Identification Of Antibodies Research Articles

Analysis of Rhesus (Rh) Antigen Distributions in Donors and Multi-transfused Patients for Phenotype-Matched Transfusion

Knowledge about the frequency of Rh blood group systems in the local population help build a donor pool for multi-transfused patients and provide antigen-negative compatible blood for patients with alloantibodies. ABO and Rh antigens were identified for blood donors and patients before transfusion. The antiglobulin test based on the micro-column gel method was used to perform unexpected antibody screening and identification for patients in pre-transfusion testing. The incidence of the adverse transfusion reactions and the accordance rate of Rh phenotype-matched transfusion were analyzed retrospectively. A total of 246,340 specimens were detected with Rh blood group antigens D, C, E, c, and e. Rh D antigen was the most common phenotype with a frequency of 99.40%, followed by e antigen, C antigen, c antigen, and E antigen. In Rh D positive specimens, DCe was the most common phenotype, while DCE was the least common. At the same time, in Rh D negative specimens, ce was the most common phenotype with CE and CcE unobserved. Rh phenotype-matched transfusion has been conducted in our department since 2012. The accordance rate of Rh phenotype-matched transfusion has been kept above 95% and the resulting incidence of adverse transfusion reactions has been decreasing year by year, from 19.95‰ in 2011 to 2.21‰ in 2021. Blood transfusion with matched Rh phenotypes was able to avoid the generation of unexpected antibodies, reduce the incidence of adverse transfusion reactions, and enhance precise diagnosis and treatment.

Linear epitope identification of monoclonal antibodies against the duck Tembusu virus NS1

Since 2010, the duck Tembusu virus (DTMUV) has caused a severe outbreak of egg drop syndrome in laying ducks in China, which has resulted in substantial financial losses in the poultry industry. DTMUV nonstructural protein 1 (NS1), as the only secreted protein, could aid in the development of therapeutic antibodies and diagnostic techniques; however, there are few studies on the preparation and epitope identification of monoclonal antibodies (mAbs) against DTMUV NS1. In this study, by indirect enzyme-linked immunosorbent assay (ELISA), Western blotting, and indirect immunofluorescence assay, we screened 6 mAbs (8A4, 8E6, 10F12, 1H11, 3D5, 5C11) that could specifically recognize DTMUV NS1. For epitope mapping of mAbs, a series of GST-tagged truncated fusion proteins of DTMUV NS1 were constructed by prokaryotic expression. Finally, the 4 shortest linear epitopes were identified by indirect ELISA and Western blotting. The epitope 133FVIDGPK139 was recognized by 8A4, the epitope 243IPKTLGGP250 was recognized by 8E6, the epitope 267PWDEK271 was recognized by 10F12, and 156EDFGFGVL163 was recognized by 1H11, 3D5, and 5C11. By sequence alignment and cross-reaction tests, we found that 8A4 and 8E6 had high specificity for DTMUV NS1 compared with that of other mAbs, but 10F12, 1H11, 3D5, and 5C11 exhibited a clear degree of cross-reaction with dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV) NS1. Finally, the predicted crystal structure analysis showed the approximate spatial positions of the 4 epitopes on the NS1 dimer. In summary, our study revealed 2 specific mAbs for DTMUV NS1 recognition and 4 multiflavivirus mAbs for DENV, JEV, WNV, and ZIKV NS1 recognition.

The Incidence of Evanescent Antibodies to Red Blood Cell Antigens in a Tertiary Care Hospital in Northern India

Background and Objectives: The anti-A and anti-B are naturally occurring antibodies in the human body but alloantibodies may be formed in individuals who lacks that corresponding red cell antigen after any sensitising event like blood transfusion or pregnancy. The aim of this study was to find the incidence of evanescenct RBC alloantibodies that may not be detectable at the time of pre-transfusion screening. Methods: This was a retrospective observational study from January 2017 to May 2019 in a tertiary care centre from North India. The data on antibody screening and identification retrieved from the departmental records. The patients were screened for red blood cell antibody and those with a positive screening test were further investigated for antibody identification. Antibody screening was performed by solid phase method using Immucor Capture-R Ready Screen (4 cell). Confirmed positive samples were investigated with advance methods of Antibody ID using Reagent panel Red Blood Cells Capture-R Ready ID (16 Cell) in Automated Analyzer Iris or Neo (Immucor Inc. Nocross, GA, USA). As and when required other advance techniques of adsorption and elution, etc were also performed too. Results: The total number of patient screened during this period were 8071. Amongst them 312 were positive for antibody screening (3.8%), of those 216 (62.9%) cases had alloantibodies and 96 (30.7%) cases had autoantibodies. Among the 216 cases of alloantibody, 147 (68.1%) cases had single alloantibody and 69 (31.9%) cases had multiple alloantibodies. Amongst the patients having single alloantibody, the prevalence was highest for Anti-D 54 (36.7%), followed by Anti-E 27 (18.3%), Anti-C 8 (5.4%), Anti-c 7 (4.7%), Anti-K 9 (6.1%), Anti-Fyb 11 (7.4%), Anti-M 18 (12.2%), Anti-N 4 (2.7%), Anti-Fyb 3 (2%), Anti-Lea 3 (2%), Anti-Cw 2 (1.3%) and Anti-Mia 1 (0.6%). Of the 96 patients with autoantibody 72 had warm autoantibody, 10 had cold autoantibody and there were 8 cases of mixed warm and cold autoantibodies. There were 6 patients with warm autoantibody with underlying alloantibody. Conclusion: In conclusion, the high prevalence of Anti-Rh (Anti-D, E), Anti-M, Anti-Fyb antibodies in patient requiring transfusion reiterates the importance of stringent antibody screening and identification as an essential step in preventing delayed hemolytic transfusion reaction.

Clinico-Epidemiological Laboratory Findings of COVID- 19 Positive Patients in a Hospital in Saudi Arabia.

Understanding COVID-19's onset and clinical effects requires knowing host immune responses. To investigate the presence of IgM, IgG, and cytokine levels (IL-2 and IL-6) in individuals with COVID-19 who have had their diagnosis confirmed by PCR. This cross-sectional research included 70 adult ICU patients from King Abdullah Hospital in Bisha, Saudi Arabia. Subjects gave two blood samples. After hospital release, only 21 patients provided the second sample. Each patient provided a sample upon admission. Quantitative ELISAs evaluated IL-2, IL-6, and SARS-CoV-2-specific IgM and IgG antibodies. All patients were critically ill and unvaccinated against COVID-19. 46 (65.7%) of the patients were male, and their age range was 33-98 years (with a mean age of 66.5); 24.3%) were 51-61 years old. IgG was positive in all patients, although IgM predominated in 57/70 (81.4%) (6-1200 IU/mL). Total data analysis yielded these results. IL-6 was calculated at 10-1900 ng/mL, whereas IL-2 was 4-280. Discharged hospital patients had a statistically significant increase in IgM and IgG (P = 0.01, 0.004) but a statistically insignificant decline in IL-6 and IL-2 (P = 0.761, 0.071). Low IgM levels increased hospital stays. The study found lengthier hospital stays with higher IgG levels. The identification of IgM and IgG antibodies, greater IL-6 levels, and lower IL-2 levels can help diagnose and monitor COVID-19 infection.

Autoimmune nodo-paranodopathies 10 years later: Clinical features, pathophysiology and treatment.

Autoimmune neuropathies are classified, on the basis of pathophysiology, as demyelinating or axonal. The term nodo-paranodopathy, introduced in 2013 to better categorize the neuropathies with antiganglioside antibodies and later expanded to include neuropathies with antibodies to nodal and paranodal axoglial complexes, characterizes disorders in which the nodal region is critical in the pathogenesis. These neuropathies, although presenting electrophysiologic demyelinating features do not show pathologic evidence of segmental demyelination, or, although being classified as axonal, can show reversible nerve conduction failure and rapid recovery contrary with the communal concept of an axonal neuropathy. In this personal view is reported, with a splitting approach, an update on autoimmune nodo-paranodopathies, classified according to the domains of peripheral nerve fiber, the target antigens and the antibody class and subclass involved. The clinical features, the electrophysiologic findings, the results of the immunopathological and ultrastructural studies, the pathophysiology and treatment are also described. The nodo-paranodopathy category integrates the clinical classification of autoimmune neuropathies and expands the traditional dichotomous demyelinating and axonal classification. It helps to a better systematization pointing to the domain and target antigens of the autoimmune process, it resolves conflicting pathologic and electrophysiologic findings, reconciles the contradiction that axonal neuropathies may be rapidly reversible, avoids taxonomical confusion and possible misdiagnoses. Finally this categorization, through the identification of the specific antibody and its prevalent class and subclass, clarifies the pathophysiological mechanisms and addresses to a more targeted therapeutic approach.

Liposomes: from August Wassermann to vaccines against COVID-19.

The development of vaccines against the SARS-CoV-2 virus has become a big challenge for many countries in 2020-2022. mRNA vaccines were shown to be effective and safe and have been widely used worldwide in the fight against the COVID-19 pandemic. The fundamental factor in creating mRNA vaccines, which ensures effective delivery of mRNA to the host cells, is the composition of lipid nanoparticles, namely the presence of ionized charged lipids, which ensures the binding of mRNA molecules. However, the significant role of liposomes in the development of liposomal vaccines and identification of immunochemical reactions involving lipids should be assessed in the context of the development of the pioneering idea of August Wassermann about the use of liposomal antigens in the diagnosis and immunoprophylaxis of serious human diseases. The review is devoted to the use of liposomal antigens as antigen-delivery systems for diagnosis and immunoprophylaxis. Studies of cardiolipin antigen in serodiagnosis of syphilis became the foundation of antibodies in diagnosing various infectious diseases and pathological conditions, such as tuberculosis, lupus erythematosus, COVID-19, borreliosis, etc. Identification of antiphospholipid antibodies (mainly anticardiolipin) and today is the most important diagnostic tool for antiphospholipid syndrome. The liposomal system first proposed in 1906 for the diagnosis of syphilis evolved more than a century later into mRNA vaccines, which are used today in the fight against the COVID-19 pandemic.

The identification of high-performing antibodies for RNA-binding protein TIA1 for use in Western Blot, immunoprecipitation and immunofluorescence

A member of the RNA-binding protein family, T-cell intracellular antigen-1 (TIA1) regulates mRNA translation and splicing as well as cellular stress by promoting stress granule formation. Variants of the TIA1 gene have implications in neurogenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Reproducible research on TIA1 would be enhanced with the availability of high-quality anti-TIA1 antibodies. In this study, we characterized twelve TIA1 commercial antibodies for Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.

The identification of high-performing antibodies for RNA-binding protein FUS for use in Western Blot, immunoprecipitation, and immunofluorescence.

RNA-binding protein Fused-in Sarcoma (FUS) plays an essential role in various cellular processes. Mutations in the C-terminal domain region, where the nuclear localization signal (NLS) is located, causes the redistribution of FUS from the nucleus to the cytoplasm. In neurons, neurotoxic aggregates are formed as a result, contributing to neurogenerative diseases. Well-characterized anti-FUS antibodies would enable the reproducibility of FUS research, thereby benefiting the scientific community. In this study, we characterized ten FUS commercial antibodies for Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.

The identification of high-performing antibodies for TDP-43 for use in Western Blot, immunoprecipitation and immunofluorescence.

TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein playing a critical role in the regulation of transcription, splicing and RNA stability. Mutations in TARDBP leading to aggregation, are suspected to be a characteristic feature of various neurogenerative diseases. The lack of well-characterized anti- TDP-43 antibodies acts as a barrier to establish reproducible TDP-43 research. In this study, we characterized eighteen TDP-43 commercial antibodies for Western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many well-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.

Neonatal hemolytic disease: How should we use indirect and direct antiglobulin tests?

In newborns with hemolysis, the direct antiglobulin test (DAT) and indirect antiglobulin test (IAT) play a key role in demonstrating the presence of an immune cause. We aimed to emphasize the importance of IAT in mothers of DAT-positive babies. DAT was performed with forward blood grouping on cord blood in term babies who were born between September 2020 and September 2022. IAT was performed in the mothers of the babies who were found to have a positive DAT and antibody identification was performed in the mothers who were found to have a positive IAT. Specific antibodies detected and identified were associated with the clinical course. The study included 2769 babies and their mothers. The prevalence of DAT positivity was found to be 3.3% (87 of 2661). In DAT-positive babies, the rate of ABO incompatibility was 45.9%, the rate of RhD incompatibility was 5.7% and the rate of RhD and ABO incompatibility in association was 10.3%. The rate of subgroup incompatibility and other red blood cell antibodies was 18.3%. Phototherapy was applied because of indirect hyperbilirubinemia in 16.6% of the DAT-negative babies and in 51.5% of the DAT-positive babies. The need for phototherapy was significantly higher in DAT-positive infants (p<0.01). Severe hemolytic disease of the newborn, bilirubin level, duration of phototherapy and use of intravenous immunoglobulin were found to be significantly higher in the babies whose mothers were IAT positive compared with the babies whose mothers were IAT negative (p<0.01). IAT should be performed on all pregnant women. When screening with IAT is not performed during pregnancy, performing DAT in the baby plays a key role. We showed that the clinical course was more severe when mothers of DAT-positive babies were IAT positive.

Epstein-Barr Virus-induced Paroxysmal Cold Hemoglobinuria in a 17-Year-old Male.

Paroxysmal cold hemoglobinuria is a rare autoimmune hemolytic anemia seen almost exclusively in children under 5 years of age after a viral illness. It is mediated by a biphasic polyclonal autoantibody against red blood cells, which causes severe hemolysis that typically self-resolves within 2 weeks without recurrence. While laboratory identification of the aforementioned antibody, the Donath Landsteiner antibody, would confirm this diagnosis, a negative test does not rule out this condition in the appropriate clinical context. We report on the rare occurrence of a severe presentation of paroxysmal cold hemoglobinuria in a 17-year-old male with Epstein-Barr virus infection.

NAV-001, a high-efficacy antibody-drug conjugate targeting mesothelin with improved delivery of a potent payload by counteracting MUC16/CA125 inhibitory effects.

Subsets of tumor-produced cell surface and secreted proteins can bind to IgG1 type antibodies and suppress their immune-effector activities. As they affect antibody and complement-mediated immunity, we call these proteins humoral immuno-oncology (HIO) factors. Antibody-drug conjugates (ADCs) use antibody targeting to bind cell surface antigens, internalize into the cell, then kill target cells upon liberation of the cytotoxic payload. Binding of the ADC antibody component by a HIO factor may potentially hamper ADC efficacy due to reduced internalization. To determine the potential effects of HIO factor ADC suppression, we evaluated the efficacy of a HIO-refractory, mesothelin-directed ADC (NAV-001) and a HIO-bound, mesothelin-directed ADC (SS1). The HIO factor MUC16/CA125 binding to SS1 ADC was shown to have a negative effect on internalization and tumor cell killing. The MUC16/CA125 refractory NAV-001 ADC was shown to have robust killing of MUC16/CA125 expressing and non-expressing tumor cells in vitro and in vivo at single, sub-mg/kg dosing. Moreover, NAV-001-PNU, which contains the PNU-159682 topoisomerase II inhibitor, demonstrated good stability in vitro and in vivo as well as robust bystander activity of resident cells while maintaining a tolerable safety profile in vivo. Single-dose NAV-001-PNU demonstrated robust tumor regression of a number of patient-derived xenografts from different tumor types regardless of MUC16/CA125 expression. These findings suggest that identification of HIO-refractory antibodies to be used in ADC format may improve therapeutic efficacy as observed by NAV-001 and warrants NAV-001-PNU's advancement to human clinical trials as a monotherapy to treat mesothelin-positive cancers.

Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants.

We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.

Treponemal Antibody Seroprevalence Using a Multiplex Bead Assay from Samples Collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey: Searching for Yaws in Nigeria.

Yaws is a chronic, relapsing disease of skin, bone, and cartilage caused by Treponema pallidum subsp. pertenue. Yaws was last reported in Nigeria in 1996, although neighboring countries have recently reported cases. We investigated serological evidence for yaws among children aged 0-14 years in Nigeria by measuring antibodies to the treponemal antigens rp17 and TmpA in blood specimens from a 2018 nationally representative HIV survey using a multiplex bead assay. The presence of antibodies to both antigens ("double positive") likely reflects current or recent treponemal infection. Overall, 1.9% (610/31,549) of children had anti-TmpA antibodies, 1.5% (476/31,549) had anti-rp17 antibodies, and 0.1% (39/31,549) were double positive. Among households, 0.5% (84/18,021) had a double-positive child, with a clustering of double-positive children. Although numbers are low, identification of antibodies to both TmpA and rp17 may warrant investigation, including more granular epidemiologic and clinical data, to assess the potential for continuing yaws transmission in Nigerian children.

Determination of autoantibody repertoire in the mouse model of viral myocarditis and in patients with non-ischemic cardiomyopathy by PhIP-Seq

Abstract Various infectious and non-infectious agents can cause myocarditis that may lead to cardiomyopathy with viruses being the most common suspects. Mechanistically, autoantibodies have been demonstrated for various antigens, in animal models and dilated cardiomyopathy patients, but their role continues to be enigmatic. First, by using the Coxsackievirus B3 (CVB3) infection model in A/J mice, we applied PhIP-Seq, a high-throughput platform to evaluate antibodies for various antigens. The data revealed the identification of antibodies to 32 antigens that were not previously reported. By investigating the biological significance of a few select antigens, we noted that cytochrome c oxidase assembly factor 4 homolog (COA4)-reactive antibodies were generated only in mice infected with CVB3 but not in influenza-infected animals proving virus specificity for antibody reactivity to COA4. Further immunogenicity studies revealed that animals immunized with COA4 did not develop myocarditis, nor was the T cell response generated, implying that COA4 is unlikely to act as a bonafide autoantigen. Alternatively, the COA4-reactive antibodies may represent biomarkers of viral myocarditis. Second, using the PhIP-Seq platform, we investigated the antibody profiles of human sera obtained from 25 age-matched non-ischemic cardiomyopathy patients and healthy controls. The analysis revealed significantly elevated levels of antibodies to 33 antigens, and the detection of the major candidates is being analyzed by ELISA as a secondary assay. Overall, our data suggest that the PhIP-Seq allows us to comprehensively analyze antibody repertoires that may lead to the identification of novel autoantibodies or their use as biomarkers. This work was supported in part by the institutional funds from the University of Nebraska-Lincoln (J.R.), the Transformational Grant 18TPA34170206 from the American Heart Association (J.R.), and the National Institutes of Health grants R01 HL114669 (J.R), R01 GM136724 (H.B.L.).

Sequence enrichment profiles enable target-agnostic antibody generation for a broad range of antigens

Phenotypic drug discovery (PDD) enables the target-agnostic generation of therapeutic drugs with novel mechanisms of action. However, realizing its full potential for biologics discovery requires new technologies to produce antibodies to all, a priori unknown, disease-associated biomolecules. We present a methodology that helps achieve this by integrating computational modeling, differential antibody display selection, and massive parallel sequencing. The method uses the law of mass action-based computational modeling to optimize antibody display selection and, by matching computationally modeled and experimentally selected sequence enrichment profiles, predict which antibody sequences encode specificity for disease-associated biomolecules. Applied to a phage display antibody library and cell-based antibody selection, ∼105 antibody sequences encoding specificity for tumor cell surface receptors expressed at 103-106 receptors/cell were discovered. We anticipate that this approach will be broadly applicable to molecular libraries coupling genotype to phenotype and to the screening of complex antigen populations for identification of antibodies to unknown disease-associated targets.

Situation analysis and blood transfusion strategy of Lewis antibodies in Hunan Province.

Detection rate, serological characteristics, and clinical data of patients with Lewis blood group antibodies in Hunan Province were analyzed through retrospective analysis. This was undertaken in order to optimize the detection methods and blood transfusion strategies of these patients. Blood typing, antibody screening, and cross-matching were performed by microcolumn gel, and Lewis antigen was detected by immediate spin test, antibody identification of positive and negative ABO samples, positive antibody screening, and cross-blood mismatch samples. Antibodies were identified by immediate spin test and microcolumn gel antiglobulin method, and the clinical data of the patients with Lewis antibody characteristics were analyzed. A total of 74 samples (15.91%) with Lewis antibodies were detected from 465 positive samples; cases were distributed in different cities of Hunan Province, with Changsha city being the most frequent (28%) one, with mostly non-O (66), anti-Lea (31; 41.89%), anti-Lea+anti-Leb (23; 31.08%), anti-Leb (5; 6.76%), anti-LebH and anti-Lea+anti-LebH (1+4; 6.76%), and antibody types immunoglobulin M (IgM) (51; 68.92%), immunoglobulin G (8; 10.81%), and IgG+IgM (4; 5.41%) cases. Patients included more females (67.57%) than males. The detection rate of gynecological diseases and patients with solid tumors was highest (44.59%). In all cases, the Lewis blood group was Le (a-b-); none of the 15 transfusion patients had hemolytic transfusion reaction. A variety of experimental methods must be adopted simultaneously to determine specificity and prevent the leakage of Lewis antibodies. The infusion of red blood cells matching with antiglobulin media at 37°C was recommended to ensure safe transfusion for recipients with Lewis antibodies.

The identification of high-performing antibodies for Vacuolar protein sorting-associated protein 35 (hVPS35) for use in Western Blot, immunoprecipitation and immunofluorescence

Vacuolar protein sorting-associated protein 35 is a subunit of the retromer complex, a vital constituent of the endosomal protein sorting pathway. The D620N mutation in theVPS35gene has been reported to be linked to type 17 Parkinson’s Disease progression, the exact molecular mechanism remains to be solved. The scientific community would benefit from the accessibility of validated and high-quality anti-hVPS35 antibodies. In this study, we characterized thirteen hVPS35 commercial antibodies for Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.

Temporal Relationship of Breast Cancer and Paraneoplastic Neuromyelitis Optica Spectrum Disorder (NMOSD) (P13-5.001)

<h3>Objective:</h3> A systematic review and meta-analysis was conducted in order to characterize the temporal relationship between the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) and breast cancer. <h3>Background:</h3> Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory and demyelinating disorder affecting the optic nerve and spinal cord more frequently than other parts of the central nervous system (CNS). NMOSD was recognized as a unique condition with a chronic, relapsing course after the identification of IgG-class antibodies that bind to the water channel aquaporin-4 (AQP4-IgG) in serum from individuals with NMO. Typically this is an idiopathic autoimmune disorder, although there is increasing evidence behind the expression of AQP4 antibodies in the setting of an underlying tumor with NMOSD manifesting as a paraneoplastic syndrome. <h3>Design/Methods:</h3> This systematic review and meta-analysis was completed in accordance PRISMA guidelines. A literature search was conducted on PubMed/PubMed Central/MEDLINE, Scopus, and ScienceDirect databases. The review was registered with PROSPERO (Registration ID: CRD42022352109). <h3>Results:</h3> The search strategy yielded a total of 10 records, from which 16 cases were identified. Triple-negative breast cancer was the most prevalent form of breast cancer. Seven cases recorded the presence of longitudinally extensive transverse myelitis (LETM) involving the cervical and thoracic cord. Five cases identified lesions on magnetic resonance imaging (MRI) within the brainstem. And four cases described lesions within the cerebrum and/or cerebellum. Intravenous methylprednisolone (IVMP) was the most common agent used in the acute management of NMOSD. On average the diagnosis of NMOSD occurred 1.4 months before that of breast cancer. <h3>Conclusions:</h3> NMOSD is a rare autoimmune condition that can occur in a paraneoplastic manner. The diagnosis of NMOSD precedes that of breast cancer with a mean time of 1.4 months. Triple-negative breast cancer is the most commonly identified subtype. Common MRI findings include LETM of the cervical and thoracic cord as well as brainstem lesions. <b>Disclosure:</b> Dr. Sivakumar has nothing to disclose. Dr. Srichawla has nothing to disclose. Dr. Cheraghi has nothing to disclose.

Pre-transfusion Testing Using Crossmatching Agglutination Reaction Grades Combined With Rh Subgroup Phenotyping in Patients With Autoantibodies: A Three-year Experience at a Tertiary Hospital.

The currently recommended pre-transfusion testing techniques for patients with autoantibodies are complex, time-consuming, and labor-intensive. Therefore, although the red blood cell (RBC) selection method using crossmatched RBC agglutination reaction grades (i.e., the "least incompatible" transfusion) is discouraged, many institutions still use it. We aimed to evaluate the effectiveness of this method combined with Rh subgroup phenotyping. We retrospectively investigated RBC transfusions from January 2019 to December 2021 in patients presenting as auto-control-positive via antibody identification (auto-control (+) group), where Rh subgroup phenotype-matched RBCs were selected based on the agglutination reaction grades of crossmatched units. For each study patient, an auto-control-negative patient was matched based on age, sex, department, and pre-transfusion Hb levels (auto-control (-) group). The mean Hb change per unit, transfusion-associated symptom/sign reports, and agglutination reaction grades upon crossmatching were analyzed. In the auto-control (+) group, the Hb change per unit among different agglutination reaction grades of transfused RBCs and among different relative grades of transfused RBCs and crossmatching auto-controls was not significantly different (P=0.392 and P= 0.132, respectively). No significant difference was observed in Hb changes and transfusion-associated symptom/sign occurrence between the auto-control (+) and auto-control (-) groups (P=0.121 and P=0.822, respectively). In addition, no definite evidence of hemolysis in the auto-control (+) group was observed in the medical record review. Together with Rh subgroup phenotyping, selecting the RBC unit with the lowest agglutination reaction grade upon crossmatching does not adversely affect transfusion efficiency.