Category Archives: Arthritis Rheumatol

Brief Report: Menopause and Primary Ovarian Insufficiency in Women Treated for Antineutrophil Cytoplasmic Antibody-Associated Vasculitides.

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Brief Report: Menopause and Primary Ovarian Insufficiency in Women Treated for Antineutrophil Cytoplasmic Antibody-Associated Vasculitides.

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Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

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Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Arthritis Rheumatol. 2015 Jul;67(7):1922-32

Authors: Grayson PC, Carmona-Rivera C, Xu L, Lim N, Gao Z, Asare AL, Specks U, Stone JH, Seo P, Spiera RF, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Ytterberg SR, Phippard DJ, Merkel PA, Kaplan MJ, Monach PA, Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group

Abstract
OBJECTIVE: To discover biomarkers involved in the pathophysiology of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to determine whether low-density granulocytes (LDGs) contribute to gene expression signatures in AAV.
METHODS: The source of clinical data and linked biologic specimens was a randomized controlled treatment trial in AAV. RNA sequencing of whole blood from patients with AAV was performed during active disease at the baseline visit and during remission 6 months later. Gene expression was compared between patients who met versus those who did not meet the primary trial outcome of clinical remission at 6 months (responders versus nonresponders). Measurement of neutrophil-related gene expression was confirmed in peripheral blood mononuclear cells (PBMCs) to validate the findings in whole blood. A negative-selection strategy isolated LDGs from PBMC fractions.
RESULTS: Differential expression between responders (n = 77) and nonresponders (n = 35) was detected in 2,346 transcripts at the baseline visit (P < 0.05). Unsupervised hierarchical clustering demonstrated a cluster of granulocyte-related genes, including myeloperoxidase (MPO) and proteinase 3 (PR3). A granulocyte multigene composite score was significantly higher in nonresponders than in responders (P < 0.01) and during active disease than during remission (P < 0.01). This signature strongly overlapped an LDG signature identified previously in lupus (false discovery rate by gene set enrichment analysis <0.01). Transcription of PR3 measured in PBMCs was associated with active disease and treatment response (P < 0.01). LDGs isolated from patients with AAV spontaneously formed neutrophil extracellular traps containing PR3 and MPO.
CONCLUSION: In AAV, increased expression of a granulocyte gene signature is associated with disease activity and decreased response to treatment. The source of this signature is likely LDGs, a potentially pathogenic cell type in AAV.

PMID: 25891759 [PubMed – indexed for MEDLINE]

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Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody-associated vasculitis treated with glucocorticoids.

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Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody-associated vasculitis treated with glucocorticoids.

Arthritis Rheumatol. 2015 Jun;67(6):1629-36

Authors: Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Ding L, Iklé D, Villareal M, Lim N, Brunetta P, Fervenza FC, Monach PA, Stone JH, Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group

Abstract
OBJECTIVE: Nonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol.
METHODS: RAVE was a randomized, double-blind, placebo-controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper.
RESULTS: Forty-four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse-free remission over 18 months, these patients were more likely to have proteinase 3-ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener’s), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P < 0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P < 0.01).
CONCLUSION: Treatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients.

PMID: 25776953 [PubMed – indexed for MEDLINE]

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Altered cellular and humoral immunity to varicella-zoster virus in patients with autoimmune diseases.

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Altered cellular and humoral immunity to varicella-zoster virus in patients with autoimmune diseases.

Arthritis Rheumatol. 2014 Sep 15;

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Disturbed B cell homeostasis in newly diagnosed giant cell arteritis and polymyalgia rheumatica.

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Disturbed B cell homeostasis in newly diagnosed giant cell arteritis and polymyalgia rheumatica.

Arthritis Rheumatol. 2014 Jul;66(7):1927-38

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Direct and indirect rituximab-induced T cell depletion: comment on the article by Mélet et Al.

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Direct and indirect rituximab-induced T cell depletion: comment on the article by Mélet et Al.

Arthritis Rheumatol. 2014 Apr;66(4):1053

Authors: Eggleton P, Bremer E

PMID: 24757156 [PubMed – indexed for MEDLINE]

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