Delayed-type Hypersensitivity Reaction Research Articles

Delayed drug hypersensitivity to anti-tuberculosis drug: a new desensitization scheme.

Tuberculosis is a communicable illness and one of the leading causes of death, especially in developing countries like Turkey. One of the problems that must be managed well in the treatment of tuberculosis is drug hypersensitivity. The first-line agents are very important for the success of treatment. Alternative drugs are more toxic and less successful in treatment. Therefore, it is very important to be able to include first-line drugs in the post-hypersensitivity regimen. At this point, the success of desensitization comes to the fore. There are fewer studies on rapid drug desensitization in delayed-type drug hypersensitivity to anti-tuberculosis drugs. The primary aim of the study was to determine the prevalence of delayed-type hypersensitivity reactions in drug-sensitive cases; the secondary aim was to determine the appropriate treatment management. This was a retrospective study. Demographic features, tuberculosis diagnostic indicator, clinical signs of developing a hypersensitivity reaction, reaction time, desensitization scheme and treatment were evaluated. A total of 41 tuberculosis cases were included in the study. Twenty-six of the cases were male; mean age (mean ± SD) 55.44 ±16.93 years; 70.7% of them were diagnosed bacteriologically; 70.7% of them were diagnosed with pulmonary tuberculosis. The most common skin finding was maculopapular drug eruption. The development time (mean ± SD) of the reaction in patients who developed a reaction was 34.93 ±39.62 days. The responsible agent could be identified in 15 reactions. The most common drug responsible for the reaction was rifampicin. Successful desensitization was achieved in 19 (46.3%) cases with the sensitive regimen. The duration of treatment was 8.97 ±3.44 months. When evaluated in terms of treatment results, cure and treatment completion were accepted as treatment success. In this case, 30 (73.2%) patients successfully completed the treatment. Our study is one of the largest series in which delayed-type hypersensitivity develops under tuberculosis treatment and the desensitization scheme is recommended. A practical, easy desensitization scheme had been shared in this paper.

The immunostimulatory effects of fucoidan on the cellular and humoral immune response in Wistar rats.

Natural product active ingredients are currently being studied rigorously worldwide and offer a viable substitute for traditional immunotherapy for various medical disorders. The objective of the study was to investigate the immunostimulatory properties of fucoidan in albino Wistar rats. For the current study, forty rats were divided into five groups of rats that were used in good condition. In-vivo experiments of fucoidan were carried out in Wistar albino rats, such as the cyclophosphamide-caused myelosuppression, the delayed-type hypersensitivity (DTH) response, the phagocytic activity, the haemagglutinating antibody (HA) titer, and the neutrophil adhesion test. The phagocytic index increased significantly in response to Fucoidan in a dose-dependent manner, as well as enhanced DTH reaction, and HA titer caused by sheep red blood cells sheep red blood cells. Additionally, fucoidan decreased myelosuppression in rats after cyclophosphamide treatment and enhanced neutrophil adhesion with nylon fiber. These findings imply that fucoidan has immunostimulant properties and could potentially utilised to treat immune-depression diseases.

Clinical features of allergic contact dermatitis to sandals: a case series

Background: Allergic contact dermatitis (ACD) is a skin inflammation caused by a type 4 delayed-type hypersensitivity reaction. One of the most common types of ACD is shoe dermatitis, characterized by pruritic or painful bilateral and symmetrical erythema, papules, vesicles, scaling, crusting, lichenification, or fissures at the site of footwear contact. Case series: We present seven patients with allergic contact dermatitis caused by rubber flip-flop sandals who presented with acute to chronic eczema and leukoderma. Patients range in age from 4 to 65 years old, with symptoms lasting from 5 months to 2 years. Two of the seven patients had a history of atopy. Conclusion: Flip-flop sandals are the most common offending footwear in Indonesian ACD patients because they are appropriate and comfortable in hot and humid climates like Indonesia. Rubber and rubber chemicals, preservatives, shoe adhesives, and leather materials are the most common offending allergens.

Characterization of T-Helper Immune Phenotype in Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Endorses a Delayed-Type Hypersensitivity Reaction.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug eruption with a characteristic distribution of erythema on the gluteal/inguinal region and intertriginous areas with unclear pathogenesis. In this study, we aimed to characterize the T-helper immune phenotype in SDRIFE in comparison with psoriasis and eczema to further the understanding of the pathophysiology and immune response of this rare disorder. Immunohistochemical staining was performed on 9 skin biopsies each from SDRIFE, psoriasis, and eczema using immunohistochemistry for CD3 and dual CD4/T-bet, CD4/GATA3, and CD4/RORC to quantify the percentage of Th1, Th2, and Th17 cells, respectively. A significant difference was detected in the average percentage of Th1 between all 3 groups with the highest percentage of Th1 cells seen in psoriasis, followed by SDRIFE and eczema. SDRIFE showed significantly lower Th2 expression as compared to both psoriasis and eczema. There was a trend towards a higher average percentage of Th17 in psoriasis and SDRIFE, and the ratio of Th17:Th2 was significantly higher in samples of SDRIFE compared with both eczema and psoriasis. The findings characterize SDRIFE as a Th1 and possibly Th17-driven process, which could inform future therapeutic options and substantiate the model of SDRIFE as a delayed-type hypersensitivity reaction.

Stevens-Johnson syndrome and toxic epidermal necrolysis: case series and brief literature review

Stevens-Johnson syndrome (SJS) and toxic epi- dermal necrolysis (TEN) are rare forms of delayed-type drug hypersensitivity reactions (DHRs) with extensive skin necrosis and exfoliation. Drugs are the main cause of SJS and TEN in both adults and children. The most common medications are allopurinol, aromatic antiepileptics and sulfonamides with seasonal, geographical and ethnic variations. The purpose of this paper is to present the cases of SJS/TEN which were successfully treated during the year of 2021 in our department and to provide a brief literature review.

BCG infection dose guides dendritic cell migration and T cell priming in the draining lymph node.

In contrast to delayed-type hypersensitivity (DTH) and other hallmark reactions of cell-mediated immunity that correlate with vaccine-mediated protection against Mycobacterium tuberculosis, the contribution of vaccine dose on responses that emerge early after infection in the skin with Bacille Calmette-Guérin (BCG) is not well understood. We used a mouse model of BCG skin infection to study the effect of BCG dose on the relocation of skin Dendritic cells (DCs) to draining lymph node (DLN). Mycobacterium antigen 85B-specific CD4+ P25 T cell-receptor transgenic (P25 TCRTg) cells were used to probe priming to BCG in DLN. DC migration and T cell priming were studied across BCG inocula that varied up to 100-fold (104 to 106 Colony-forming units-CFUs). In line with earlier results in guinea pigs, DTH reaction in our model correlated with BCG dose. Importantly, priming of P25 TCRTg cells in DLN also escalated in a dose-dependent manner, peaking at day 6 after infection. Similar dose-escalation effects were seen for DC migration from infected skin and the accompanying transport of BCG to the DLN. BCG-triggered upregulation of co-stimulatory molecules on migratory DCs was restricted to the first 24 hour after infection and was independent of BCG dose over a 10-fold range (105 to 106 CFUs). The dose seemed to be a determinant of the number of total skin DCs that move to the DLN. In summary, our results support the use of higher BCG doses to detect robust DC migration and T cell priming.

Polymorphic photodermatosis as a disease of failed apoptotic clearance in immune-mediated inflammation and the description of a clinical case

Polymorphic photodermatosis is the most common, acquired skin disease characterized by an abnormal, recurrent, and delayed response to sunlight.
 In this article, modern views on the etiology of pathogenesis are described clinical picture, differential diagnosis, principles of treatment and prevention of polymorphic photodermatosis. The pathogenesis of this disease is a form of delayed-type hypersensitivity reaction to photoantigens. The abnormal immune response has been attributed to the immunosuppressive effects of sunlight due to a breakdown in allergen tolerance and a disruption in the mechanisms of apoptosis.
 The main symptoms of the disease are erythema and highly itchy elements of skin lesions, which are very diverse, most often represented by macules, papules and vesicles, or vesiculo-bullous, urticarial, hemorrhagic rashes, hence the name of the disease polymorphic photodermatosis. Usually one morphology prevails in one patient. The article presents a clinical case and the results of their own observations.
 Studies of the pathogenesis of polymorphic photodermatosis have confirmed the presence of an abnormal immune response. The exact mechanism of immunosuppression caused by ultraviolet radiation and the relative contribution of UV-B and UV-A in healthy people are still unclear, but the expression of TNF-alpha, IL-4 and IL-10 and the depletion of Langerhans cells appear to be key phenomena.
 Diagnosis of the disease based on the clinical picture. The need for differential diagnosis of various forms of polymorphic photodermatosis is due to their clinical and sometimes histological similarity with other skin formations. For more accurate verification of the diagnosis, a biopsy of the examined skin area is possible, followed by histology. The histology of polymorphic photodermatosis is nonspecific, in accordance with the polymorphic clinical picture, as well as depending on the timing of the biopsy.
 Further studies of the pathological mechanisms underlying polymorphic photodermatosis may allow us to develop a more targeted approach to conservative treatment and prevention.

Safety Profile of a New Dimethylaminoethanol Derivative by Oral Administration to Laboratory Animals

A new derivative of dimethylaminoethanol, butanedioic and trans-butenedioic acids (laboratory code ADK-17) was synthesized at the Department of Organic Chemistry (Professor I.P. Yakovlev is the Head of the Department) of St. Petersburg State Chemical and Pharmaceutical University (SPCPU). This is a promising compound planned for use as an oral dosage form. In this work, we aim to evaluate manifestations of the general and specific toxicity of the new drug. Laboratory animals (white mice, rats, rabbits, guinea pigs) were used as test systems for the preclinical safety study of the new compound. Manifestations of general toxicity (acute and chronic), local irritant action, allergenic properties, immunotoxic action were studied. The reproductive toxicity of the ADK-17 drug when administered intragastrically was studied. The studied drug was found to exhibit low toxicity, cause no changes in the biochemical and morphological parameters of rats and rabbits under the conditions of course use, and have no negative effects on internal organs. When administered intragastrically in maximum doses, the drug causes no irritating effects. The use of the drug did not lead to the development of a local allergic reaction of an immediate type. Carrying out sensitization in the DTH reaction showed the absence of a sensitizing effect. The study of the immunotoxic effect of the ADK-17 drug showed that its prolonged intragastric administration for 30 days at doses of 93 and 930 mg/kg did not lead to a violation of the humoral immune response and a decrease in antibody production. Setting a delayed-type hypersensitivity reaction also confirms that the drug does not affect the development of cellular immunity. The conducted experimental studies of the drug’s reproductive toxicity in rats showed that its repeated intragastric administration at doses of 50 and 250 mg/kg to pregnant females did not have a negative effect on the reproductive system of laboratory animals, embryo- and fetotoxic, as well as teratogenic effects, having no effect on the antenatal and postnatal development of offspring.

ОЦЕНКА ИММУНОМОДУЛИРУЮЩЕЙ АКТИВНОСТИ СУХОГО ЭКСТРАКТА ТРАВЫ ТОПИНАМБУРА

. The purpose of the study was to evaluate the immunomodulatory properties of the dry extract of Jerusalem artichoke herb in terms of weight (thymus, spleen), number of cells (thymus, spleen, bone marrow) of the immune system organs, indicators of cellular and humoral immunity in mice on a model of experimental immunodeficiency induced by the cytostatic methotrexate. Materials and methods. The study of the immunomodulatory activity of the dry extract of Jerusalem artichoke herb was evaluated by the ability to restore the mass (thymus, spleen), the number of cells (thymus, spleen, bone marrow) of the immune system organs, indicators of cellular, humoral immunity and phagocytic activity of peritoneal macrophages of outbred mice under conditions of immunosuppression induced by methotrexate, to the level of intact mice, in vivo. Results. Analysis of the effect of the dry extract of Jerusalem artichoke herb in in vivo systems found that the dry extract of the herb Helianthus tuberosum L. had no effect on the mass (thymus, spleen) and the number of cells (thymus, spleen, bone marrow) of the immune system organs, the severity of the delayed-type hypersensitivity reaction, antibody production, phagocytic activity of peritoneal macrophages of intact mice and restored these parameters of the immune system in animals treated with the cytostatic methotrexate to the level of intact animals, which was comparable to the effect of the reference drug "Immunal". Conclusion. The dry extract of Jerusalem artichoke herb can be considered as a promising agent that restores the parameters of cellular, humoral immunity, the phagocytic activity of peritoneal macrophages and the cellular composition of the immune system under conditions of immunosuppression induced by methotrexate, to the level of intact animals, the effectiveness of which is comparable to the effect of the comparator drug "Immunal

Honey flower dermatitis: Contact allergy to ellagic acid in Melianthuscomosus.

A case study is reported whereby a patient with no prior allergies developed a strong and spreading delayed-type hypersensitivity reaction to Melianthus plants, nectar and synthetic pigment derived from it after frequent handling of these substances. The lesions improved after treatment with topical steroids and allergen avoidance within 1-2 weeks. Subsequent patch testing with the plants, nectar and synthetic ingredients identified ellagic acid (EA) as the sensitizing agent. This is the first proven case of allergic contact dermatitis to EA, a phenolic substance present in numerous plants, fruits, and nuts regularly consumed by humans. Melianthus use is growing worldwide as an ornamental plant. Moreover, it is used in traditional South African medicine for its anti-inflammatory effects. In recent years, these extracts and EA have been added to natural, plant-based topical formulations for the treatment of inflammatory skin disorders. Our observation that the EA found in Melianthus can induce severe contact allergy should caution for the possible dangers of specific allergic sensitizations to these increasingly used additives in natural medicines.

Study of immunotropic activity of the valine-containing neuropeptide compound of the glyprolin series under “social” stress

Aim of the study was to investigate the immunotropic activity of neuropeptide compound Pro-Gly-Pro-Val under “social” stress.Material and methods. The study was conducted on nonlinear male rats (6 months old) under conditions of “social” stress, modeled by formation of submissive and aggressive types of animal behavior under conditions of constant sensory contact. The rats were divided into groups: Control I, animals housed alone in a cage and receiving water for injection in an equivalent volume; Control II, groups of stressed animals with aggressive and submissive types of behavior; III groups of stressed rats to which Pro-Gly-Pro-Val at a dose of 100 μg/kg/day; IV groups of stressed rats to which imunofan (Arg-Asp-Lys-Val-Tyr-Arg) at an average therapeutic dose of 0.7 μg/kg/day were administered intraperitoneally. The immunotropic properties of the neuropeptide compounds were evaluated according to the following indices: delayed-type hypersensitivity reaction index, direct hemagglutination reaction antibody titer and leukocytic formula values.Results. Injection of the tested compound Pro-Gly-Pro-Val under study leads to correction of the immune changes occurring against the background of “social” stress, namely, to an increase in the delayed-type hypersensitivity reaction index and the level of anti-erythrocytic antibodies, to an enhancement in the total leukocyte count and a restoration of the percentage ratio between the form elements of the leukocytic formula. Obtained results correlate with the results of studying the immunotropic action of the comparison preparation immunofan under the conditions of “social” stress.Conclusions. The results of the study of the immunotropic action of the neuropeptide compound Pro-Gly-Pro-Val under “social” stress indicate the presence of its immunocorrective activity, which is manifested by the restoration of indices of cellular and humoral reactions and white blood cells.

Proteolipid Protein-Induced Mouse Model of Multiple Sclerosis Requires B Cell-Mediated Antigen Presentation.

The pathogenic role B cells play in multiple sclerosis is underscored by the success of B cell depletion therapies. Yet, it remains unclear how B cells contribute to disease, although it is increasingly accepted that mechanisms beyond Ab production are involved. Better understanding of pathogenic interactions between B cells and autoreactive CD4 T cells will be critical for novel therapeutics. To focus the investigation on B cell:CD4 T cell interactions invivo and invitro, we previously developed a B cell-dependent, Ab-independent experimental autoimmune encephalomyelitis (EAE) mouse model driven by a peptide encompassing the extracellular domains of myelin proteolipid protein (PLPECD). In this study, we demonstrate that B cell depletion significantly inhibited PLPECD-induced EAE disease, blunted PLPECD-elicited delayed-type hypersensitivity reactions invivo, and reduced CD4 T cell activation, proliferation, and proinflammatory cytokine production. Further, PLPECD-reactive CD4 T cells sourced from B cell-depleted donor mice failed to transfer EAE to naive recipients. Importantly, we identified B cell-mediated Ag presentation as the critical mechanism explaining B cell dependence in PLPECD-induced EAE, where bone marrow chimeric mice harboring a B cell-restricted MHC class II deficiency failed to develop EAE. B cells were ultimately observed to restimulate significantly higher Ag-specific proliferation from PLP178-191-reactive CD4 T cells compared with dendritic cells when provided PLPECD peptide in head-to-head cultures. We therefore conclude that PLPECD-induced EAE features a required pathogenic B cell-mediated Ag presentation function, providing for investigable B cell:CD4 T cell interactions in the context of autoimmune demyelinating disease.

Polyphenolics of purple devil fruits potentiate anti-inflammatory action by regulating the expression of inflammatory cytokines and apoptotic signaling molecules evident in extensive and combined experimental models

This research investigated the anti-inflammatory effects of Purple Devil fruit’s chloroform extract (SAF-CFE) using LPS-stimulated RAW264.7 macrophage cells and in-vivo histamine- and carrageenan-induced paw edema models as well as membrane stabilization model. Writhing and licking tests for nociception and delayed-type hypersensitivity reaction (DTHR) for immunomodulation were accomplished. SwissADME, ProTox-II, and PASS tests assessed a ligand-receptor binding affinity, and network-pharmacological tests explored the modulatory linked-genes. The MCF-7 cells were strongly inhibited by SAF-CFE, which reduced LPS-induced PGE2, IL-6, TNF-α, and IL-1β expression. The upregulation of proapoptotic (p53 and Bax) and downregulation of antiapoptotic (Bcl-2) genes were observed by SAF-CFE. It significantly reduced inflammatory indexes in anti-inflammatory models. Tris (2,4-di-tert-butylphenyl) phosphate, a natural biometabolite from SAF-CFE, had the highest target receptor-binding and drug-likeness; while NOS2, PTGER1, TRPV1, HMGCR, and TBXAS1 hub genes were highly modulated by the SAF-CFE. The results demonstrate that SAF-CFE could be a functional food source for anti-inflammatory action.

Modi-1, anti-citrullinated neoepitope vaccine, alone and combined with checkpoint inhibitors in patients with head and neck, breast, renal, and ovarian cancers: ModiFy phase I/II basket clinical trial—Report after completion of monotherapy dose-finding.

2566 Background: Stressful conditions in the tumor microenvironment induce autophagy, resulting in high levels of calcium in autophagosomes, in turn activating peptidylarginine deiminase enzymes; these convert arginine residues within polypeptides to citrulline and alter proteolytic cleavage. MHC-II presents these citrullinated peptides to CD4+ T cells. Modi-1 comprising three citrullinated, adjuvanted peptides targeting vimentin and enolase to inducing and expanding CD4+ T cells. At the tumor site the CD4+ T cells release proinflammatory cytokines including INFγ, further upregulating MHC class II. This enables presentation of endogenous citrullinated peptides on the tumor cells in a positive feed-forward loop. Methods: ModiFY is an open-label, multicohort, multicenter, adaptive Phase I/II basket trial for patients with unresectable Head and Neck Squamous Cell Carcinoma (SCCHN), Triple Negative Breast Cancer (TNBC), Renal Cell Carcinoma and High Grade Serous Ovarian Carcinoma (HGSOC). Patients are treated with Modi-1 alone or - if eligible for standard of care checkpoint inhibitor (CPI) monotherapy - Modi-1 + SoC CPI. The Modi-1 only expansion cohorts will recruit 16 patients per tumor type, Modi-1+CPI will recruit 21 patients per tumor type. Study objectives are safety, the breadth and strength of the cellular immune response, ORR, duration of response, PFS, and OS. Results: As of February 2023, the monotherapy dose-finding has completed. 3 patients received Mod1-1v (vimentin only) 80 µg/peptide and 3 patients received Modi-1 at 400 µg/peptide (vimentin + enolase peptides) as part of the monotherapy dose escalation. No DLTs were observed, triggering enrolment into the monotherapy expansion cohorts. 20 evaluable pts have received Modi-1v (3 pts Modi-1v 80 µg/peptide, 17 Modi-1 400 µg/peptide): 16 had HGSOC, 2 TNBC, 2 SCCHN with 53 doses received; 2 patients have been treated beyond 24 weeks. All patients had skin reactions consistent with a delayed-type hypersensitivity reaction at injection sites. Vaccinations have been well tolerated with 71 adverse reactions in 15 patients reported. All were Grade 1 or 2 except for four Grade 3 reactions in 3 patients (anemia, fatigue, and injection site reactions). There have been no SAEs. Elevation in anti-CCP antibodies has not been seen. In 13 response-evaluable patients, best overall response by RECIST v1.1 included 1 PR (SCCHN), 6 SD and 6 PD. The study is currently enrolling into the combination with checkpoint inhibition dose escalation cohorts and the monotherapy expansion cohorts. Conclusions: Modi-1 is well tolerated, and the early monotherapy efficacy data are encouraging. Safety and early efficacy data are supportive of further development of combination with CPI. Clinical trial information: NCT05329532 .

Advancing the understanding of allergic contact dermatitis: from pathophysiology to novel therapeutic approaches.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease that, especially when the condition becomes chronic, has a high impact on the quality of life and represents a significant disease burden. ACD represents a type IV delayed-type hypersensitivity reaction that is triggered by contact with an allergen in previously sensitized individuals through the activation of allergen-specific T cells. In the acute phase, it is characterized by eczematous dermatitis, which presents with erythema, edema, vesicles, scaling, and intense itch. Non-eczematous clinical forms are also described (lichenoid, bullous, and lymphomatosis). Lichenification is the most common clinical picture in the chronic phase if the culprit allergen is not found or eliminated. ACD can be associated with both occupational and non-occupational exposure to allergens, representing approximately 90% of occupational skin disorders along with irritant contact dermatitis. Patch testing with suspected allergens is required for a diagnosis. Metals, especially nickel, fragrance mix, isothiazolinones, and para-phenylenediamine, are the most commonly positive allergens in patients patch tested for suspected ACD. The treatment goal is to avoid contact with the culprit agent and use topical and/or systemic corticosteroid therapy.

Oral prednisone regulates human skin T cells in delayed-type hypersensitivity reaction elicited by diphencyprone.

The potential benefit of inducing delayed-type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders was recently reported using bulk molecular technologies. Immunophenotype of skin T cells, including cellular source of Type 1, 2, and 3 cytokines, in a local DTH reaction and their modulation by oral drugs remain to be investigated. Purified protein derivative (PPD), nickel, diphencyprone (DPCP), or house dust mite (HDM) was administered as sensitizer to 40 HVs. In addition, 20 HVs were randomized to receive oral prednisone or placebo before DPCP challenge. We characterized the immunophenotype and cytokine profile of CD3+ T cell infiltrate, and examined the modulation by oral prednisone at single cell level using multi-parameter flow cytometry and unsupervised analysis. PPD was biased towards a Th1 and Tc1 response, and HDM a Th2/Th17 and Tc2. Nickel and DPCP displayed a mixed Th1/Th2/Th17 and Tc1 response. CD4+ CD25+ FoxP3+ regulatory T cells (Tregs), the minor CD4+ CD25+ FoxP3- ICOS+ PD-1+ (activated PD-1+ Th), and CD103+ tissue resident memory (TRM) cells were detected in all groups. DPCP uniquely elicited rare CD8+ CD103+ CD25+ RoRγt+ PD-1+ ICOS+ IFNγ+ T cells (activated CD8+ IFNγ+ PD-1+ TRM). Oral prednisone decreased frequencies of activated PD-1+ Th and CD8+ IFNγ+ PD-1+ TRM subsets relative to placebo in DPCP reaction. The latter was positively correlated with improvement of clinical parameters with prednisone. DTH and skin CD3+ T cell profiles elicited by common sensitizers can be modulated by oral drugs. Corticosteroids reduce the frequencies of activated PD-1+ Th and CD8+ IFNγ+ PD-1+ TRM cells after DPCP exposure.

Heterologous effect of influenza vaccination on molluscum contagiosum infection; a case report of siblings

BackgroundMolluscum contagiosum virus (MCV) is a benign, common cutaneous infection predominantly affecting the younger pediatric population. Traditional treatments may be time consuming with variable efficacy. Time to spontaneous resolution is variable and treatment is often sought to shorten duration of infection, prevent further autoinoculation, prevent infectious spread to others and treat cosmetic intolerability.Case presentationWe present the case of two patients with complete, simultaneous clearance of their molluscum contagiosum infections after receiving a routine 2018 quadrivalent influenza vaccination. Neither patient has had recurrence of molluscum contagiosum or permanent scarring. We review trials of intralesional immunotherapy in treatment of cutaneous infections to theorize the mechanism of MCV infection clearance post influenza vaccination.ConclusionWe propose a delayed-type hypersensitivity reaction was induced as a heterologous effect of the influenza vaccination, similar to that seen in current immunotherapy treatments. This is the first reported case of MCV-directed immune reaction with infection clearance after influenza vaccination.

T-Helper 22 Cell Type Responses to Nickel in Contact Allergic Subjects Are Associated with T-Helper 1, T-Helper 2, and T-Helper 17 Cell Cytokine Profile Responses and Patch Test Reactivity

Introduction: Contact allergy to nickel (Ni) is a delayed-type hypersensitivity reaction mediated by Ni-reactive T cells producing the hallmark cytokines of several T-helper cell (Th) populations including IFN-γ (Th1), IL-4, IL-5 and IL-13 (Th2), and IL-17A (Th17). IL-22-expressing CD4+ cells, which could be either Th17 co-expressing IL-22 or Th22, expressing IL-22 in the absence of IL-17A, have also been found in Ni-provoked skin of allergic subjects. It has been unclear if Ni-reactive T cells consist of distinct Th cell type populations or if they secrete a mix of Th cell hallmark cytokines. The aim herein was to assess if cellular cytokine responses to Ni, in ex vivo-stimulated peripheral blood mononuclear cells (PBMCs) from Ni-allergic subjects, include not only Th1, Th2, and Th17 but also Th22 hallmark cytokines and to define if the cytokines are produced by distinct cell populations representing different Th profiles. Methods: PBMC from Ni-allergic subjects (n = 15) with different degrees of patch test reactivity and non-allergic controls (n = 5) were in vitro stimulated with Ni. Cytokine levels in PBMC supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA) (IFN-γ, IL-2, IL-3, IL-5, IL-6, IL-13, IL-17A, IL-22, and IL-31). FluoroSpot was used to assess if individual Ni-reactive cells produced single, or combinations of, cytokines representing different Th profiles. Cytokine combinations analyzed were IL-17A/IL-22/IFN-γ, IL-5/IL-17A/IFN-γ, IL-13/IL-22/IFN-γ, and IL-5/IL-13. Results: IL-22 as well as all other cytokines measured by ELISA were induced by Ni at higher levels in PBMC from allergic versus non-allergic subjects, with higher levels being associated with stronger patch test reactivity. The levels of most Ni-induced cytokines were positively correlated with each other; IL-2 displayed the highest correlation with other cytokines and IL-6 the lowest. FluoroSpot analysis showed that Th signature cytokines, IFN-γ (Th1), IL-5 and IL-13 (Th2), IL-17A (Th17), and IL-22 (Th22), were almost exclusively produced by distinct cell populations. Conclusion: Distinct Th cell populations, including Ni-reactive cells displaying Th1, Th2, Th17, and Th22 cytokine profiles, are all increased in PBMC from Ni-allergic subjects and positively associated with patch test reactivity. The relevance of these different Th profile populations for the up- or down-regulation of inflammatory reactions in the skin of Ni-allergic subjects remains to be clarified.

Recurrent Allergic Contact Dermatitis to Bacitracin Used in Pocket Irrigation During Breast Reconstruction Surgery.

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction that presents as a pruritic eczematous rash occurring 24 to 48 h after allergen exposure. It is a surgical complication that can impact people's quality of life after plastic surgeries. A 44-year-old female with right breast cancer presented with three recurrent episodes of severe pruritic cutaneous eczematous eruption over her right breast extending down to her trunk and vulva each time soon after her multiple breast surgeries. She was labeled as having allergies to several intravenous antibiotics received perioperatively. She was then patch tested with a positive reaction to bacitracin, a component of a modified double antibiotic solution used for pocket irrigation intraoperatively. It highlights the need for plastic surgeons to consider ACD to bacitracin in patients with dermatitis soon after having bacitracin for pocket irrigation or implant soaking during breast surgeries. Comprehensive patch testing can delineate the cause of surgery-related ACD.

Oncolytic Newcastle disease virus effects on immune response - a new issue in cancer treatment.

Millions of people are diagnosed with cancer each year, and fighting it puts a heavy financial burden on communities and governments. Numerous advances have been made in the field of cancer; one of the newest methods is using oncolytic viruses. This study aimed to evaluate the effect of oncolytic Newcastle disease virus wild-type strains (NDV-WTS) on the immune system. Forty mice were divided into four groups (10 animals in each group). The control group received phosphate buffered saline, and experimental group 1 (NDV-WTS 1), experimental group 2 (NDV-WTS 2), and experimental group 3 (NDV-WTS 3) received 10-1, 10-2, and 10-3 titers of Newcastle virus on 0, 14th, and 28th days. On the 31st day, 100 µL of Newcastle virus was injected into the left footpads of animals. After 48 hours, delayed-type hypersensitivity (DTH) reactions were measured. On the 33rd day, peritoneal macrophages were isolated. Then proliferation of the cells was measured by the methyl-thiazolyl-tetrazolium (MTT) test. Neutral red uptake and respiratory burst of peritoneal macrophages were also assessed. Data were analyzed using statistical software SPSS, version 19. The results of the DTH test showed that footpad swelling in control, NDV-WTS 1, NDV-WTS 2, and NDV-WTS 3 groups were 23.5%, 23.5%, 23.6% and 23.6%. No significant differences were seen between the groups in this regard (P > 0.05). A negative nitroblue tetrazolium (NBT) reduction test as an indicator of macrophage's respiratory burst, showed no significant difference between the groups (P > 0.05). The neutral red uptake assay and MTT test showed no significant differences between the groups (P > 0.05). The results of this study showed that NDV-WTS in doses of 10-1, 10-2, and 10-3 have no adverse effects on healthy normal cells.