Desensitization Treatment Research Articles

Successful Desensitization With ELX/TEZ/IVA

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was given US Food and Drug Administration approval based on its therapeutic benefits to treat patients with cystic fibrosis (CF) who had at least 1 allele of the CF transmembrane conductance regulator (CFTR) with phenylalanine deleted at position 508 (F508del). The increase in genotyping studies has increased the frequency of use of CFTR modulators; however, severe allergic reactions to CFTR modulators have also been described. It is critical to avoid the offending medication and select alternative treatments while dealing with drug allergies. Drug desensitization may be taken into consideration in situations where there is no other option. This article describes home desensitization treatment for a patient with CF who developed a maculopapular rash following CFTR modulator medication. There are currently no alternative drugs for CFTR modulators, which are crucial for patients with CF, and limited experience is available with allergic reactions to these drugs. It is important to establish desensitization protocols in order to control drug reactions to CFTR modulators, which are vital for individuals with CF.

The Efficacy of Eye Movement Desensitization and Reprocessing Treatment for Depression: A Meta-Analysis and Meta-Regression of Randomized Controlled Trials.

Background: Eye Movement Desensitization and Reprocessing (EMDR) therapy has gained attention for its potential effectiveness in treating depression beyond its initial use for PTSD. This systematic review and meta-analysis aims to evaluate the efficacy of EMDR in treating depression and to identify the variables influencing its effectiveness. Methods: A comprehensive search was conducted across databases, including MEDLINE, PubMed, and EMBASE, covering studies up to January 2023. A total of 521 studies were screened, and 25 studies with 1042 participants (522 EMDR, 520 control) met the inclusion criteria and were included in the meta-analysis. The inclusion criteria involved randomized controlled trials (RCTs) comparing EMDR to control conditions such as usual care or waitlist groups, with outcomes focused on changes in depression symptoms. Results: The results show that EMDR had a significant effect on reducing depression symptoms (Hedges' g = 0.75), with moderate heterogeneity being observed. The meta-regression indicated that the severity of depression was a significant predictor of EMDR's effectiveness, with greater effects in severe cases. Additionally, the systematic review analyzed and evaluated various theoretical models and related studies that explain how EMDR works for the treatment of depression, reporting on neurobiological models proposed in previous research. Conclusions: This study confirms that EMDR is effective in treating depression, particularly in severe cases, and highlights its potential as a non-pharmacological intervention. However, this study highlights the need for more standardized research and long-term evaluations to assess EMDR's lasting impact. Integrating EMDR into multimodal treatment plans and primary care, especially for treatment-resistant depression, could significantly improve patient outcomes.

Spleen aminopeptides (FUKETUO) elevate the therapeutic effect of house dust mite desensitization on allergic asthma by inducing interleukin-10 positive regulatory T cells (IL-10+ Tregs) expression.

As a novel immunomodulator, spleen aminopeptides (FUKETUO) can correct the imbalance of immune cells and elevate their functions. Spleen aminopeptides have been used in the treatment of respiratory diseases. However, the regulatory mechanism of it on allergic asthma and desensitization has not been reported, further study is critically needed. This study aimed to investigate the effect and mechanism of spleen aminopeptides on allergic asthma and desensitization. We established an allergic asthma model by house dust mite (HDM) with/without desensitization treatment. The allergic asthma mouse model was established with HDM and treated with desensitization and increasing dose of spleen aminopeptides according to different immune phases. Pathological markers such as airway hyper-responsiveness, and cell composition were monitored to determine the effectiveness of treatment. Spleen aminopeptides can promote the proportion of interleukin-10 positive (IL10+) allergen-specific regulatory T cells (Tregs), and further promote interleukin-10 (IL-10) expression in desensitization. They alleviated the allergic symptoms and elevated desensitization, decreased airway hyper-reaction and lung tissue injury, reduced specific immunoglobulin E (IgE) in serum, eosinophil number and interleukin-4 (IL-4) expression in bronchoalveolar lavage fluid (BALF), therefore, being able to control allergic asthma. Our results suggested that spleen aminopeptides (FUKETUO) could elevate the expression of (CD4+CD25+IL10+) Tregs, especially when it co-immunized with desensitization. Thereby, FUKETUO improved the efficacy of desensitization, and inhibited the development of allergic asthma.

Desensitization treatment in MIH-affected teeth: a systematic review.

The present systematic review aims to summarize the current evidence regarding various treatment modalities and their results when dealing with hypersensitivity in teeth with Molar-Incisor Hypomineralization (MIH). Systematic searches were conducted in PubMed and Scopus using the search terms "MIH AND Hypersensitivity AND treatment." Studies involving children aged 6-18years diagnosed with MIH and exhibiting hypersensitivity were considered for inclusion. The outcomes examined included clinical, behavioral, and psychosocial treatment options for reducing hypersensitivity. A meta-analysis was performed for six of the included articles, and the I2 value was calculated to determine heterogeneity. A total of eight articles met the inclusion criteria for this review, with six eligible for the meta-analysis. Various treatment modalities, such as dental mousse, sealing, laser therapy, and crown therapy, demonstrated significant reductions in hypersensitivity individually (p < 0.05). The treatment methods that offer the most effective reduction in hypersensitivity are sealing with resin composite or glass ionomer cement for mild cases of MIH, while crown therapy is more effective for severe cases of MIH. However, the small number of participants and short follow-up times limit the strength of these conclusions.

A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

Educational Implications: Physiological Changes in Eye Movement Desensitization and Reprocessing Treatment for Post-Traumatic Stress Disorder

Despite more than three decades of research, the educational community's understanding of the mechanisms underlying Eye Movement Desensitization and Reprocessing treatment remains incomplete. This article critically examines the existing literature, focusing on the physiological mechanisms present when Eye Movement Desensitization and Reprocessing therapy is successfully administered. The review encompasses various research methodologies, including neuroimaging investigations tracking volumetric changes, shifts in relative brain activity across regions, and electroencephalographical alterations in brain function. Through this exploration, the authors underscore the necessity for future studies that delve into the mechanisms of action within children and adolescents and the transformations associated with treating complex post-traumatic stress disorder. The article will identify gaps in knowledge, emphasizing implications for educators and educational practices. A deeper understanding of these phenomena will provide insights for educators and the approaches used to address trauma-related issues in educational settings.

Eye movements desensitization and reprocessing with finger movements and Elite mobile health software on guilt feeling of parents of children with autism: A randomized trial.

INTRODUCTION: Caring for an autistic child at home can be challenging for parents, as it can make it difficult to balance their responsibilities. This imbalance can negatively affect the emotional well-being of the caregiver and lead to feelings of guilt. While this is a known issue, there may be gaps in knowledge specific to Iran. In this study, a new method was introduced to address this issue. This study aimed to examine the impact of desensitization with eye movements and reprocessing (EMDR) on reducing parental guilt among autistic children's families. We aim to examine the effectiveness of two different treatment methods. This study involved 90 parents (60 mothers, 30 fathers) of autistic children randomly assigned to either an experimental or control group. The two experimental groups received a 45-min intervention session once a week for 3 weeks, while the control group did not receive any intervention. Data on feelings of guilt was collected using a questionnaire. After 30 days, both groups took a follow-up test. The data were analysed using statistical software. This study found that there were significant differences in guilt feelings among different groups of EMDR therapy and a control group. Specifically, no significant differences were observed in the mean guilt scores between the experimental and control groups at the pre-intervention stage (p > .05). However, the experimental groups exhibited significantly lower mean guilt scores immediately after the intervention and 1 month later than the control group (p < .05). Immediately after the intervention and 1 month later, no significant differences were observed between the two experimental groups (p > .05). The findings of this study demonstrate the efficacy of desensitization treatment using eye movements and reprocessing in reducing feelings of guilt among autistic children's parents. In the follow-up phase, it seems that the two-way stimulation method with finger movements is more effective than Elite software in terms of the continuity of the effect. Healthcare providers are encouraged to learn and use these methods to help prevent and treat psychological issues in autistic children.

Functional characterization of complete and immunodominant epitopes of a novel pollen allergen from Parthenium hysterophorus.

Background. Parthenium hysterophorus pollen induces chronic clinical conditions such as allergic rhinitis and bronchial asthma. Among the plethora of proteins in the pollens, only few were reported to induce allergy. Currently sensitization to P. hysterophorus pollen allergen is diagnosed by skin prick test (SPT) using the entire pollen extract instead of using the specific allergen. Methods. In P. hysterophorus sensitized patients, SPT was done using the crude pollen extract, 40 kDa allergenic pollen protein and two commercially synthesized allergen epitopes (17 and 24) of P. hysterophorus. Dot-blot of allergen epitopes was done using P. hysterophorus sensitized sera. Crude pollen extract (1, 1.25, 2.5, 5 and 10 µg/mL), 40 kDa allergenic protein (3 µg/mL), and allergen epitopes (3µg/mL) were used to perform Basophil Activation Test (BAT). Results. Crude pollen extract at 2.5, 5, 10 μg/mL and 40 kDa allergenic protein at 3μg/mL concentrations induced wheal and flare reaction by around 15 minutes, whereas commercially synthesized allergen epitopes at 3μg/mL induced wheal and flare reactions in less than 10 minutes. Allergen epitopes (3 µg/mL) revealed strong reactivity with sensitized patient's IgE in dot-blot analysis. Basophil activation Test using crude pollen extract (2.5, 5, 10 µg/mL), 40 kDa allergenic protein (3 µg/mL), and allergenic epitopes (3µg/mL) indicated significant basophil activation (as measured by CD63 expression) in sensitized patients. Conclusions. The 40 kDa allergenic protein and its allergenic epitopes (17 and 24) induced phenotypic and cellular immune responses in P. hysterophorus sensitized individuals. The tested allergenic epitopes (17 and 24) induced faster wheal and flare reactions in comparison with the crude extract and the 40 kDa allergenic protein. The novel 40kDa allergenic protein and its allergen epitopes identified here may be useful for the development of component-resolved diagnosis (CRD) while also serving as a potential therapeutic lead for desensitization treatment for P. hysterophorus pollen induced allergy.

The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation

Objective: To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured. Results: After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) (P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) (P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0-15 989) (P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 (P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions: The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Comparison of estimated blood loss during living kidney transplantation according to the number of double-filtration plasmapheresis

BackgroundPlasmapheresis is an important preoperative desensitization treatment for ABO-incompatible living kidney transplantation. However, in cases with plasma exchange therapy (PET), it is necessary to consider the risks of perioperative bleeding and healthcare economic costs. This study investigated the association between intraoperative blood loss and the frequency of preoperative double-filtration plasmapheresis (DFPP) and explored the correlation between DFPP frequency and coagulation factors. Furthermore, the study examined the incidence of perioperative bleeding complications.MethodsWe enrolled 294 patients (205 men and 89 women) who underwent living kidney transplantation at our institution between January 2020 and March 2023, without PET or with only DFPP performed as PET. A single dose of rituximab (200 mg) was administered to ABO-incompatible living kidney transplant patients within 7 days before transplantation. In these patients, PET was performed until anti-blood group IgG and IgM antibody titers were reduced to 32 times or less.ResultsThe intraoperative blood loss increased in accordance with the DFPP sessions. The amount of bleeding significantly increased when DFPP was performed ≥ 2 sessions. Considering this, we initiated serum fibrinogen level measurements from the middle of the study and observed that serum fibrinogen levels decreased in correlation with the number of DFPP sessions. Fibrinogen levels dropped to critical levels (< 100 mg/dL) after three sessions of DFPP. Within the entire cohort, four patients (1.4%) underwent post-transplantation hematoma removal surgery, and among them, three had received DFPP before transplantation.ConclusionsThe number of DFPP procedures was associated with the amount of bleeding and serum fibrinogen levels during living kidney transplantation.

Mid-term efficacy evaluation of ABO incompatible living relative kidney transplantation based on protocol biopsy

Objective: To evaluate the mid-term efficacy of ABO incompatible living donor kidney transplantation (ABOi-KT) based on the results of routine renal biopsy for transplantation. Methods: Retrospective collection of clinical data from 23 pairs of ABOi-KT donors and recipients at the First Affiliated Hospital of Sun Yat-sen University from July 2015 to November 2021. ABOi-KT was performed on recipients after desensitization treatment, and the results of routine kidney transplant biopsy at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were analyzed. Combined with blood type antibody levels and renal function recovery, the mid-term efficacy of ABOi-KT was evaluated. Results: Among the 23 recipients, there were 19 males and 4 females; age range from 19 to 47 years old [(29.6±6.7) years old], all underwent ABOi-KT successfully after receiving desensitization treatment. The follow-up time was (44.6±22.4) months, of which 22 cases were followed up for more than 1 year. The incidence rates of rejection reactions at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were 15.0% (3/20), 11.1% (1/9), 7.7% (1/13), 25.0% (3/12), and 12.5% (1/8), respectively. For receptors with rejection reactions, targeted anti-rejection therapy was performed based on clinical symptoms and various indicators. Borderline T cell mediated rejection (TCMR) can be converted to mild tubular inflammation after anti-rejection treatment. The positive rate of complement C4d in peritubular capillaries was 95.0% (19/20) one week after surgery, and the positive rate of complement C4d was 100% at 3 and 12 months after surgery. The cumulative survival rates at 1, 3, 5, and 7 years after surgery were all 100%. The cumulative survival rates at 1, 3, 5, and 7 years after kidney transplantation were 100%, 93.3%, 84.0%, and 84.0%, respectively. Except for 2 recipients who underwent transplantation in 2017 and experienced kidney failure at 30 and 49 months after surgery, all other transplanted kidneys survived. Conclusions: The results of routine renal transplant biopsy show that ABOi-KT has a good mid-term therapeutic effect. The pathological changes of ABOi-KT can be dynamically observed through routine renal transplant biopsy and targeted treatment for rejection reactions can be provided accordingly.

Is a Personal Trauma History a Risk Factor for the Development of Secondary Traumatization in EMDR Therapists?

Symptoms severe enough to constitute a secondary traumatization (ST) can arise from providing eye movement desensitization and reprocessing (EMDR) treatment. However, little is known about specific risk factors such as a personal trauma history. EMDR therapists (n= 115) filled out a questionnaire battery to test whether the personal trauma history predicts symptom levels over and beyond vicarious exposure and whether vicarious exposure mediates the relationship between primary trauma history and current ST severity. Current exposure predicts ST symptom severity, while lifetime exposure is negatively associated. The number of primary traumata and the total severity of primary traumata do not explain additional variance in ST symptom severity. The mediation model suggests that primary trauma exposure instead is associated with treating more traumatized clients. The current results suggest that ST is a relevant topic to address in EMDR training, but the personal trauma history does not seem to constitute a relevant risk factor per se. It might, however, be associated with preferences for clientele composition, which in turn might act as a risk factor.

Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study.

Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre-existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620-18,282) mg, and the mean number of doses was 14 (4-63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Higher Donor Age and Severe Microvascular Inflammation Are Risk Factors for Chronic Rejection After Treatment of Active Antibody-Mediated Rejection.

Recent developments in intensive desensitization protocols have enabled kidney transplantation in human leukocyte antigen (HLA)-sensitized recipients. However, cases of active antibody-mediated rejection (AABMR), when they occur, are difficult to manage, graft failure being the worst-case scenario. We aimed to assess the impact of our desensitization and AABMR treatment regimen and identify risk factors for disease progression. Among 849 patients who underwent living-donor kidney transplantation between 2014 and 2021 at our institution, 59 were diagnosed with AABMR within 1year after transplantation. All patients received combination therapy consisting of steroid pulse therapy, intravenous immunoglobulin, rituximab, and plasmapheresis. Multivariable analysis revealed unrelated donors and preformed donor-specific antibodies as independent risk factors for AABMR. Five-year death-censored graft survival rate was not significantly different between patients with and without AABMR although 27 of 59 patients with AABMR developed chronic AABMR (CABMR) during the study period. Multivariate Cox proportional hazard regression analysis revealed that a donor age greater than 59years and microvascular inflammation (MVI) score (g + ptc) ≥4 at AABMR diagnosis were independent risk factors for CABMR. Our combination therapy ameliorated AABMR; however, further treatment options should be considered to prevent CABMR, especially in patients with old donors and severe MVI.

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data.

The number of sensitized heart failure patients on waiting lists for heart transplantation (HTx) is increasing. Using the Korean Organ Transplantation Registry (KOTRY), a nationwide multicenter database, we investigated the prevalence and clinical impact of calculated panel-reactive antibody (cPRA) in patients undergoing HTx. We retrospectively reviewed 813 patients who underwent HTx between 2014 and 2021. Patients were grouped according to peak PRA level as group A: patients with cPRA ≤10% (n= 492); group B: patients with cPRA >10%, <50% (n=160); group C patients with cPRA ≥50% (n=161). Post-HTx outcomes were freedom from antibody-mediated rejection (AMR), acute cellular rejection, coronary allograft vasculopathy, and all-cause mortality. The median follow-up duration was 44 (19-72) months. Female sex, re-transplantation, and pre-HTx renal replacement therapy were independently associated with an increased risk of sensitization (cPRA ≥50%). Group C patients were more likely to have longer hospital stays and to use anti-thymocyte globulin as an induction agent compared to groups A and B. Significantly more patients in group C had positive flow cytometric crossmatch and had a higher incidence of preformed donor-specific antibody (DSA) compared to groups A and B. During follow-up, group C had a significantly higher rate of AMR, but the overall survival rate was comparable to that of groups A and B. In a subgroup analysis of group C, post-transplant survival was comparable despite higher preformed DSA in a desensitized group compared to the non-desensitized group. Patients with cPRA ≥50% had significantly higher incidence of preformed DSA and lower freedom from AMR, but post-HTx survival rates were similar to those with cPRA <50%. Our findings suggest that sensitized patients can attain comparable post-transplant survival to non-sensitized patients when treated with optimal desensitization treatment and therapeutic intervention.

Aluminum hydroxide nanoparticle adjuvants can reduce the inflammatory response more efficiently in a mouse model of allergic asthma than traditional aluminum hydroxide adjuvants.

Traditional aluminum hydroxide is widely used as a vaccine adjuvant. Despite its favorable safety profile, it can cause an inflammatory response at the injection sites. However, multiple studies have shown that aluminum hydroxide nanoparticles have more potent adjuvant activity than their traditional aluminum hydroxide counterparts as antigen carriers; it has also been found that the local inflammation caused by aluminum hydroxide nanoparticle adjuvants is milder than that of other adjuvants. The aim of the present study was to compare the degree of inflammatory response between the aluminum hydroxide nanoparticle adjuvants and the traditional aluminum hydroxide adjuvants in the desensitization treatment of a mouse model of house dust mite (HDM)-induced allergic asthma. Mice were sensitized intraperitoneally with HDM. Subcutaneous desensitization was performed with PBS, traditional aluminum hydroxide adjuvants and aluminum hydroxide nanoparticle adjuvants. The mice were challenged and subsequently euthanized. The skin tissue at the local injection sites was assessed and specific indices were measured, such as the response of specific immunoglobulins, the airway hyper-responsiveness (AHR), and the inflammation in the bronchoalveolar lavage and lung tissues. Early hypersensitivity responses were suppressed in mice treated with subcutaneous immunotherapy (SCIT). Both traditional aluminum hydroxide-SCIT and aluminum hydroxide nanoparticle-SCIT could inhibit AHR. However, aluminum hydroxide nanoparticle-SCIT was able to significantly inhibit the secretion of eosinophils in the lung tissue and the production of type 2 cytokine Interleukin (IL)-5 in blood compared with the corresponding effects noted by traditional aluminum hydroxide adjuvants. Moreover, the aluminum hydroxide nanoparticle group reduced the inflammatory response at the local injection site. Collectively, the data indicated that allergen-specific immunotherapy using aluminum hydroxide nanoparticle adjuvants reduces lung and local inflammation compared with traditional aluminum hydroxide adjuvants.

Alloantibody Levels, Immunoglobulin Degradation Products, and Platelet Transfusion Response over Successful Desensitization of Severe Alloimmune Platelet Refractoriness with a Novel IgG-Targeted Enzyme Therapeutic

INTRODUCTION Alloimmune platelet refractoriness (APR), an insufficient response to platelet transfusion due to anti-HLA alloantibodies, affects ~25% of acute myeloid leukemia (AML) patients. In APR, HLA- or crossmatch-compatible platelet units may not be identifiable, precluding transfusion and increasing hemorrhage risk. Single antigen bead testing (SAB) semi-quantitates antibody levels against cognate HLA antigens in units of mean fluorescence intensity (MFI). MFI &amp;gt;3,000 suggests an incompatible platelet antigen for transfusion. Imlifidase, an IgG-specific cysteine protease, cleaves IgG first into single-cleaved IgG (scIgG) with limited Fc-mediated function, then into inactive F(ab') fragments 1. We previously reported successful desensitization and provision of permissive platelet transfusions in an APR patient following desensitization treatment with imlifidase. Here we report pre- and post-desensitization alloantibody (PDAb) levels in correlation with IgG degradation products and response to single donor platelet transfusion. CASE As described previously 2, a 43-year-old highly sensitized (calculated PRA [cPRA] 99.9%) woman with AML and history of life-threatening thrombocytopenic hemorrhage secondary to APR presented for matched-unrelated donor stem cell transplantation. Nationwide, few compatible platelet units were identified to support her through the anticipated platelet nadir. Following conventional desensitization, cPRA did not change significantly. Following imlifidase-desensitization [0.25 mg/kg IV (D-1 and D1)], cPRA decreased significantly. 7 single-donor, antigen-avoidance platelet units produced corrected count increments (CCI) [median (interquartile range) of 6,000 (500-7500)]. The patient experienced no hemorrhage and was discharged stable, post-platelet engraftment on D+19. METHODS With IRB approval, patient data and samples (D-16; D-1 post-conventional desensitization with rituximab and therapeutic plasma exchange; D0 post-imlifidase dose 1; D2 post-imlifidase dose 2; and D7, D14 and D29 follow-up samples) were collected. Serial dilutions of patient D-1 serum were tested with SAB (LABScreen single antigen, One Lambda/ThermoFisher, West Hills, California). SDS-PAGE (gradient gel, non-reduced conditions), Western Blot (antiF(ab') detection), and SAB were performed and acceptable antigens (to molecular specificity, targeted by MFI ≤3,000) were compared over the clinical course. Summative MFIs targeting transfused single donor platelet units were compared with 1-hour CCI. Wilcoxon matched-pairs signed rank for matched, nonparametric values and Chi-squared or Fisher's exact for categorical variables were used. P &amp;lt;0.05 was significant. RESULTS/DISCUSSION The D-1 sample (post-conventional desensitization, pre-imlifidase) showed exquisite HLA sensitization. The highest Class A and B antibodies demonstrated an effective MFI of &amp;gt;4,000,000, each (Fig. A). PDAb and the number of unacceptable antigens decreased significantly in D0 (post-imlifidase) vs. D-1 (pre-imlifidase) samples; Intact IgG and scIgG were eliminated from the D0 and D2 samples (Fig. B). Of 7 single donor platelet transfusions, the 5 producing adequate response were each targeted by a summative MFI ≤4,000 (median 4,000 MFI, range 300-4,000). The 2 units producing inadequate CCI response were targeted by summative MFI &amp;gt;4,000 (5,050, 4,900-5,200), suggesting a threshold summative MFI precluding adequate response. CONCLUSIONS Here we show that the patient's pre-desensitization alloantibody levels significantly exceeded the analytical range of the SAB; PDAb levels declined significantly from baseline, correlating with lack of intact IgG and scIgG following imlifidase; and permissive transfusions (CCI &amp;gt;5,000) were seen to platelets targeted by ≤4,000 summative MFI. These results suggest imlifidase is capable of effective desensitization despite profound baseline sensitization, with rapid cleavage of intact IgG to F(ab'), resulting in the temporary reduction of unacceptable antigens. Larger scale investigation of imlifidase in desensitization of APR patients requiring significant transfusion over a limited period of time, along with investigation into transfusion strategies in desensitized APR, are warranted. REFERENCES Am J Transpl. 2022;22(3):691-697.Blood. 2022;140 (Suppl. 1):8562-3. .

EP12.03-03 A Case of Successful Desensitization Treatment with Tepotinib after Tepotinib-Induced Rash

EP12.03-03 A Case of Successful Desensitization Treatment with Tepotinib after Tepotinib-Induced Rash

Clinical characteristics of 15 cases of renal transplantation with pre-exsiting donor-specific antibody.

Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of postoperative complications and graft failure. The risk of postoperative complications and graft failure is relatively high. This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation, providing single-center treatment experience for DSA-positive kidney transplantation. We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022. Eight cases were organ donation after citizen's death (DCD) kidney transplant recipients, of which 3 cases in the early stage were not treated with preoperative desensitisation therapy (DCD untreated group, n=3), and 5 recipients were treated with preoperative rituximab desensitisation (DCD preprocessing group, n=5). The remaining 7 cases were living related donors recipients (LRD) who received preoperative desensitisation treatment with rituximab and plasma exchange (LRD preprocessing group, n=7). We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1, 3 and 5 years, and to compare the differences in recovery and postoperative complications between 3 groups. All 15 recipients were positive for preoperative panel reactive antibody (PRA) and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation. DCD untreated group all suffered from DSA level rebound, delayed renal graft function (DGF) and rejection reaction after surgery. After the combined treatment, DSA level was reduced and the graft renal function returned to normal. The DCD preprocessing group were all without antibody rebound, 1 recipient developed DGF and the renal function returned to normal after plasmapheresis, and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation. In the LRD preprocessing group, 2 cases had antibody rebound and 1 case had rejection, but all of them recovered to normal after treatment, and DSA was maintained at a low level or even disappeared. The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group; and there were no significant difference in the incidence of postoperative haematuria, proteinuria, bacterial and fungal infections, and BK virus infection between the 3 groups (all P>0.05). A total of 11 of the 15 recipients were followed up for more than 1 year, 6 for more than 3 years, and 1 for more than 5 years, and the survival rates of both the recipients and the transplanted kidneys were 100%. Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.