scholarly journals Antituberculosis Drug-induced Linear IgA Dermatosis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Nopriyati Nopriyati ◽  
Sarah Diba ◽  
Athuf Thaha ◽  
Rusmawardiana Rusmawardiana ◽  
Inda Astri Aryani ◽  
...  
Keyword(s):  
T Cells ◽  
Basement Membrane ◽  
Clinical Manifestations ◽  
Autoimmune Response ◽  
Oral Steroid ◽  
Systemic Steroid ◽  
Drug Induced ◽  
Causative Drug ◽  
Linear Iga Dermatosis ◽  
Disease Case

Introduction: Linear IgA dermatosis is a rare autoimmune vesiculobullous disease characterized by homogeneous linear IgA deposits in basement membrane of epidermis, and it can be idiopathic or drug-induced. The pathogenesis of drug-induced linear IgA dermatosis is not fully known yet, but it is associated with specific T cells. The clinical manifestations of the disease include vesiculobullous eruption, erythematous plaques, or string of pearls. Most cases still need additional therapy to avoid the expansion of the disease. Case Presentation: In this study, we present a 17-year-old male patient with erythema plaques, vesicles, and bullae with erosion in facial, oral, neck, trunk, genital, and extremities, pruritus, and burning sensation. The patient was undergoing pulmonary tuberculosis (TB) treatment for one week. Physical examination was done, and total BSA 10% and negative Asboe-Hansen sign were seen. The treatment consisted of delaying administration of TB drugs, desoximetasone cream 0.25%, cetirizine 10 mg, and aspiration of bullae. Conclusions: Drug-induced linear IgA dermatosis can occur at any age due to the administration of rifampicin and other antibiotics, angiotensin-I converting enzyme (ACE) inhibitors, or nonsteroidal anti-inflammatory drugs (NSAIDs). The drug can stimulate specific T cells that release Th2 cytokines to produce IgA antibodies against the basement membrane of epidermis. Drugs may cause an autoimmune response by cross-reaction with the target epitope, altering the conformation of epitopes, or exposing previously sequestered antigens to the immune system. The causative drug was stopped, and methyl prednisolone 0.5 - 1 mg/kg/day was given as initial therapy. In this study, we reported a rare case of a 17-year-old male with anti-TB drug-induced linear IgA dermatosis. Diagnosis was done based on clinical manifestation, histopathology, and immunofluorescence. The causative drug was stopped, the patient was given topical and systemic steroid therapy and drug desensitization. Remission was noted after six weeks of therapy, and oral steroid was slowly tapered and stopped on day 42. After stopping oral steroids, no lesions were reported. A 6-month follow-up revealed no signs of recurrence.

scholarly journals AB0345 Th9 CELLS AND THEIR ASSOCIATED CYTOKINES: THE PROBABLE PLAYERS IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND TYPE 1 DIABETES MELLITUS (T1DM)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1197.2-1198
Author(s):  
N. Mohannad ◽  
M. Moaaz ◽  
R. Mohamed Shehata
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Clinical Manifestations ◽  
Moderate Activity ◽  
Healthy Controls ◽  
Group I ◽  
Pancreatic Islets Of Langerhans ◽  
Th9 Cells ◽  
Significant Difference

Background:SLE is an autoimmune disease (AID) of unknown origin. Several factors can contribute to immune dysfunction in SLE.Interleukin 9 (IL9) is a newly emerging T cell-derived factor preferentially expressed by CD4+T cells: T helper 9 (Th9)IL9 targets different cell lineages, and can contribute to the development of allergic & AIDsWhether abnormal expression and secretion of IL9 are present in SLE patients (pts) still unidentified. It is also unclear whether IL9 exerts main proinflammatory or anti-inflammatory activities in SLE. T1DM is characterized by inflammation of the pancreatic islets of Langerhans. Insulitis progresses over time and β cells become destroyed then clinical DM is established. T1DM is regarded as a T cell-driven AIDObjectives:Evaluation of the expression of CD4+ IL9+ T cells & the level of IL9 in SLE pts compared to both healthy subjects & pts with another AID: T1DM.Also, to evaluate the correlation of these expressions with clinical features, laboratory parameters and SLE activityMethods:The study included: Group I 25 SLE pts fulfilling SLICC classification criteria divided into 2 subgroups (gps) according to SLE disease activity index (SLEDAI) IA: 20 pts with mild to moderate activity (<12) IB:5 pts with severe activity (>12) recruited from rheumatology clinic or internal medicine ward (Rheumatology unit), Main University Hospital, Alexandria. Group II 15 healthy individuals as a first control gp. Group III 15 pts with T1DM fulfilling the American Diabetes Association criteria as a second control gp. All pts were subjected to history taking, clinical examination,laboratory investigations: CBC,LFT,KFT,ESR,CRP,ANA,Anti-dsDNA,Th9 cell expression detection by flowcytometry and serum IL9 by ELISAResults:There was no statistical difference between all gps as regards age & sex but a significant increased ESR in SLE compared to controls & T1DM p< 0.001 p=0.001Th9 expression was highly increased in SLE pts, range 0.13-4.54% & mean ±SD=1.50 ± 1.47% than both control gps. In healthy controls Th9 ranged between 0.0-1.29% with mean 0.37 ±0.52%, while in T1DM pts ranged between 0.03 to 2.13% with mean of 0.67 ± 0.59%. A high significant difference was found between SLE pts and controls p=0.001, an insignificant rise was seen in SLE pts compared to T1DM pts p=0.157. A high significant increase in Th9 was found in severe SLE: mean of 3.74 ±1.15% than in pts with mild to moderate SLE: mean 0.94±0.88% p=<0.001IL9 level was highly increased in SLE pts: mean of 42.83± 23.98 pg/ml than both control gps. In healthy controls the mean was 8.54±13.27, while in T1DM with mean of 29.17±16.09 pg/ml. A high significant difference was found between SLE pts and normal controls p<0.001 but an insignificant rise with T1DM p=0.294. A high significant increase in IL9 in pts with severe ds compared to mild to moderate pts p<0.001.A significant direct correlation between Th9 & IL9 and SLEDAI/105 A significant direct correlation between damage index and Th9 p=0.040 but not IL9 p=0.053In SLE no significant relation between Th9 or IL9 & clinical manifestations or disease duration. A direct correlations between Th9 & ESR p=0.046 and CRP p=0.025,a significant correlation between IL9 and CRP p=0.033, no correlations between Th9&IL9 level and anti-dsDNA p=0.593& 0.4 Significant direct correlation between Th9 and IL9 in T1DM pts, still no correlation with glycemic profile. IL9 levels were significantly increased in SLE with elevated CRP p=0.033 & the % of Th9 cells were increased with elevated ESR and CRP p=0.025, 0.046Conclusion:In SLE pts; IL9 level and Th9 cells expression were significantly elevated compared to healthy controls. IL9 levels and the percentages of Th9 directly correlated with the SLE disease activity. IL9 levels also were significantly increased in T1DM pts compared to controls,but they were less expressed than in SLE. This suggests an important role of IL9 in the pathogenesis AIDs as SLEReferences:[1]Tahernia L et al. Cytokines in SLE: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res 2017Disclosure of Interests:None declared

T Cells: A Growing Universe of Roles in Neurodegenerative Diseases

2021 ◽  
pp. 107385842110249
Author(s):  
Dallin Dressman ◽  
Wassim Elyaman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neurodegenerative Diseases ◽  
Human Leukocyte ◽  
Autoimmune Response ◽  
Antigen Specificity ◽  
Risk Genes ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
The Central Nervous System

T cells play a central role in homeostasis and host defense against infectious diseases. T cell dysregulation can lead to recognizing self-antigens as foreign antigens, causing a detrimental autoimmune response. T cell involvement in multiple sclerosis (MS), long understood to be an autoimmune-mediated neurodegenerative disease, is well characterized. More recently, a role for T cells has also been identified for the neurodegenerative diseases Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Interestingly, several alleles and variants of human leukocyte antigen (HLA) genes have been classified as AD and PD risk genes. HLA codes for components of major histocompatibility complex (MHC) class I or class II, both of which are expressed by microglia, the innate immune cells of the central nervous system (CNS). Thus, both microglia and T cells may potentially interact in an antigen-dependent or independent fashion to shape the inflammatory cascade occurring in neurodegenerative diseases. Dissecting the antigen specificity of T cells may lead to new options for disease-modifying treatments in neurodegenerative diseases. Here, we review the current understanding of T cells in neurodegenerative diseases. We summarize the subsets of T cells, their phenotype and potential functions in animal models and in human studies of neurodegenerative diseases.

scholarly journals Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

2021 ◽  
Vol 9 (7) ◽  
pp. 1505
Author(s):  
Claire Roger ◽  
Benjamin Louart
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Clinical Manifestations ◽  
Acute Interstitial Nephritis ◽  
Convulsive Status Epilepticus ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Induced ◽  
Icu Patients

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

scholarly journals Enhancing the Nrf2 Antioxidant Signaling Provides Protection Against Trichloroethene-mediated Inflammation and Autoimmune Response

2020 ◽  
Vol 175 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Nivedita Banerjee ◽  
Hui Wang ◽  
Gangduo Wang ◽  
M Firoze Khan
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Autoimmune Response ◽  
Mediated Effects ◽  
Antioxidant Gene Expression ◽  
Responsive Element

Abstract Trichloroethene (trichloroethylene, TCE) and one of its reactive metabolites dichloroacetyl chloride (DCAC) are associated with the induction of autoimmunity in MRL+/+ mice. Although oxidative stress plays a major role in TCE-/DCAC-mediated autoimmunity, the underlying molecular mechanisms still need to be delineated. Nuclear factor (erythroid-derived 2)-like2 (Nrf2) is an oxidative stress-responsive transcription factor that binds to antioxidant responsive element (ARE) and provides protection by regulating cytoprotective and antioxidant gene expression. However, the potential of Nrf2 in the regulation of TCE-/DCAC-mediated autoimmunity is not known. This study thus focused on establishing the role of Nrf2 and consequent inflammatory responses in TCE-/DCAC-mediated autoimmunity. To achieve this, we pretreated Kupffer cells (KCs) or T cells with/without tert-butylhydroquinone (tBHQ) followed by treatment with DCAC. In both KCs and T cells, DCAC treatment significantly downregulated Nrf2 and HO-1 expression along with induction of Keap-1 and caspase-3, NF-κB (p65), TNF-α, and iNOS, whereas pretreatment of these cells with tBHQ attenuated these responses. The in vitro findings were further verified in vivo by treating female MRL+/+ mice with TCE along with/without sulforaphane. TCE exposure in mice also led to reduction in Nrf2 and HO-1 but increased phospho-NF-κB (p-p65) and iNOS along with increased anti-dsDNA antibodies. Interestingly, sulforaphane treatment led to amelioration of TCE-mediated effects, resulting in Nrf2 activation and reduction in inflammatory and autoimmune responses. Our results show that TCE/DCAC mediates an impairment in Nrf2 regulation. Attenuation of TCE-mediated autoimmunity via activation of Nrf2 supports that antioxidants sulforaphane/tBHQ could be potential therapeutic agents for autoimmune diseases.

scholarly journals Involvement of Drug-Specific T Cells in Acute Drug-Induced Interstitial Nephritis

2006 ◽  
Vol 17 (10) ◽  
pp. 2919-2927 ◽  
Author(s):  
Zoi Spanou ◽  
Monika Keller ◽  
Markus Britschgi ◽  
Nikhil Yawalkar ◽  
Thomas Fehr ◽  
...  
Keyword(s):  
T Cells ◽  
Interstitial Nephritis ◽  
Drug Induced

scholarly journals Epiligrin, a component of epithelial basement membranes, is an adhesive ligand for alpha 3 beta 1 positive T lymphocytes.

1993 ◽  
Vol 121 (5) ◽  
pp. 1141-1152 ◽  
Author(s):  
E A Wayner ◽  
S G Gil ◽  
G F Murphy ◽  
M S Wilke ◽  
W G Carter
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Basement Membrane ◽  
B Cell ◽  
Cell Lines ◽  
B Cell Lymphoma ◽  
Lymphokine Activated Killer Cells ◽  
Cutaneous Inflammation ◽  
Epidermal Basement Membrane

The cutaneous T cell lymphomas (CTCL), typified by mycosis fungoides, and several chronic T cell mediated dermatoses are characterized by the migration of T lymphocytes into the epidermis (epidermotropism). Alternatively, other types of cutaneous inflammation (malignant cutaneous B cell lymphoma, CBCL, or lymphocytoma cutis, non-malignant T or B cell type) do not show evidence of epidermotropism. This suggests that certain T lymphocyte subpopulations are able to interact with and penetrate the epidermal basement membrane. We show here that T lymphocytes derived from patients with CTCL (HUT 78 or HUT 102 cells), adhere to the detergent-insoluble extracellular matrix prepared from cultured basal keratinocytes (HFK ECM). HUT cell adhesion to HFK ECM was inhibitable with monoclonal antibodies (mAbs) directed to the alpha 3 (P1B5) or beta 1 (P4C10) integrin receptors, and could be up-regulated by an activating anti-beta 1 mAb (P4G11). An inhibitory mAb, P3H9-2, raised against keratinocytes identified epiligrin as the ligand for alpha 3 beta 1 positive T cells in HFK ECM. Interestingly, two lymphocyte populations could be clearly distinguished relative to expression of alpha 3 beta 1 by flow cytometry analysis. Lymphokine activated killer cells, alloreactive cytotoxic T cells and T cells derived from patients with CTCL expressed high levels of alpha 3 beta 1 (alpha 3 beta 1high). Non-adherent peripheral blood mononuclear cells, acute T or B lymphocytic leukemias, or non-cutaneous T or B lymphocyte cell lines expressed low levels of alpha 3 beta 1 (alpha 3 beta 1low). Resting PBL or alpha 3 beta 1low T or B cell lines did not adhere to HFK ECM or purified epiligrin. However, adhesion to epiligrin could be up-regulated by mAbs which activate the beta 1 subunit indicating that alpha 3 beta 1 activity is a function of expression and affinity. In skin derived from patients with graft-vs.-host (GVH) disease, experimentally induced delayed hypersensitivity reactions, and CTCL, the infiltrating T cells could be stained with mAbs to alpha 3 or beta 1 and were localized in close proximity to the epiligrin-containing basement membrane. Infiltrating lymphocytes in malignant cutaneous B disease (CBCL) did not express alpha 3 beta 1 by immunohistochemical techniques and did not associate with the epidermal basement membrane. The present findings clearly define a function for alpha 3 beta 1 in T cells and strongly suggest that alpha 3 beta 1 interaction with epiligrin may be involved in the pathogenesis of cutaneous inflammation.

scholarly journals Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: Implications for the initiation of the autoimmune response in multiple sclerosis

2008 ◽  
Vol 38 (5) ◽  
pp. 1297-1309 ◽  
Author(s):  
Xin Zhang ◽  
Yunan Tang ◽  
Danuta Sujkowska ◽  
Jinzhao Wang ◽  
Vinod Ramgolam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Autoimmune Response ◽  
Autoreactive T Cells

Acute Generalized Exanthematous Pustulosis With Multiple Organ Dysfunction Syndrome

2013 ◽  
Vol 22 (3) ◽  
pp. 270-273 ◽  
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Manar Al Asad ◽  
Lindsay Scratchko ◽  
Ghulam Khaleeq
Keyword(s):  
Lower Extremity ◽  
Rare Condition ◽  
Skin Condition ◽  
Multiple Organ ◽  
Drug Induced ◽  
Acute Generalized Exanthematous Pustulosis ◽  
Left Lower Extremity ◽  
Causative Drug ◽  
Diffuse Erythema ◽  
Exanthematous Pustulosis

Acute generalized exanthematous pustulosis is a rare condition characterized by sterile pustules on erythematous and edematous tissue. Mostly drug induced, this condition can also be caused by other factors. Cases due to vancomycin are rare. A 67-year-old woman with cellulitis of the left lower extremity was admitted with marked bilateral lymphedema of the lower extremities and diffuse erythema of the left lower extremity from foot to knee. She was given clindamycin and then vancomycin. On day 5, her condition worsened, with erythema involving the entire back. Although treatment with clindamycin and vancomycin was discontinued, acute generalized exanthematous pustulosis developed. After successful treatment of other complications, the skin condition improved. Because vancomycin is frequently used, clinicians should be aware of the possibility of acute generalized exanthematous pustulosis. Because the pustulosis decreases after withdrawal of the causative drug, being able to diagnose and differentiate the abnormality from other conditions is prudent.

Platelet Disorders

2015 ◽  
Author(s):  
Lawrence L K Leung ◽  
James L. Zehnder
Keyword(s):  
Platelet Function ◽  
Clinical Manifestations ◽  
Von Willebrand Disease ◽  
Drug Induced ◽  
Excessive Bleeding ◽  
Vascular Integrity ◽  
Patient Reports ◽  
Platelet Function Disorders ◽  
Hemorrhagic Disorders ◽  
Von Willebrand

A bleeding disorder may be suspected when a patient reports spontaneous or excessive bleeding or bruising, often secondary to trauma. Possible causes can vary between abnormal platelet number or function, abnormal vascular integrity, coagulation defects, fibrinolysis, or a combination thereof. This review addresses hemorrhagic disorders associated with quantitative or qualitative platelet abnormalities, such as thrombocytopenia, platelet function disorders, thrombocytosis and thrombocythemia, and vascular purpuras. Hemorrhagic dis­orders associated with abnormalities in coagulation (e.g., von Willebrand disease and hemophilia) are not covered. An algorithm shows evidence-based practice guidelines for the management of immune thrombocytopenic purpura. Tables list questions regarding bleeding and bruising to ask patients, clinical manifestations of hemorrhagic disorders, typical results of tests for hemostatic function in bleeding disorders, causes of thrombocytopenia, other forms of drug-induced thrombocytopenia, classification of platelet function disorders, and selected platelet-modifying agents. This review contains ­1 highly rendered figure, 7 tables, and 82 references. 

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