Optimizing conventional DMARD therapy for Sjögren's syndrome

Heijden, Eefje Hanna Martine van der; Kruize, Aike A.; Radstake, T.R.D.J.; Roon, Joël A G van

doi:10.1016/j.autrev.2018.03.003

Cited by 20 publications

(12 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite huge efforts to successfully inhibit disease activity in pSS, results of numerous clinical studies, including those testing biologicals such as rituximab, have been rather disappointing [1,39], and new promising drugs require confirmation in larger studies. Notwithstanding, treatment with, for example, Rituximab has been demonstrated to lead to biological effects, including mitigation of T and B cell activation, glandular inflammation, formation of ectopic lymphoid structures and B cell hyperactivity (reflected by reduction of serum IgG and RF) [40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Heijden

Hartgring

Kruize

et al. 2019

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

Objective: Effective treatment for primary Sjögren's syndrome (pSS) is not available. pSS immunopathology involves a variety of immune-cells and dysregulated pathways; targeting several pathways instead of only one could therefore be effective. Treatment with leflunomide (LEF) and hydroxychloroquine (HCQ) might be successful given their unique immunosuppressive properties. We aimed to study the in vitro effects of LEF, HCQ and their combination on T-and B-cell proliferation, cytokine and immunoglobulin production by activated PBMCs. Methods: PBMCs of six healthy individuals and nine pSS patients were stimulated with superantigen and TLR9 agonist to mimic the hallmark features. LEF, HCQ and their combinations were tested at clinically observed concentrations and proliferation, cytokine and immunoglobulin production were measured. Results: TCR/TLR9 activation of PBMCs induced strong proliferation of T and B-cells and production of CXCL13, IFN-α, IFN-γ, IgG and IgM. LEF dose-dependently inhibited all measured parameters, where HCQ potently and dose-dependently decreased B cell proliferation, CXCL13, IFN-α, IgG and IgM production. At different concentration combinations, HCQ and LEF inhibited several immune hallmark features more potently than each single compound. Conclusion: A combination of LEF and HCQ at clinically applicable concentrations additively inhibits immune activation, supporting a potential implementation of this drug combination in pSS treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Heijden

Hartgring

Kruize

et al. 2019

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Management of visceral manifestations linked to disease systemic activity is currently based only on rare randomized controlled trials, cohort studies or case-reports [ 334 ]. Treatment regimens are often borrowed from systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), mixed cryoglobulinemia or idiopathic organ-specific autoimmune disease management.…”

Section: Therapeuticmentioning

confidence: 99%

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

Parisis

Chivasso

Perret

et al. 2020

JCM

106

View full text Add to dashboard Cite

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3–3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the salivary glands are now known to play an active role in the pathogenesis of the disease. The aetiology of the “autoimmune epithelitis” still remains unknown, but certainly involves genetic, environmental and hormonal factors. Later during the disease evolution, the subsequent chronic activation of B cells can lead to the development of systemic manifestations or non-Hodgkin’s lymphoma. The aim of the present comprehensive review is to provide the current state of knowledge on pSS. The review addresses the clinical manifestations and complications of the disease, the diagnostic workup, the pathogenic mechanisms and the therapeutic approaches.

show abstract

“…The pathogenesis of SS is complex, but involves activated and dysregulated B lymphocytes, T cell activation and proliferation, 2,9 and to a lesser extent participation of dendritic cells, monocytes/macrophages, and natural killer (NK) cells in the inflammatory process. 2 Genetic (human leukocyte antigen [HLA] and non-HLA), [10][11][12][13][14] nongenetic factors, 1,15,16 and environmental stimuli (including viruses) 1,17,18 may trigger inflammation and B cell dysregulation.…”

Section: Pathogenesis Of Sjogren's Syndromementioning

confidence: 99%

“…Optimal treatment of SS is controversial, as a paucity of RCTs has been done. 289 Corticosteroids (CS), immunosuppressive agents (IA), 290 disease modifying antirheumatic drugs (DMARD), 2,290 and hydroxychloroquine (HCQ) [291][292][293] are often used 294 (►Table 3), but appropriate indications have not been ascertained. Unequivocal responses to systemic CS or IA have been noted in some patients with SS and extraglandular involvement.…”

Section: Corticosteroids and Immunosuppressive Agentsmentioning

confidence: 99%

“…Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by mononuclear cells (principally lymphocytes) infiltrating exocrine glands (e.g., salivary and lacrimal glands), leading to destruction of exocrine epithelial cells and dryness of mucosal surfaces. 1,2 Cardinal symptoms are dry eyes (xerophthalmia) and dry mouth (xerostomia). 1 Diverse extraglandular sites may also be affected.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

Chung

Wilgus

Fishbein

et al. 2019

Semin Respir Crit Care Med

View full text Add to dashboard Cite

Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by mononuclear cells (principally lymphocytes) infiltrating exocrine glands (e.g., salivary and lacrimal glands), leading to destruction of exocrine epithelial cells and dryness of mucosal surfaces. Cardinal symptoms are dry eyes (xerophthalmia) and dry mouth (xerostomia). Extraglandular sites are affected in 30 to 40% of cases of SS (particularly neurological, kidneys, skin, and lungs). B cell hyperactivity, autoantibody production, and hypergammaglobulinemia are cardinal features of SS. Primary SS is not associated with other autoimmune diseases. However, SS can complicate diverse autoimmune disorders (particularly systemic lupus erythematosus, rheumatoid arthritis, and scleroderma); this form is termed “secondary SS.” Pulmonary involvement is usually not a dominant feature of SS, but may be severe in some cases. In this review, we discuss specific tracheal, bronchiolar, and pulmonary complications of SS including xerotrachea, bronchiolitis, bronchiectasis, interstitial lung disease, nonspecific interstitial pneumonia, usual interstitial pneumonia, lymphoid interstitial pneumonia, organizing pneumonia, acute fibrinous and organizing pneumonia, pulmonary cysts, pleural effusions, pulmonary amyloidosis, and bronchus- or lung-associated lymphomas.

show abstract

Optimizing conventional DMARD therapy for Sjögren's syndrome

Cited by 20 publications

References 114 publications

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

Contact Info

Product

Resources

About