Rituximab In Lymphoma Patients Research Articles

Multifunctional DNA mediated spatially confined assembly for antibody orientation: Surpassing sensitivity and accuracy for rituximab detection

The sensitive, accurate and fast monitoring of therapeutic drugs plays an important role in guiding clinical medication or individualized treatment. Inspired by the highly efficient interactions of ordered structures in living organisms, a multifunctional DNA mediated spatially confined assembly (SCA) based antibody orientation strategy was proposed in this work. The multifunctional DNA containing a signaling molecule labeled on the head and a poly adenine tail (20 bases), can not only direct the ordered immobilization of antibodies on gold nanoparticles, but can also enrich electrochemical signal molecules. Compared with a randomly arranged antibody immobilization strategy, the SCA based antibody orientation strategy can produce nearly 200% of peak current signal. Moreover, MoS2/gold nanoparticles were used to modify electrodes in this study in order to improve the electrochemically active surface area and electron transfer of the electrode as well as the spatial regulation of thiol peptides. By using a highly specific CD20 epitope mimetic peptide this proposed biosensor exhibits high sensitivity for rituximab detection (LOD 56.4 fM) as well as good selectivity, stability and satisfactory accuracy. When applying it for detecting rituximab in lymphoma patients’ plasma, comparable results to commercial ELISA were obtained with a low RSD (＜6.5%). The proposed signal tag fabrication strategy could easily be extended to analyze other targets by changing the sensing platform, which has a potential application in the fields of biological analysis and medical diagnosis.

Anti-fouling poly adenine coating combined with highly specific CD20 epitope mimetic peptide for rituximab detection in clinical patients’ plasma

In this study, a high-performance anti-fouling coating based on poly adenine (polyAn) as well as a highly specific cluster of differentiation 20 (CD20) epitope mimetic peptide (CN14) were employed to synergistically construct a facile biosensor for the rapid and sensitive determination of rituximab in lymphoma patients' plasma. The well-designed and optimized polyAn coating displayed excellent stability, hydrophilicity, thanks to its intrinsic affinity with gold surface and thoroughly exposed hydrophilic phosphate groups. Moreover, the proposed strategy avoids the necessity to modify binding groups (e.g. thiol), making it more facile, repeatable and efficient. When dealing with complex clinical plasma samples, the polyAn coating demonstrated better anti-fouling performance and lower background signal in comparison with mercaptan and bovine serum albumin coatings. The dissociation constant (~60 nM) between CN14 and rituximab was measured by microscale thermophoresis and their binding mechanism was further explained using computer simulation. The constructed GE/CN14/polyA20 biosensor displayed satisfactory performance with detection limit of 35.26 ng/mL. Finally, the proposed biosensor was successfully applied for rapidly determining rituximab in lymphoma patients' plasma, and exhibited comparable accuracy to the commercial ELISA, but has advantages including a shorter detection time, wider detection range and lower cost. It's worth noting that the anti-fouling polyAn coating can be tailored according to the surface property of sensing interface and can be easily expanded to other gold electrode related biosensors.

A Tough Pill to Swallow: A Case of Rituximab-associated Esophageal Ulcers

Idiopathic giant esophageal ulcers were initially reported in patients with acquired immunodeficiency syndrome (AIDS), and later in other immunocompromised patients such as transplant recipients. However, there are no reported cases of esophageal ulcers associated with rituximab in lymphoma patients to our knowledge. A 44-year old male with history of Stage IV B-cell Lymphoma diagnosed 2 years ago, initially treated with Rituximab-Bendamustine, currently on rituximab maintenance therapy presented to the clinic for 2-week history of odynophagia and dysphagia. Physical exam was unremarkable. Labs showed WBC count of 2900 cells/uL with mild neutropenia of 1500 cells/uL and lymphopenia of 400 cells/uL (normal 0.7-4 k cells/uL). Esophagogastroduodenoscopy (EGD) showed multiple large ulcers in the mid-esophagus measuring 5-6 cm. Biopsies demonstrated reactive squamous epithelial changes and granulation tissue with no evidence of viral infection or malignancy. Testing for CMV, HSV, AFB, bacterial and fungal cultures, were negative. The patient was initially given a trial of PPI and empiric antiviral therapy with Valganciclovir for a week with no subjective improvement in symptoms. Repeat EGD showed mid-esophageal ulcers, unchanged from prior exam with negative biopsies. Repeat labs showed normal white count with Lymphopenia of 400 cells/uL. At this juncture, the patient was thought to have esophageal ulcers secondary to immunosuppression and rituximab was stopped. He was started on prednisone 20mg twice a day. He reported symptomatic relief within a week. EGD after 4 weeks showed healing ulcers. The patient is currently being tapered off the steroids. Idiopathic giant esophageal ulcers are rare and occur in the distal half of esophagus. Pathogenesis of these ulcers is unclear. Literature review shows few cases of idiopathic ulcers in AIDS and transplant patients that respond to steroid therapy with endoscopically documented healing. Alterations in the immune system leading to leukopenia may be the underlying mechanism for these ulcers. Even though our patient did not have a significant leukopenia, he did have lymphopenia. Rituximab may have induced an imbalance between various lymphocyte subpopulations and played a role in the pathogenesis of these ulcers. Steroid therapy and discontinuation of rituximab may have restored the immune balance. In conclusion, rituximab was the likely cause of multiple esophageal ulcers in our patient, and they responded to steroids.