510 research outputs found
Long-term outcomes in corticosteroid-refractory Graves' orbitopathy treated with tocilizumab.
Up to 20% of patients with moderate to severe Graves' orbitopathy (GO) do not respond to high-dose glucocorticoids (GC). A few studies, including a randomized trial, have demonstrated the efficacy of interleukin-6 (IL-6) blockade with tocilizumab (TCZ) in GC-refractory GO. However, data on predictors of response to TCZ and long-term outcomes are lacking.
Observational single-center study on ten consecutive patients treated with TCZ for GC-refractory GO, between 2016 and 2020. Median (interquartile range) follow-up was 24 (12-36) months.
Inflammation and exophthalmos improved dramatically in all patients within months after starting TCZ. Mean Clinical Activity Score decreased from 4.80 ± 1.13 to 0.70 ± 0.82 points at 6 months (mean change: -4.10 ± 1.52; p < .0001). Proptosis improved from 23.2 ± 2.1 to 20.6 ± 2.0 mm at 6 months (mean change: -2.9 ± 1.4 mm; p < .0001). Diplopia resolved in 7 patients. Thyroid receptor antibodies decreased markedly during TCZ treatment. Baseline serum IL-6 levels did not predict clinical response. TCZ was well-tolerated. During follow-up, 3 patients were diagnosed with cancer (breast cancer in 2 and urothelial cancer in 1).
TCZ was rapidly effective and well-tolerated in our patients with GC-refractory GO. Four patients experienced mild/moderate adverse events as neutropenia, hyperlipidemia, and infections; nearly a third developed cancer during the follow-up. The increased incidence observed could be explained by the high prevalence of smokers, that are at higher risk for Graves' orbitopathy and solid malignancies as breast cancer. Thus, regular cancer screening could be proposed to this vulnerable population receiving high doses of immunosuppressants
Autoimmune Hemolytic Anemia and Pulmonary Embolism: An Association to Consider.
Autoimmune hemolytic anemia (AIHA) is increasingly recognized as a strong risk factor for venous thrombosis. However, there are currently no guidelines on thromboembolism prevention and management during AIHA. Here, we describe the case of a patient with AIHA and pulmonary embolism and resume the current knowledge on epidemiology, risk factors, treatment, and pathophysiology of thrombosis during AIHA, as well as new therapeutic perspectives to prevent thrombus formation during AIHA
Successful desensitization to pomalidomide in a patient with POEMS syndrome with delayed-type hypersensitivity to immunomodulatory imid drugs.
Vaccination recommendations for adult patients with autoimmune inflammatory rheumatic diseases
BACKGROUND: The number of individuals with autoimmune inflammatory rheumatic diseases (AIIRDs) treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and, in particular, biological therapies is also rising. The immunosuppressants, as well as the AIIRD itself, increase the risk of infection in this population. Thus, preventing infections by means of vaccination is of utmost importance. New Swiss vaccination recommendations for AIIRD patients were initiated by the Swiss Federal Office of Public Health and prepared by a working group of the Federal Commission for Vaccination Issues as well as by consultation of international experts.
METHODS: A literature search was performed in electronic databases (Cochrane, Medline, PubMed, Embase). In addition, unpublished literature was identified through a targeted website search of relevant organisations and international conferences dealing with vaccination, infectious diseases and rheumatology.
RESULTS: Although data are scarce, the following main points were retrieved from the literature. Inactivated vaccines are safe, but their immunogenicity may be reduced in AIIRD patients, especially if they are under immunosuppressive therapy. Rituximab and abatacept appear to reduce significantly immune responses after vaccination. Live vaccines are generally contraindicated under immunosuppressive therapy owing to safety concerns. Specific exceptions, as well as time intervals for the administration of live vaccines after interruption of an immunosuppressive therapy, have been formulated in this article.
CONCLUSION: More evidence regarding the immunogenicity and safety of vaccinations in AIIRD patients under various therapies is needed. Vaccination recommendations should be updated on a regular basis, as more scientific data will become available
The Fatigue Assessment Scale as a simple and reliable tool in systemic lupus erythematosus: a cross-sectional study.
The vast majority of patients with systemic lupus erythematosus (SLE) complain about fatigue. They also report fatigue as one of their most debilitating symptoms. Yet, in clinical practice, fatigue is only rarely assessed and remains poorly understood. The purpose of this study is to validate the Fatigue Assessment Scale (FAS) and assess the impact of disease activity on fatigue in SLE.
A cross-sectional single-center study of patients was included in the Swiss SLE Cohort Study. The FAS and the Short Form 36 (SF-36) were administered to SLE patients and controls with primary Sjogren's syndrome (pSS) and healthy volunteers (HV) attending our clinic. Disease activity in SLE was captured at the same time as patient-reported outcomes using the SLE Disease Activity Index score with the Safety of Estrogens in SLE National Assessment modification (SELENA-SLEDAI) and the physician's global assessment. We explored the internal consistency, reproducibility, construct validity, and convergence of the FAS, in comparison to the vitality subscale (VT) of the SF-36. We examined the association of FAS with demographics, disease type, SLE disease activity, and clinical features.
Of the 73 SLE subjects, 89% were women and 77% were Caucasians. The median age was 43 years, and 23 (32%) patients had active SLE. Demographics in pSS and HV were similar. Within the SLE group, FAS displayed good internal consistency (Cronbach's alpha = 0.93), unidimensionality, and test-retest reliability (ICC = 0.90). FAS and VT correlated well. The total FAS was highest in active SLE and pSS and higher in non-active SLE compared to HV.
The FAS is a promising tool to measure fatigue in SLE. Patients with SLE display a significantly higher level of fatigue than HV, which is even more pronounced in active disease and comparable to fatigue levels measured in pSS
Restoration of NK Cell Cytotoxic Function With Elotuzumab and Daratumumab Promotes Elimination of Circulating Plasma Cells in Patients With SLE.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by multiple cellular and molecular dysfunctions of the innate and adaptive immunity. Cytotoxic function of NK cells is compromised in patients with SLE. Herein, we characterized the phenotypic alterations of SLE NK cells in a comprehensive manner to further delineate the mechanisms underlying the cytotoxic dysfunction of SLE NK cells and identify novel potential therapeutic targets. Therefore, we examined PBMC from SLE patients and matched healthy controls by single-cell mass cytometry to assess the phenotype of NK cells. In addition, we evaluated the cell function of NK cells (degranulation and cytokine production) and the killing of B cell subpopulations in a B cell-NK cell in vitro co-culture model. We found that SLE NK cells expressed higher levels of CD38 and were not able to adequately upregulate SLAMF1 and SLAMF7 following activation. In addition, ligation of SLAMF7 with elotuzumab or of CD38 with daratumumab on SLE NK cells enhanced degranulation of both healthy and SLE NK cells and primed them to kill circulating plasma cells in an in vitro co-culture system. Overall, our data indicated that dysregulated expression of CD38, SLAMF1 and SLAMF7 on SLE NK cells is associated with an altered interplay between SLE NK cells and plasma cells, thus suggesting their contribution to the accumulation of (auto)antibody producing cells. Accordingly, targeting SLAMF7 and CD38 may represent novel therapeutic approaches in SLE by enhancing NK cell function and promoting elimination of circulating plasma cell
Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer
Bispecific T cell engagers (BiTEs), a subset of bispecific antibodies (bsAbs), can promote a targeted cancer cell’s death by bringing it close to a cytotoxic T cell. Checkpoint inhibitory T cell engagers (CiTEs) comprise a BiTE core with an added immunomodulatory protein, which serves to reverse cancer-cell immune-dampening strategies, improving efficacy. So far, protein engineering has been the main approach to generate bsAbs and CiTEs, but improved chemical methods for their generation have recently been developed. Homogeneous fragment-based bsAbs constructed from fragment antigen-binding regions (Fabs) can be generated using click chemistry. Here we describe a chemical method to generate biotin-functionalized three-protein conjugates, which include two CiTE molecules, one containing an anti-PD-1 Fab and the other containing an immunomodulatory enzyme, Salmonella typhimurium sialidase. The CiTEs’ efficacy was shown to be superior to that of the simpler BiTE scaffold, with the sialidase-containing CiTE inducing substantially enhanced T cell-mediated cytotoxicity in vitro. The chemical method described here, more generally, enables the generation of multi-protein constructs with further biological applications. [Figure not available: see fulltext.
Allergologie-immunologie - Maladies autoimmunes complexes : quand les glucocorticoïdes ne suffisent plus [Difficult to treat auto-immune diseases : when glucocorticoids are not enough]
Glucocorticosteroids (GC) remain the mainstay of treatment in most systemic inflammatory diseases. GC have a broad anti-inflammatory action of rapid onset. The downsides of prolonged GC therapy are well established and include infections, osteoporosis and metabolic adverse effects, among others. In systemic sclerosis, GC are associated with an increased risk of scleroderma renal crisis and must be avoided. Adjunction of second-line immunosuppressive drugs may improve disease control and limit GC usage. We summarize here the findings of two studies published in 2021, one reporting the benefits of combining GC with mycophenolate mofetil in immune thrombocytopenia, the other suggesting that blockage of interleukin-6 may decrease disease progression in systemic sclerosis with lung involvement
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