Evusheld, a SARS-CoV-2 spike protein-directed attachment inhibitor, appears in serum protein electrophoresis and immunofixation: a case study.

Serum protein electrophoresis (SPE) and immunofixation (IFE) assays are commonly used to diagnose and monitor patients with multiple myeloma (MM). Identifying analytical interferences in SPE and IFE caused by therapeutic monoclonal antibodies (tmAbs) can be challenging. Here we report the case of a 72-year-old male with a long history of relapsed immunoglobulin (Ig)G kappa MM. A follow-up SPE showed the original peak plus 2 additional cathode peaks. Immunofixation was ordered as a reflex test to investigate the new peaks that showed initial patient monoclonal IgG kappa in addition to 2 restricted bands of the IgG kappa type. Therapeutic monoclonal antibody interference was suspected and the patient's chart was reviewed. The patient was not on any antimyeloma monoclonal antibody therapy. However, preexposure prophylaxis therapeutic monoclonal antibodies tixagevimab plus cilgavimab (Evusheld) for severe acute SARS-CoV-2 was administered approximately 45 minutes before sample collection, which led to the identifiable spikes and correlated bands. After 2 days, the IgG kappa bands disappeared, confirming this therapy's effect on SPE and IFE. Therefore, clinical pathologists should be aware of when providers prescribe new monoclonal antibody therapy and become familiar with the position of commonly prescribed (tmAbs) therapies at their institutions.

Long-Term Real-World Outcomes of Mepolizumab and Benralizumab Among Biologic-Naive Patients With Severe Eosinophilic Asthma: Experience of 3 Years' Therapy.

BACKGROUND: Biologic therapies such as mepolizumab and benralizumab offer treatment options for severe eosinophilic asthma (SEA), although long-term real-world data on their use are limited. OBJECTIVES: To evaluate the impact of benralizumab and mepolizumab treatment among biologic-naive patients with SEA over 36 months and describe the incidence of super-response at 12 and 36 months, identifying potential predictive factors. METHODS: We conducted a retrospective, single-center study of patients with SEA who were given mepolizumab or benralizumab from May 2017 to December 2019, and who completed 36 months of therapy. Baseline demographics, comorbidities, and medication use were described. Data on clinical outcomes, including maintenance oral corticosteroid (OCS) use, annual exacerbation rate (AER), mini Asthma Quality of Life Questionnaire, Asthma Control Questionnaire (ACQ-6), and eosinophil count were collected at baseline and at 12 and 36 months. Super-response was evaluated at 12 and 36 months. RESULTS: A total of 81 patients were included. Maintenance OCS use significantly improved from baseline (5.3 mg/d) to 12 months (2.4 mg/d, P < .0001) and 36 months (0.6 mg/d; P < .0001). Annual exacerbation rate decreased from baseline (5.8) to 12 months (0.9; P < .0001) and 36 months (1.2; P < .0001). Mini Asthma Quality of Life Questionnaire, ACQ-6, and eosinophil count significantly improved from baseline to 12 and 36 months. Twenty-nine patients demonstrated super-response at 12 months. Compared with those without a super-response, these patients had better baseline AER (4.7 vs 6.5; P = .009), mini Asthma Quality of Life Questionnaire (3.41 vs 2.54; P = .002), and ACQ-6 (3.38 vs 4.06; P = .03) scores. Most maintained a super-response up to 36 months. CONCLUSIONS: Mepolizumab and benralizumab are associated with significant improvements in OCS use, AER, and asthma control in real-world cohorts for up to 36 months, providing insight into long-term use for SEA.

SARS-COV-2 infections in inborn errors of immunity: A single center study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). One of the main topics of conversation in these past months in the world of immunology has been the issue of how patients with immune defects will fare if they contract this infection. To date there has been limited data on larger cohorts of patients with Inborn Errors of Immunity (IEI) diagnosed with COVID-19. Here, we review the data of COVID-19 infections in a single center cohort of 113 patients from the Mount Sinai Immunodeficiency program, who had 132 infections between January 2020 and June 2022. This included 56 males and 57 females, age range 2 - 84 (median 42). The mortality rate was 3%. Comparison between admitted patients revealed a significantly increased risk of hospitalization amongst the unvaccinated patients, 4% vaccinated vs 40% unvaccinated; odds ratio 15.0 (95% CI 4.2 - 53.4; p <0.00001). Additionally, COVID anti-spike antibody levels, determined in 36 of these patients post vaccination and before infection, were highly variable.

Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody.

As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of the previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryoelectron microscopy (cryo-EM) and X-ray crystallography. We show that mAb J08 has low nanomolar affinity against most VoCs and binds high on the receptor binding domain (RBD) ridge, away from many VoC mutations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.

Ex-vivo delivery of monoclonal antibody (Rituximab) to treat human donor lungs prior to transplantation.

BACKGROUND: Ex-vivo lung perfusion (EVLP) is an innovative platform for assessing donor lungs in the pre-transplant window. In this study, we demonstrate an extension of its utility by administering the anti-CD20 monoclonal antibody, Rituximab, during EVLP. We hypothesized that this would lead to targeted depletion of allograft B-cells which may provide significant clinical benefit, including the potential to reduce latent Epstein-Barr virus (EBV) and decrease the incidence of post-transplant lymphoproliferative malignancies. METHODS: Twenty human donor lungs rejected for transplantation were placed on EVLP with (n = 10) or without (n = 10) 500 mg of Rituximab. Safety parameters such as lung physiology and inflammatory cytokines were evaluated. We measured the delivery efficacy through flow cytometry, immunohistochemistry and ELISA. An in-vitro culture assay, in the presence of complement, was further conducted to monitor whether B-cell depletion would occur in Rituximab-perfused samples. FINDINGS: Rituximab was successfully delivered to human lungs during EVLP as evidenced by flow cytometric binding assays where lung tissue and lymph node biopsies demonstrated occupied CD20 epitopes after perfusion with the antibody. Lymph nodes from Rituximab perfusions demonstrated a 10.9 fold-reduction in CD20+ staining compared to controls (p = 0.0003). In lung tissue, Rituximab resulted in an 8.75 fold-reduction in CD20+ staining relative to controls (p = 0.0002). This decrease in CD20+ binding illustrates the successful delivery and occupation of epitopes after perfusion with the Rituximab. No apparent safety concerns were seen as exhibited by markers associated with acute cell injury (e.g., proinflammatory cytokines), cell death (e.g., TUNEL staining), or pulmonary physiology. In a post-perfusion tissue culture model, the addition of complement (human serum) resulted in evidence of B-cell depletion consistent with what would be expected with posttransplant activation of bound Rituximab. INTERPRETATION: Our experiments illustrate the potential of EVLP as a platform to deliver monoclonal antibody therapies to treat donor lungs pretransplant with the goal of eliminating a latent virus responsible for considerable morbidity after lung transplantation. FUNDING: Supported by the University Health Network Transplant Center.

Recognition and management of common, rare, and novel serum protein electrophoresis and immunofixation interferences.

Protein electrophoresis and immunofixation are subject to a variety of analytical interferences that may affect monoclonal protein diagnostics performed in the context of monoclonal gammopathies. Interferences include endogenous substances, such as hemoglobin and fibrinogen, and exogenous compounds, such as radiocontrast dyes, antibiotics, and monoclonal antibody therapies. General approaches to managing interferences begin with recognition of the problem. Provided herein are examples of common, rare, and novel interferences with the goal of providing a comprehensive overview. With each example, specific methods and strategies are provided to manage analytical interferences to ensure that interpretative reports are accurate. Longstanding and newer technologies are also described to contextualize where interferences may be identified and avoided.

Tratamento da doença de Crohn com infliximabe: primeira opção? / Treatment of Crohn's disease with infliximab: first choice?

RACIONAL: A doença de Crohn é uma inflamação crônica do trato gastrointestinal ainda de difícil tratamento. Há busca permanente de novos agentes que possam colaborar com a melhoria dos resultados. O infliximabe é um anticorpo monoclonal quimérico anti-fator de necrose tumoral alfa e está indicado na doença de Crohn refratária e fistulizante. OBJETIVO: Observar os resultados do tratamento da doença de Crohn com o anti-fator de necrose tumoral alfa. MÉTODOS: Estudo prospectivo de 60 doentes com doença de Crohn no período de seis anos. Foram considerados como critérios de exclusão: infecção atual ou nos últimos três meses; diagnóstico de tuberculose; quadro clínico e/ou radiológico de oclusão intestinal parcial ou total; gravidez ou amamentação. Todos os doentes foram previamente submetidos à radiografia do tórax, leucograma e intradermo reação para tuberculose. Foram tratados com infliximabe na dose de 5mg/kg de peso, aplicado por via endovenosa a intervalos de dois meses. Os doentes foram divididos em três grupos de acordo com o tempo de doença, isto é, grupo 1 aqueles com até cinco anos de diagnóstico, grupo 2 com seis até 10 anos e grupo 3 com mais de 10 anos de diagnóstico. Os resultados foram considerados subjetivamente através de protocolo após cada aplicação como: melhor, pior ou inalterado em relação ao estado geral do doente, sintomas intestinais e doença perianal. RESULTADOS: No tratamento inicial 76% dos pacientes responderam ao anticorpo. Observou-se que após a primeira dose da medicação, os com mais de 10 anos de doença e submetidos à operação abdominal tiveram resultado satisfatório semelhantemente aqueles doentes com menos de cinco anos de doença e não operados (62,5% e 80% respectivamente dos doentes que melhoraram), sendo este resultado estatisticamente significativo. CONCLUSÃO: O tratamento com infliximabe mostrou-se eficaz e tolerável no manejo dos sintomas dos pacientes com doença de Crohn ativa que não respondem ao tratamento convencional.

BACKGROUND: Crohn´s disease is a chronic inflammatory disorder of the gastrointestinal tract with difficult management. Infliximab is a chimeric IgG1 monoclonal antibody against tumor necrosis factor and is indicated for refractory luminal and fistulization in Crohn's disease. AIM: To observe the outcome of 60 patients with diagnosis of Crohn´s disease treated with infliximab. METHODS: Prospective study with 60 patients with Crohn´s disease in six years of observation. Exclusion criteria were: clinical infection in at last three months; tuberculosis; intestinal occlusion; pregnancy. All patients were submitted to thorax X-rays, leukogram, tuberculosis cutaneous test. They were treated with infliximabe 5mg/kg each two months. They were divided into three groups according to the time of the diagnosis: 5 years, 6 to 10 and more than 10 years. The results were considered better, worse or unchanged. RESULTS: After the initial treatment, 76% of the patients achieved a response. At the first dose, the ones with 10 years and with associated abdominal surgery had good results and similar to the ones with less than 5 years with no operations. CONCLUSION: The treatment with infliximab was effective and tolerable in the managing of symptoms in patients with active Crohn´s disease, refractory to the conventional treatment and can be a reasonable approach to avoid the surgical treatment.