scholarly journals A Prospective Study of Cytomegalovirus-Specific Cell-mediated Immune Monitoring and Cytomegalovirus Infection in Patients with Active Systemic Lupus Erythematosus Receiving Immunosuppressants

2021 ◽  
Author(s):  
Jackrapong Bruminhent ◽  
Suphanan Autto ◽  
Porpon Rotjanapan ◽  
Pintip Ngamjanyaporn ◽  
Asalaysa Bushyakanist ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Immunosuppressive Therapy ◽  
Lupus Erythematosus ◽  
Active Systemic Lupus Erythematosus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Cmv Infection ◽  
Systemic Lupus

Abstract Introduction The effects of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) on CMV infection in patients with autoimmune diseases receiving immunosuppressants have not been explored. Methods Patients with active systemic lupus erythematosus (SLE) were preemptively monitored for clinically significant CMV infection (CsCMVI, defined as plasma CMV DNA loads > 3 log10 IU/mL). CMV-specific CMI was assessed using an enzyme-linked immunosorbent assay (QuantiFERON-CMV®, QF) before as well as 1 and 3 months after intense immunosuppressive therapy. Results The study included 55 patients with active SLE; patients had a mean age of 34 years (standard deviation [SD] 13 years), a median SLEDAI-2K score of 14 (SD 8), and 93% were female. Most patients had renal involvement (67%), received methylprednisolone (93%), and were CMV seropositive (95%). Thirteen (23.6%) patients developed CsCMVI. Among patients with active SLE who were QF-negative (QF–) and QF-positive (QF+) before receiving immunosuppressive therapy, 28.6% and 25% developed CsCMVI, respectively (p=0.69). However, 1 month post-immunosuppression, more QF– than QF+ patients developed CsCMVI (44.4% vs. 11.8%, p=0.03; adjusted hazard ratio 4.97 [95% confidence interval 1.07–23.10], p=0.04). Conclusions Patients with active SLE and low CMV-specific T cell responses could develop CMV infection after receiving immunosuppressants. Further studies should focus on CMV-specific CMI among patients with autoimmune diseases.

scholarly journals 2655. A Prospective Study of Cytomegalovirus Infection in Active Systemic Lupus Erythematosus Patients with Intense Immunosuppressive Therapy: Epidemiology, Associated Risk Factors, Pathogenesis, and Clinical Outcomes

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S929-S929
Author(s):  
Asalaysa Bushyakanist ◽  
Porpon Rotjanapan ◽  
Pintip Ngamjanyaporn ◽  
Tanitta Suangtamai ◽  
Jackrapong Bruminhent ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Immunosuppressive Therapy ◽  
Clinical Outcomes ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Cmv Infection ◽  
Systemic Lupus ◽  
Associated Risk Factors

Abstract Background Systemic lupus erythematosus (SLE) patients with intense immunosuppressive therapy (IT) are at higher risk for cytomegalovirus (CMV) reactivation and may develop the end-organ disease. However, the real epidemiology, associated risk factors, pathogenesis, and clinical outcomes have not been fully elucidated. Objectives To investigate the associated risk factors, possible predictors in the aspect of immunology of CMV infection and to study epidemiology, and clinical outcomes prospectively in active SLE patients within 3 months after intense IT. Methods A prospective cohort study of active SLE patients required intense IT from November 2017 to March 2019 was conducted. We collected patients’ demographics, potential risk factors, onset and presentations of CMV infection after intense IT, data on IT, cytokine panels, and flow cytometry at weeks 0, 2, 4, 8, and 12 after enrollment. Intense IT was defined as an induction therapy of active SLE disease with either the National Institute of Health or Euro-Lupus Nephritis Trial protocol regimens. Results A total of 24 patients have enrolled with a median age of 32 years old and 22/24 patients were female. Renal involvement was the most common and found in 79.2% of the patients. Median SLE disease activity index at enrollment was 14 (25%-75% interquartile range (IQR) = 8–19). At week 0, no CMV infection was documented, 91.7% of the patients had positive CMV IgG, and the median absolute lymphocyte count was 938 cells/mm3. At week 12, the median cumulative corticosteroid dose was 0.74 mg/kg/day (25%-75%IQR = 0.34–1.20) and the prevalence of CMV infection was 12.5%. Elevated interleukin-23 and tumor necrotic factor-α levels were associated with protective effect (hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02–0.58, p = 0.009 and HR 0.55, 95% CI 0.31–0.99, p = 0.049, respectively). Neurologic involvement was the independent factor that increased the risk of CMV infection (HR 0.26; 95% CI 0.08–0.79, p = 0.018). No mortality was detected. Conclusion CMV infection is common when IT is used, but only some SLE patients with intense IT develop CMV infection. Certain characteristics of the patients may assist predict future CMV infection following IT. However, further study on a larger scale is encouraged. Disclosures All authors: No reported disclosures.

scholarly journals CMV Infection Presenting as a Cavitary Lung Lesion in a Patient with Systemic Lupus Erythematosus Receiving Immunosuppressive Therapy

2009 ◽  
Vol 48 (24) ◽  
pp. 2145-2149 ◽  
Author(s):  
Naoto Azuma ◽  
Naoaki Hashimoto ◽  
Akihiro Yasumitsu ◽  
Kazuya Fukuoka ◽  
Kazunori Yokoyama ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immunosuppressive Therapy ◽  
Lupus Erythematosus ◽  
Lung Lesion ◽  
Cmv Infection ◽  
Systemic Lupus

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

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