-
Frontiers in Immunology 2020The glycoprotein CD2 is a costimulatory receptor expressed mainly on T and NK cells that binds to LFA3, a cell surface protein expressed on e.g., antigen-presenting... (Review)
Review
The glycoprotein CD2 is a costimulatory receptor expressed mainly on T and NK cells that binds to LFA3, a cell surface protein expressed on e.g., antigen-presenting cells. CD2 has an important role in the formation and organization of the immunological synapse that is formed between T cells and antigen-presenting cells upon cell-cell conjugation and associated intracellular signaling. CD2 expression is upregulated on memory T cells as well as activated T cells and plays an important role in activation of memory T cells despite the coexistence of several other costimulatory pathways. Anti-CD2 monoclonal antibodies have been shown to induce immune modulatory effects and clinical studies have proven the safety and efficacy of CD2-targeting biologics. Investigators have highlighted that the lack of attention to the CD2/LFA3 costimulatory pathway is a . Overall, CD2 is an attractive target for monoclonal antibodies intended for treatment of pathologies characterized by undesired T cell activation and offers an avenue to more selectively target memory T cells while favoring immune regulation.
Topics: Animals; CD2 Antigens; Humans; Immunological Synapses; Lymphocyte Activation; T-Lymphocytes
PubMed: 32582179
DOI: 10.3389/fimmu.2020.01090 -
Inflammopharmacology Jun 2023Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in... (Review)
Review
Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious role in the pathogenesis of psoriasis, in addition to specific immunological molecules such as TNF-, IL-12, IL-23, IL-17, and other molecules that can aid in the pathogenesis of psoriasis. So, during the past two decades, biologists have created chemical drugs that target these cells or molecules and therefore prevent the disease from occurring. Alefacept, efalizumab, Adalimumab, Ustekinumab, and Secukinumab are a few examples of chemical drugs. It was discovered that these chemical drugs have long-term side effects that can cause defects in the patient's body, such as the development of the rare but life-threatening disorder progressive multifocal leukoencephalopathy (PCL). Its rapidly progressive infection of the central nervous system caused by the JC virus and other drugs may cause increased production of neutralising anti-drug antibodies (ADA) and the risk of infusion reactions like pruritus, flushing, hypertension, headache, and rash. So, our context intends to talk in our review about natural products or plants that may have therapeutic characteristics for this disease and may have few or no side effects on the patient's body.
Topics: Humans; Middle Aged; Antibodies, Monoclonal; Psoriasis; Adalimumab; Interleukin-12; Inflammation
PubMed: 36995575
DOI: 10.1007/s10787-023-01178-0 -
Psoriasis (Auckland, N.Z.) 2022The quality of life in psoriatic patients is significantly impaired. Since this century, there have been biologics as a treatment for psoriasis. These biologics reduce... (Review)
Review
BACKGROUND
The quality of life in psoriatic patients is significantly impaired. Since this century, there have been biologics as a treatment for psoriasis. These biologics reduce symptoms, but more knowledge is needed about potential improvements in quality of life. As a result, biological therapy may be more valuable for patients who experience a lot of burden from their chronic skin condition in daily life. The aim of this systematic review was to investigate the possible improvement of the Dermatology Life Quality Index (DLQI) in psoriatic patients using biologics.
MATERIALS AND METHODS
An online search was performed in the PubMed database to identify relevant articles. Inclusion criteria for studies were psoriatic patients, a measurement of DLQI with biologics and without biologics. Exclusion criteria for studies were abstracts not written in English, publications before 2012, full text unavailable, quality of life measurements other than DLQI. Results from the studies with different biologics were combined into the outcome measure: ≥5 points of improvement in the DLQI score. Results of the studies in which biologics were compared with (conventional) systemic therapy were combined in the outcome measure: improvement of the DLQI score is better with biologics than with systemic therapy.
RESULTS
There were nine included articles with a total of 19.926 patients. Adalimumab, alefacept, etanercept, infliximab, ustekinumab and secukinumab were included biologics. Six studies measured the change in DLQI of different biologics in number of points. Of these six studies, 22 sub-analyses were performed and 20 of them showed a DLQI improvement of ≥5 points. The improvement in DLQI was better with biologics than with systemic therapy in two of the three measured studies.
CONCLUSION
Quality of life of psoriatic patients will be improved by the studied biologics. In the future, more research is needed into biologics on patient and quality of life characteristics.
PubMed: 35637943
DOI: 10.2147/PTT.S356568 -
JCI Insight Nov 2023Variation in the preservation of β cell function in clinical trials in type 1 diabetes (T1D) has emphasized the need to define biomarkers to predict treatment response....
Variation in the preservation of β cell function in clinical trials in type 1 diabetes (T1D) has emphasized the need to define biomarkers to predict treatment response. The T1DAL trial targeted T cells with alefacept (LFA-3-Ig) and demonstrated C-peptide preservation in approximately 30% of new-onset T1D individuals. We analyzed islet antigen-reactive (IAR) CD4+ T cells in PBMC samples collected prior to treatment from alefacept- and placebo-treated individuals using flow cytometry and single-cell RNA sequencing. IAR CD4+ T cells at baseline had heterogeneous phenotypes. Transcript profiles formed phenotypic clusters of cells along a trajectory based on increasing maturation and activation, and T cell receptor (TCR) chains showed clonal expansion. Notably, the frequency of IAR CD4+ T cells with a memory phenotype and a unique transcript profile (cluster 3) were inversely correlated with C-peptide preservation in alefacept-treated, but not placebo-treated, individuals. Cluster 3 cells had a proinflammatory phenotype characterized by expression of the transcription factor BHLHE40 and the cytokines GM-CSF and TNF-α, and shared TCR chains with effector memory-like clusters. Our results suggest IAR CD4+ T cells as a potential baseline biomarker of response to therapies targeting the CD2 pathway and warrant investigation for other T cell-related therapies.
Topics: Humans; Diabetes Mellitus, Type 1; CD4-Positive T-Lymphocytes; Alefacept; C-Peptide; Leukocytes, Mononuclear; Biomarkers; Receptors, Antigen, T-Cell
PubMed: 37751304
DOI: 10.1172/jci.insight.167881 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
Journal of Fungi (Basel, Switzerland) Mar 2021Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children... (Review)
Review
Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies.
Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated with agents that target CD2 (alefacept), CD3 (bispecific T-cell engager [BiTE] blinatumomab), CD19 (denintuzumab mafodotin, B43, BiTEs blinatumomab and DT2219ARL, the immunotoxin combotox, and chimeric antigen receptor [CAR] T-cell therapies tisagenlecleucel and axicabtagene ciloleucel), CD20 (rituximab and biosimilars, Y-ibritumomab tiuxetan, ofatumumab, and obinutuzumab), CD22 (epratuzumab, inotuzumab ozogamicin, moxetumomab pasudotox, BiTE DT2219ARL, and the immunotoxin combotox), CD25 (basiliximab and inolimomab), CD30 (brentuximab vedotin and iratumumab), CD33 (gemtuzumab ozogamicin), CD38 (daratumumab and isatuximab), CD52 (alemtuzumab), CD66b (Y-labelled BW 250/183), CD248 (ontuxizumab) and immune checkpoint inhibitors against CTLA-4 (CD152; abatacept, ipilimumab and tremelimumab) or with PD-1/PD-L1 blockade (CD279/CD274; atezolizumab, avelumab, camrelizumab, durvalumab, nivolumab and pembrolizumab). The aim of this narrative review is to describe treatment-related invasive fungal diseases (IFDs) of each category of agents. IFDs are very common in patients under blinatumomab, inotuzumab ozogamicin, basiliximab, gemtuzumab ozogamicin, alemtuzumab, and tisagenlecleucel and uncommon in patients treated with moxetumomab pasudotox, brentuximab vedotin, abatacept, ipilimumab, pembrolizumab and avelumab. Although this new era of precision medicine shows promising outcomes of targeted therapies in children with leukemia or lymphoma, the results of this review stress the necessity for ongoing surveillance and suggest the need for antifungal prophylaxis in cases where IFDs are very common complications.
PubMed: 33807678
DOI: 10.3390/jof7030186 -
Medicine Oct 2021Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common.
OBJECTIVE
To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy.
DATA SOURCES
A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment.
STUDY ELIGIBILITY CRITERIA
The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0).
RESULTS
The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18-1.86; I2 = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02-1.71; I2 = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11-2.02; I2 = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31-4.50; I2 = 0%) and etanercept (OR: 1.65; 95% CI: 1.07-2.56; I2 = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64-2.30; I2 = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89-5.44; I2 = 0%), alefacept (OR: 1.46; 95% CI: 0.20-10.47; I2 = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22-11.34; I2 = 0%) did not.
LIMITATIONS
Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors.
SYSTEMATIC REVIEW REGISTRATION NUMBER
INPLASY202110027.
Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Psoriatic; Biological Factors; Female; Herpes Zoster; Humans; Immunosuppression Therapy; Male; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 34622837
DOI: 10.1097/MD.0000000000027368 -
JCI Insight Jan 2021Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune...
Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune regulation. A better understanding of such natural mechanisms of immune regulation might identify new targets for immunotherapies that reverse type 1 diabetes (T1D). In this study, using Cox model multivariate analysis, we validated our previous findings that patients with the highest frequency of CD4+CD25+CD127hi (127-hi) cells at diagnosis experience the longest partial remission, and we showed that the 127-hi cell population is a mix of Th1- and Th2-type cells, with a significant bias toward antiinflammatory Th2-type cells. In addition, we extended these findings to show that patients with the highest frequency of 127-hi cells at diagnosis were significantly more likely to maintain β cell function. Moreover, in patients treated with alefacept in the T1DAL clinical trial, the probability of responding favorably to the antiinflammatory drug was significantly higher in those with a higher frequency of 127-hi cells at diagnosis than those with a lower 127-hi cell frequency. These data are consistent with the hypothesis that 127-hi cells maintain an antiinflammatory environment that is permissive for partial remission, β cell survival, and response to antiinflammatory immunotherapy.
Topics: Adolescent; Adult; Alefacept; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Progression; Female; Humans; Immunotherapy; Infant; Interleukin-2 Receptor alpha Subunit; Interleukin-7 Receptor alpha Subunit; Male; Multivariate Analysis; Proportional Hazards Models; T-Lymphocyte Subsets; Young Adult
PubMed: 33301420
DOI: 10.1172/jci.insight.136114 -
Diabetes Technology & Therapeutics Dec 2020Several immunotherapies have demonstrated endogenous insulin preservation in recent-onset type 1 diabetes (T1D). We considered the primary results of rituximab,...
Several immunotherapies have demonstrated endogenous insulin preservation in recent-onset type 1 diabetes (T1D). We considered the primary results of rituximab, abatacept, teplizumab, alefacept, high-dose antithymocyte globulin (ATG), low-dose ATG, and low-dose ATG ± granulocyte-colony-stimulating factor trials in an attempt to rank the effectiveness of the agents studied. C-peptide 2-h area under the curve means were modeled using analysis of covariance. The experimental treatment group effect for each study, compared with its internal control, was estimated after adjusting for baseline C-peptide and age. Percentage increase in C-peptide over placebo and the absolute difference within study were calculated to compare and contrast effect size among interventions. Low-dose ATG (55% and 103%) and teplizumab (48% and 63%) ranked highest in C-peptide preservation at 1 and 2 years, respectively. Low-dose ATG and teplizumab show the greatest impact on C-peptide preservation among recent new-onset T1D studies; these should be further explored as core immunotherapies in the T1D prevention setting.
Topics: Abatacept; Alefacept; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Granulocyte Colony-Stimulating Factor; Humans; Immunotherapy; Insulin; Insulin-Secreting Cells; Rituximab
PubMed: 32833543
DOI: 10.1089/dia.2020.0305