subsequent production are already available, and several more agents are now being developed that could also work 5 . We may soon have the rationale and tools to implement novel, and potentially better, therapies for this extremely morbid and otherwise unremitting syndrome.…”

Section: Perspectivementioning

confidence: 99%

Perspective: Clues, not conclusions

Duncan

2012

Nature

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“…A crucial homeostatic cytokine for B cells that is upregulated during inflammation and accounts for the perpetuation of systemic lupus erythematosus (SLE) is the B cell activation factor BAFF [2,3]. RANTES (CCL5) is a key chemokine for T cell recruitment to inflammatory tissues and its expression is associated with renal damage [4,5].…”

Section: Introductionmentioning

confidence: 99%

Markers of childhood lupus nephritis indicating disease activity

et al. 2010

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Current treatment regimens for childhood lupus nephritis (LN) are associated with significant side-effects and toxicity in vulnerable phases of growth and development. The paucity of biomarkers particularly in childhood impedes the appropriate clinical management and the development of new therapeutics. We analyzed markers of immune system (BAFF, RANTES), complement (Bb, C1q, C3d-CIC, C5a) and endothelial cell activation (sVCAM-1) in children with LN (n=22, mean age 14.8±4.7 years), nephrotic syndrome (n =13) and age-matched healthy controls (n=20) to define parameters that correlate with LN activity. Complement fragments of the alternative (Bb, p=0.0004) classical (C3d-CIC, p<0.0001) and common pathway (C5a, p<0.0001) and the levels of BAFF (p< 0.0001), RANTES (p=0.0002) and sVCAM-1 (p=0.0004) were significantly higher in active compared to inactive LN. Activation of complement was associated with the occurrence of anti-C1q antibodies and reduced complement

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The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus

Cited by 243 publications

References 107 publications

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

Perspective: Clues, not conclusions

Markers of childhood lupus nephritis indicating disease activity

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