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BMJ (Clinical Research Ed.) Nov 1992Passive immunisation has been used in clinical practice since the end of last century, mainly for prophylaxis. Success of early treatments was marred by anaphylactic... (Review)
Review
Passive immunisation has been used in clinical practice since the end of last century, mainly for prophylaxis. Success of early treatments was marred by anaphylactic reactions and serum sickness because antibodies or antitoxins were not raised in humans. Recombination of gene segments during antibody synthesis means that specific antibodies for numerous antigens can be produced from a limited gene pool. Killer lymphocytes, phagocytes, and complement then bind to the constant region of the antibody facilitating elimination of the pathogen. Development of a method of obtaining large quantities of antibodies against a specific antigen (monoclonal antibodies) offers the possibility of initiating host defence mechanisms against any unwanted antigen, though some problems still remain in preventing the body from attacking the monoclonal antibody.
Topics: Antibodies; Antibodies, Monoclonal; Antibody Diversity; Antibody Formation; Binding Sites, Antibody; History, 20th Century; Humans; Immunization; Immunization, Passive
PubMed: 1477573
DOI: 10.1136/bmj.305.6864.1269 -
Cureus Feb 2022Snake bites (ophidism) constitute a public health problem in tropical and subtropical countries, due to their lethality, and the lack of access to prompt treatment in...
Snake bites (ophidism) constitute a public health problem in tropical and subtropical countries, due to their lethality, and the lack of access to prompt treatment in these regions. Catastrophic consequences follow the injection of the venom due to its proteolytic, procoagulant, hemorrhagic, nephrotoxic, vasculotoxic, and myonecrotizing properties, which can lead to severe complications if not managed promptly and adequately. In this report, we present the case of a 26-year-old male patient who suffered a snake bite (Bothrops asper) on the back of his right foot. Initially, he received eight vials of antivenom and was transferred to a specialized center. However, a few hours after his arrival, a necrotic wound developed on the back of the foot along with compartment syndrome, and hence emergency fasciotomies had to be performed and the patient was admitted to the ICU for multidisciplinary management and continuous monitoring. After 14 days, fasciotomy closure and eschar incision on the dorsum of the foot were performed along with an aesthetic reconstruction with an advancement flap and full-thickness graft. The patient had a satisfactory outcome thanks to the prompt evaluation and access to a unit with experience in managing highly complex cases. Our case highlights the importance of prompt and meticulous assessment after a snake bite due to its potential for causing highly complex clinical scenarios, and early diagnosis, proper management, and continuous multidisciplinary monitoring are key for a favorable prognosis. In many cases, these bites can lead to significant tissue loss and may necessitate the amputation of the affected limb. In severe cases, compartment syndrome frequently ensues and further complicates the management and increases morbidity if not recognized and managed promptly.
PubMed: 35265431
DOI: 10.7759/cureus.21910 -
Naunyn-Schmiedeberg's Archives of... Sep 2020Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should... (Review)
Review
Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.
Topics: Adrenal Insufficiency; Contraindications, Drug; Glucocorticoids; Humans; Immunologic Factors; Mast Cells; Mastocytosis; Omalizumab; Prednisolone; Risk Assessment; Risk Factors; Serum Sickness
PubMed: 32377770
DOI: 10.1007/s00210-020-01886-2 -
Multiple Sclerosis (Houndmills,... Jan 2021Serum sickness is a type III delayed hypersensitivity reaction which causes deposition of immune-complexes in the tissues. It has been reported with rituximab, and in...
Serum sickness is a type III delayed hypersensitivity reaction which causes deposition of immune-complexes in the tissues. It has been reported with rituximab, and in this issue of the journal, there is a case report of a patient with relapsing remitting multiple sclerosis who developed a possible serum sickness after the third infusion of ocrelizumab. In this commentary, we discuss the current literature on serum sickness, and how to diagnose and manage it. We provide our opinion on this particular case, and encourage neurologists and patients to remain vigilant of such a possibility.
Topics: Antibodies, Monoclonal, Humanized; Humans; Multiple Sclerosis, Relapsing-Remitting; Rituximab; Serum Sickness
PubMed: 32427533
DOI: 10.1177/1352458520923947 -
Oncoimmunology Oct 2013Fifteen monoclonal antibodies (mAbs) are currently registered and approved for the treatment of a range of different cancers. These mAbs are specific for a limited... (Review)
Review
Fifteen monoclonal antibodies (mAbs) are currently registered and approved for the treatment of a range of different cancers. These mAbs are specific for a limited number of targets (9 in all). Four of these molecules are indeed directed against the B-lymphocyte antigen CD20; 3 against human epidermal growth factor receptor 2 (HER2 or ErbB2), 2 against the epidermal growth factor receptor (EGFR), and 1 each against epithelial cell adhesion molecule (EpCAM), CD30, CD52, vascular endothelial growth factor (VEGF), tumor necrosis factor (ligand) superfamily, member 11 (TNFSF11, best known as RANKL), and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Collectively, the mAbs provoke a wide variety of systemic and cutaneous adverse events including the full range of true hypersensitivities: Type I immediate reactions (anaphylaxis, urticaria); Type II reactions (immune thrombocytopenia, neutopenia, hemolytic anemia); Type III responses (vasculitis, serum sickness; some pulmonary adverse events); and Type IV delayed mucocutaneous reactions as well as infusion reactions/cytokine release syndrome (IRs/CRS), tumor lysis syndrome (TLS), progressive multifocal leukoencephalopathy (PML) and cardiac events. Although the term "hypersensitivity" is widely used, no common definition has been adopted within and between disciplines and the requirement of an immunological basis for a true hypersensitivity reaction is sometimes overlooked. Consequently, some drug-induced adverse events are sometimes incorrectly described as "hypersensitivities" while others that should be described are not.
PubMed: 24251081
DOI: 10.4161/onci.26333 -
Antibodies (Basel, Switzerland) Feb 2022Identification of new disease-associated biomarkers; specific targeting of such markers by monoclonal antibodies (mAbs); and application of advances in recombinant... (Review)
Review
Identification of new disease-associated biomarkers; specific targeting of such markers by monoclonal antibodies (mAbs); and application of advances in recombinant technology, including the production of humanized and fully human antibodies, has enabled many improved treatment outcomes and successful new biological treatments of some diseases previously neglected or with poor prognoses. Of the 110 mAbs preparations currently approved by the FDA and/or EMA, 46 (including 13 antibody-drug conjugates) recognizing 29 different targets are indicated for the treatment of cancers, and 66, recognizing 48 different targets, are indicated for non-cancer disorders. Despite their specific targeting with the expected accompanying reduced collateral damage for normal healthy non-involved cells, mAbs, may cause types I (anaphylaxis, urticaria), II (e.g., hemolytic anemia, possibly early-onset neutropenia), III (serum sickness, pneumonitis), and IV (Stevens-Johnson syndrome, toxic epidermal necrolysis) hypersensitivities as well as other cutaneous, pulmonary, cardiac, and liver adverse events. MAbs can provoke severe infusion reactions that resemble anaphylaxis and induce a number of systemic, potentially life-threatening syndromes with low frequency. A common feature of most of these syndromes is the release of a cascade of cytokines associated with inflammatory and immunological processes. Epidermal growth factor receptor-targeted antibodies may provoke papulopustular and mucocutaneous eruptions that are not immune-mediated.
PubMed: 35323191
DOI: 10.3390/antib11010017 -
Frontiers in Physiology 2023Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to...
Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS. 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1). There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible AMS resistant subjects ( < 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups ( < 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group ( < 0.049, interaction effect). Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS.
PubMed: 37064896
DOI: 10.3389/fphys.2023.1083808 -
Diving and Hyperbaric Medicine Dec 2020The lung is among the primary organs involved in decompression sickness (DCS). Xuebijing (XBJ), a traditional Chinese medicine, has been widely used in the treatment of...
INTRODUCTION
The lung is among the primary organs involved in decompression sickness (DCS). Xuebijing (XBJ), a traditional Chinese medicine, has been widely used in the treatment of various acute lung diseases. This study aimed to explore potential benefit of XBJ on lung injuries induced by DCS in a rabbit model.
METHODS
Twenty-four male New Zealand white rabbits underwent a simulated air dive to 50 meters' sea water for 60 min with 2.5 min decompression, and received an intravenous injection of XBJ (5 ml·kg) or an equal volume of saline immediately following decompression. DCS signs were monitored for 24 h, and blood was sampled before simulated diving and at 6 h and 12 h following decompression for determination of inflammatory indices. Lung tissues were sampled after euthanasia for histology analysis and lung water content, as well as tumour necrosis factor-α level. Another six rabbits were used as control.
RESULTS
XBJ significantly ameliorated lung injuries (lung wet/dry ratio and total protein content in bronchoalveolar lavage fluid), and notably inhibited systemic (serum level of interleukin-1β) and local (tumour necrosis factor-α in bronchoalveolar lavage fluid) inflammation responses.
CONCLUSIONS
The results strongly suggest the benefits of XBJ on ameliorating DCS lung injuries, which is possibly via inhibiting systemic and local inflammation. XBJ may be a potential candidate for the treatment of decompression-induced lung injuries.
Topics: Animals; Decompression; Decompression Sickness; Drugs, Chinese Herbal; Lung; Lung Injury; Male; Rabbits
PubMed: 33325014
DOI: 10.28920/dhm50.4.343-349 -
The Journal of Clinical Investigation Dec 2015Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and α-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment.
METHODS
We analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD(+)] and 803 without SSD [SSD(-)]) from the Données Informatisées et Validées en Transplantation data bank. Two subgroups of SSD(+) and SSD(-) patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation.
RESULTS
SSD was significantly associated with long-term graft loss (>10 years, P = 0.02). Moreover, SSD(+) patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD(-) recipients.
CONCLUSION
In conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD(+) patients.
FUNDING
This study was funded by Société d'Accélération du Transfert de Technologies Ouest Valorisation, the European FP7 "Translink" research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation.
Topics: Adult; Aged; Animals; Antilymphocyte Serum; Female; Graft Rejection; Graft Survival; Humans; Isoantibodies; Kidney; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Rabbits; Serum Sickness; Sialic Acids
PubMed: 26551683
DOI: 10.1172/JCI82267 -
Perioperative Care and Operating Room... Sep 2022Clindamycin serves as an alternative surgical prophylactic antibiotic in patients with penicillin (PCN) or cephalosporin allergy labels. In the previous reports, the use...
BACKGROUND
Clindamycin serves as an alternative surgical prophylactic antibiotic in patients with penicillin (PCN) or cephalosporin allergy labels. In the previous reports, the use of clindamycin was associated with higher incidences of surgical site infections (SSIs). We aimed to determine the characteristics of PCN or cephalosporin allergic reactions to stratify patient's risk and indicate subsequent management; leading to de-labeling of PCN or cephalosporin allergy.
METHODS
We conducted a prospective cohort study of patients receiving clindamycin as surgical antibiotic prophylaxis from September 2021 to March 2022. Data were collected from electronic medical records; included demographic data, antibiotic allergy labels, allergic reaction, and allergy testing.
RESULTS
Clindamycin was administered in 445 patients who underwent 451 operations. Among these patients, 53.0% ( = 236) were female with a median age of 15 years (range; 0.5-57.0 years). PCN and cephalosporin allergies were labelled in 83.8% ( = 373) and 25.6% ( = 114) patients, respectively; 11.4% ( = 51) of patients were allergic to both classes of the antibiotics. There were 191 (51.2%) and 73 (64.0%) possible hypersensitivity reactions (HSRs) in PCN and cephalosporin groups, respectively. The most common reactions were rash (PCN: = 99, 26.5%; cephalosporin: = 35, 30.7%), and hives (PCN: = 71, 19.0%; cephalosporin: = 24, 21.1%). Severe reactions included angioedema (PCN: = 7, 1.9%; cephalosporin: = 5, 4.4%), anaphylaxis (PCN: = 8, 2.1%; cephalosporin: = 7, 6.1%), bronchospasm (cephalosporin: = 1, 0.9%), airway involvement (PCN: = 1, 0.3%; cephalosporin: = 1, 0.9%), serum sickness (PCN: = 1, 0.3%), blisters (PCN: = 1, 0.3%), and drug reaction with eosinophilia and systemic symptoms (DRESS) (PCN: = 1, 0.3%). Low-risk history of allergy included gastrointestinal side effects (PCN: = 9, 2.4%; cephalosporin: = 3, 2.7%), positive family history (PCN: = 7, 1.9%; cephalosporin: = 1, 0.9%), and remote history of allergy (PCN: = 2, 0.5%). There were 201 (53.9%) and 53 (46.5%) unknown reactions in PCN and cephalosporin groups, respectively. In the overall cohort, 3 patients (0.7%) were skin tested for drug allergy (PCN: = 2, 0.5%; cephalosporin: = 2, 1.8%).
CONCLUSION
Clindamycin was largely administered in patients with non-severe HSRs, low-risk history or unknown reactions to PCN or cephalosporin, whom cefazolin could have been administered safely. Obtaining a detailed history of antibiotic allergy, allergy testing and/or direct oral challenge can de-label unsubstantiated PCN or cephalosporin allergy and ultimately reduce the incidence of SSIs by optimizing the rate of more effective antibiotic administration.
PubMed: 35873080
DOI: 10.1016/j.pcorm.2022.100278