B Cell Differentiation and the Origin and Pathogenesis of Human B Cell Lymphomas.

Immunoglobulin (IG) gene remodeling by V(D)J recombination plays a central role in the generation of normal B cells, and somatic hypermutation and class switching of IG genes are key processes during antigen-driven B cell differentiation in the germinal center reaction. However, errors of these processes are involved in the development of B cell lymphomas. IG locus-associated translocations of proto-oncogenes are a hallmark of many B cell malignancies. Additional transforming events include inactivating mutations in various tumor suppressor genes and also latent infection of B cells with viruses, such as Epstein-Barr virus. Most B cell lymphomas require B cell antigen receptor expression, and in several instances chronic antigenic stimulation plays a role in lymphoma development and/or sustaining tumor growth. Often, survival and proliferation signals provided by other cells in the microenvironment are a further critical factor in lymphoma development and pathophysiology. Most B cell malignancies derive from germinal center B cells, most likely due to the high proliferative activity of these B cells and aberrant mutations caused by their naturally active mutagenic processes.

Expression Cloning of Antibodies from Single Human B Cells.

The majority of lymphomas originate from B cells at the germinal center stage. Preferential selection of B-cell clones by a limited set of antigens has been suggested to drive lymphoma development. While recent studies in B-cell chronic lymphocytic leukemia (CLL) have shown that self-reactive B-cell receptors (BCR) can generate cell-autonomous signaling and proliferation, our knowledge about the role of BCRs for the development or survival of other lymphomas remains limited. Here, we describe a strategy to characterize the antibody reactivity of human B cells. The approach allows for unbiased characterization of the human antibody repertoire on single-cell level through the generation of recombinant monoclonal antibodies from primary human B cells of defined origin. This protocol offers a detailed description of the method starting from the flow cytometric isolation of single human B cells to the RT-PCR-based amplification of the expressed immunoglobulin (Ig) transcripts (IGH, IGK, and IGL) and their subsequent cloning into expression vectors for the in vitro production of recombinant monoclonal antibodies. The strategy may be used to obtain information about the clonal evolution of B-cell lymphomas by single-cell sequencing of Ig transcripts and on the antibody reactivity of human lymphoma B cells.

Stereotyped B-Cell Receptor Immunoglobulins in B-Cell Lymphomas.

Thorough examination of clonotypic B-cell receptor immunoglobulin (BcR IG) gene rearrangement sequences in patients with mature B-cell malignancies has revealed significant repertoire restrictions, leading to the identification of subsets of patients expressing highly similar, stereotyped BcR IG. This discovery strongly suggests selection by common epitopes or classes of structurally similar epitopes in the development of these tumors. Initially observed in chronic lymphocytic leukemia (CLL), where the stereotyped fraction accounts for a substantial fraction of patients, stereotyped BcR IGs have also been identified in other mature B-cell malignancies, including mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL).Further comparisons across different entities have indicated that stereotyped IGs are predominantly "disease-biased," indicating distinct immune pathogenetic trajectories. Notably, accumulating evidence suggests that molecular subclassification of mature B-cell malignancies based on BcR IG stereotypy holds biological and clinical relevance. Particularly in CLL, patients belonging to the same subset due to the expression of a specific stereotyped BcR IG exhibit consistent biological backgrounds and clinical courses, especially for major and extensively studied subsets. Therefore, robust assignment to stereotyped subsets may aid in uncovering mechanisms underlying disease initiation and progression, as well as refining patient risk stratification. In this chapter, we offer an overview of recent studies on BcR IG stereotypy in mature B-cell malignancies and delineate past and present methodological approaches utilized for the identification of stereotyped BcR IG.

MRD Detection in B-Cell Non-Hodgkin Lymphomas Using Ig Gene Rearrangements and Chromosomal Translocations as Targets for Real-Time Quantitative PCR and ddPCR.

Minimal residual disease (MRD) diagnostics is of high clinical relevance in patients with indolent B-cell non-Hodgkin lymphomas (B-NHL), B-cell chronic lymphocytic leukemia (CLL), and multiple myeloma and serves as a surrogate parameter to evaluate treatment effectiveness and long-term prognosis. Real-time quantitative PCR (RQ-PCR) targeting circulating lymphoma cells is still the gold standard for MRD detection in indolent B-NHL and currently the most sensitive and the most broadly applied method in follicular lymphoma (FL) and mantle cell lymphoma (MCL). Alternatively, droplet digital PCR (ddPCR) can be used for MRD monitoring in multiple myeloma, mantle cell lymphoma, CLL, and FL with comparable sensitivity, accuracy, and reproducibility.The most broadly applicable MRD target in B-NHL is the junctional regions of the rearranged immunoglobulin heavy (IGH) and light chain genes. Complete and incomplete IGH and additionally IG kappa light chain rearrangements can be used as targets for MRD. Next-generation sequencing (NGS) of IG-rearrangements (IG-NGS) as new sequencing-based technology can overcome the limitation of PCR-based approaches and has a potential for higher sensitivity. Chromosomal translocations like the t(14;18)(q32;q21) translocation associated with IGH::BCL2 fusion in FL and t(11;14)(q13;q32) translocation in MCL leading to the IGH::CCND1 fusion can be used as MRD target in selected lymphoma subtypes. In patients with CLL, both flow-cytometry and RQ-PCR are equally suited for MRD assessment as long as a sensitivity of 10-4 is achieved.MRD diagnostics targeting the IG loci is complex and requires extensive knowledge and experience because the junctional regions of each clonal rearranged gene have to be identified before the patient-specific PCR assays can be designed for MRD monitoring. In addition, the presence and load of somatic hypermutation within the rearranged IGH gene occurring during B-cell development of germinal center and post-germinal center B-cell lymphomas may hamper appropriate primer binding leading to false-negative results. The translocations mentioned above have the advantage that consensus forward primers and probes, both placed in the breakpoint regions of chromosome 18 in FL and chromosome 11 in MCL, can be used in combination with a reverse primer placed in the IGH joining region of chromosome 14. PCR-based methods using allele-specific primers can reach a high sensitivity of up to 10-5. This chapter provides all relevant background information and technical aspects for the complete laboratory process from detection of the clonal IG gene rearrangements and the chromosomal translocations at diagnosis to the actual MRD measurements in clinical follow-up samples of B-NHL. However, it should be noted that MRD diagnostics for clinical treatment protocols has to be accompanied by regular international quality control rounds to ensure the reproducibility and reliability of the MRD results. This is available by the EuroMRD network ( https://euromrd.org ), a subgroup of ESHLO ( https://eslho.org ).

PCR GeneScan Analysis of Rearranged Immunoglobulin or T-Cell Receptor Genes for Clonality Diagnostics in Suspect Lymphoproliferations.

Assessment of the presence of clonal lymphoproliferations via polymerase chain reaction (PCR)-based analysis of rearranged immunoglobulin (IG) or T-cell receptor (TR) genes is a valuable method in the diagnosis of suspect lymphoproliferative disorders. Additionally, this methodology can be used for evaluating dissemination of lymphoma cells and for studying the clonal relationship between multiple (different locations) and consecutive (over time) lymphomas. Here we describe an integrated approach to assess clonality via analysis of Ig heavy chain (IGH), Ig kappa (IGK), TCR beta (TRB), and TCR gamma (TRG) gene rearrangements, based on the standardized multiplex PCRs as originally developed by the European BIOMED-2 consortium (currently named EuroClonality). The described protocol covers the pre-analytical phase of DNA isolation (from formalin-fixed paraffin-embedded and fresh tissues, body fluids, peripheral blood, and bone marrow), the analytical phase of PCR GeneScan analysis, and the post-analytical interpretation of the obtained profiles, following established guidelines.

Associations of multiple metals exposure with immunoglobulin levels in pregnant women: Hangzhou Birth Cohort Study.

Metal may affect maternal immune function, but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin (Ig) levels. Based on the Hangzhou Birth Cohort Study, 1059 participants were included, and eleven metals in whole blood samples and serum IgA, IgG, IgE and IgM levels were measured. Linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) models were used to evaluate the associations. Compared with the first tertile of metal levels, arsenic (As) was negatively associated with IgE (ß = -0.25, 95% confidence interval (CI) = -0.48 to -0.02). Moreover, significant associations of manganese (Mn) with IgA, IgG and IgM were demonstrated (ß = 0.10, 95% CI = 0.04 to 0.18; ß = 0.07, 95% CI = 0.03 to 0.12; ß = 0.10, 95% CI = 0.03 to 0.18, respectively). Cadmium (Cd) were associated with higher levels of IgM. QGC models showed the positive association of the metal mixtures with IgA and IgG, with Mn playing a major role. Mn and Cd had positive contributions to IgM, while As had negative contributions to IgE. In the BKMR models, the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th percentile. Therefore, exposure to metals was associated with maternal Igs, and mainly showed that Mn was associated with increased levels of IgA, IgG and IgM, and As was associated with low IgE levels.

Immunoglobulin G4 -related gastrointestinal disease associated with type 1 autoimmune pancreatitis: A case report.

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

Key differences between chronic inducible and spontaneous urticaria.

Introduction: The latest international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for urticaria recommends limited laboratory testing for chronic spontaneous urticaria (CSU) and selective testing for only certain chronic inducible urticaria (CIndU) subtypes, though the rationale for these recommendations is poorly explained. This study aimed to improve the understanding of CIndU subtypes by comprehensively comparing their demographic, clinical, and laboratory characteristics with those of the better-characterized CSU. Methods: We conducted a retrospective analysis of 567 patients (median age 41 years, 67% female) diagnosed with CSU, symptomatic dermographism (SD), cold urticaria (ColdU), cholinergic urticaria (CholU), and delayed pressure urticaria (DPU). Results: Our findings revealed that patients with SD, ColdU, and CholU had lower levels of C-reactive protein (CRP), higher total serum immunoglobulin E (IgE) levels, and higher basophil counts compared to CSU patients. These subtypes also had distinct demographic and clinical features, such as a younger age of onset and a longer disease duration. In contrast, patients with DPU had significantly higher CRP levels and neutrophil counts compared to those with CSU. Discussion: These findings highlight the heterogeneity among chronic urticaria subtypes, suggesting that a tailored approach to laboratory testing may be more effective. The distinct immunological and clinical features observed in CIndU subtypes suggest a need for subtype-specific diagnostic and therapeutic guidelines.

Serial Imaging Follow-Up for Immunoglobulin G4-Related Coronary Arteritis With Acute Coronary Syndrome.

A 49-year-old Japanese man received a diagnosis of immunoglobulin G4-related coronary arteritis (IgG4-RCA), discovered following the detection of abdominal aorta wall thickening on computed tomography (CT). Intravascular ultrasonography (IVUS) revealed thickening of both the adventitia and the intima-media complex (IMC) in the left anterior descending (LAD) coronary artery, without significant stenosis. Corticosterone therapy was administered. On the fifth day of corticosterone therapy, the patient experienced an acute coronary syndrome secondary to LAD artery ostium occlusion, and a primary percutaneous coronary intervention was performed. After 3 months of corticosterone therapy, IVUS follow-up showed a decrease in the adventitia and IMC thickening. After 9 months of corticosterone therapy, positron emission tomography combined with CT revealed that the abnormal accumulation of fluorodeoxyglucose in the coronary arteries and abdominal aorta had disappeared. Considering the treatment process and the existing literature, there is a possibility that the adventitia and IMC deformation was induced by IgG4-RCA.

Establishment and Validation of Fecal Secretory Immunoglobulin A Measurement for Intestinal Mucosal Health Assessment in Wild Lemurs.

The measurement of biomarkers in blood and excreta can enable immune status assessment and provide prognostic information on individual health outcomes. In this respect, the fecal measurement of secretory immunoglobulin A (sIgA), the primary mammalian antibody for mucosal defense, has recently received increased interest in a few anthropoid primates, but a fecal sIgA assay for use in strepsirrhine primates has not yet been reported. Here, we develop and analytically validate a cost-effective in-house sandwich enzyme immunoassay for the extraction and measurement of sIgA in feces of redfronted lemurs (Eulemur rufifrons). We also tested a simple method for sIgA extraction that can be used under remote field conditions and undertook experiments to assess the robustness of sIgA concentrations to variation in processing and storage conditions of fecal extracts. Our analytical validation revealed that the assay recognizes immunoreactive sIgA in redfronted lemur feces, that sIgA can be measured accurately with no potential interference from the fecal matrix, and that assay reagents and performance are highly stable over time. The field-friendly extraction procedure produced sIgA results strongly correlated with those generated by a standard laboratory extraction method. Short-term storage at room temperature resulted in a slight decline in sIgA concentrations, whereas freezing extracts at -20°C kept sIgA levels stable for at least 3 months. Longer-term storage of >5 months, however, led to a significant decline of sIgA concentrations. Multiple freeze-thaw cycles did not affect sIgA levels. This study, therefore, provides the basis for measuring fecal sIgA in lemurs and possibly other strepsirrhines. When samples are processed properly and stored frozen, and when sIgA analysis can be performed within 3 months upon sample collection, fecal sIgA measurements can become a valuable tool for monitoring aspects of immunity and health in both zoo-housed and wild-living lemurs.

Use of intravenous immunoglobulin in antiphospholipid antibody positive patients with high risk of miscarriage: a systematic review and meta-analysis.

Objective: The purpose of the present study was to evaluate whether intravenous immunoglobulin (IVIG) increases live birth rates and improves neonatal results in patients with antiphospholipid antibodies (aPL) at high-risk for miscarriage. Background: Positivity of aPL in pregnant women is a high-risk factor for miscarriage, and IVIG treatment has emerged as a potential intervention. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was employed to search multiple electronic databases for articles published until August 20, 2023, including PubMed, Web of Science, Embase, Scopus and Medline. The inclusion criteria encompassed studies assessing the efficacy of IVIG in aPL-positive patients with a high risk of miscarriage. Relevant articles were assessed for the quality and data were extracted for analysis. Two independent reviewers performed study selection, data extraction, and quality assessments. The risk of bias was evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.3. Results: This systematic review included nine randomized controlled trials, with 366 aPL-positive women at high risk of miscarriage. These studies included in this review were randomized controlled trials. The primary outcome measures were successful pregnancy outcomes and live birth rates. The secondary outcomes included obstetric complications, and neonatal outcomes (such as birth weight and live-birth rate). The comparison between the intervention and control groups revealed no significant differences in terms of obstetric complications and neonatal outcomes. The group receiving IVIG treatment had a higher prevalence of preterm deliveries than controls (OR = 2.05, I2 = 46%, 95% CI [0.58-5.24]), but also exhibited a partial improvement in live birth rates (OR = 2.86, I2 = 52%, 95% CI [1.04-7.90]), because it reduced the number of miscarriages (OR = 0.35, I2 = 52%, 95% CI [0.13-0.96]). Conclusion: Based on the available evidence, IVIG intervention appears to be a potentially effective approach for managing of aPL-positive pregnant women with high risk of miscarriage. While IVIG shows significant potential in tripling the chances of having a live-born child, further large-scale randomized controlled trials are necessary, preferably comparing IVIG with hydroxychloroquine or lifestyle and dietary interventions, to refine treatment protocols and ensure the most effective application.

A clinical case of B-cell lymphoma in a Japanese Black cow with monoclonal proliferation of B-cells as revealed by polymerase chain reaction based on the immunoglobulin light chain gene.

A 35-month-old Japanese Black cow was presented to a local veterinarian with a main complaint of premature labor. There was no swelling of lymph nodes on the body surface and no palpable mass on rectal examination. Although atypical lymphocytes were observed in the peripheral blood, no lymphocytosis was recorded. On Day 12, the cow developed hindlimb paresis and was euthanized. Necropsy revealed swelling of some lymph nodes, and white nodules in uterus and right atrial appendage. Histopathological examination revealed B-cell lymphoma. In clonality analysis of peripheral blood and tumor tissue, monoclonal proliferation was detected by PCR for immunoglobulin light chain (IgL) λ, suggesting neoplastic proliferation of B-cell. IgL-PCR is thought to be a possible tool for diagnosis of B-cell lymphoma.

Diagnosis and Clinical Management of Drug Allergies in Obstetrics and Gynecology: An Expert Review.

Drug allergies, specifically antibiotic allergies, are frequently encountered in obstetrics and gynecology as10% of the United States population reports a penicillin allergy. This poses a particular challenge to the obstetrician-gynecologist as beta-lactam antibiotics are indicated as first-line therapy for the treatment and prevention of most specialty-specific infections. Alternative antibiotic use in the setting of a reported allergy, is not benign and has been associated with increased cesarean delivery, endometritis, wound complications, and increased lengths of hospital stay in pregnant patients, increased Group B Streptococcus sepsis, neonatal length of stay and neonatal lab draws in neonates born to allergic patients and increased surgical site infections in gynecologic patients. Furthermore, alternative antibiotic use leads to increased antibiotic resistance, toxicity and healthcare cost. . Administration of antibiotics in a patient with a history of a Type I immediate hypersensitivity reaction, however, poses the risk of anaphylaxis with repeat exposure. Fortunately, over 90% of patients who report a penicillin allergy are not truly allergic and would tolerate penicillins if administered. This can be due to either mislabeling of the index reaction as an allergy (when it was due to a drug intolerance or a viral exanthem) or due to waning Immunoglobulin E-mediated immunity over time. Given this, allergy evaluation is widely recommended, even in pregnancy. Allergy evaluation involves a detailed patient history and when appropriate allergy testing with skin testing and/or oral challenge. These tools when used appropriately have been found to be safe and effective in gravid as well as non-gravid individuals and result in increased use of first line antibiotics. Furthermore, even in the setting of a true penicillin allergy, cross-reactivity with cephalosporins is extremely low and estimated at 2-3% among patients with a verified penicillin allergy and significantly lower than this among patients with an unverified penicillin allergy. Guidelines support routine use of cephalosporins without testing or additional precautions in patients with an unverified nonanaphylactic penicillin allergy as well as routine use of structurally dissimilar cephalosporins (specifically ancef) even in patients with an anaphylactic penicillin allergy. In cases where there is no appropriate alternative antibiotic than to the one which the patient is allergic such as with syphilis in a penicillin allergic pregnant patient, desensitization can be performed. This process involves temporary induction of drug tolerance through exposure of small amounts of the allergen until a therapeutic dose is achieved and has been safely performed in pregnancy. Desensitization requires expert supervision and is most often performed in the intensive care setting with a multidisciplinary team. The other two most common antibiotic allergies encountered in obstetrics and gynecology are to cephalosporins and metronidazole. Cephalosporin allergies are managed similarly to penicillin allergies with readily available skin testing and oral challenge. Skin testing for metronidazole allergy lacks sensitivity and specificity and thus oral challenge or desensitization procedure is the preferred approach for low risk and high-risk patients respectively. When it comes to drug allergies, and specifically antibiotic allergies, the role of the obstetrician-gynecologist is to identify patients with a reported allergy and to refer patients to a specialist for further evaluation as soon as possible. Allergy evaluation by means of a detailed patient history and allergy testing (skin testing and/or oral challenge) when indicated has been shown to be safe and effective and is an important part of antibiotic stewardship.

A systematic review of total IgE reference intervals - A 2024 update.

BACKGROUND: Total IgE (tIgE) is a frequently requested analyte in patients presenting with symptoms of atopy. Although tIgE has limited clinical utility in the diagnosis of atopic diseases, it is still important that appropriate reference intervals are provided to the intepreting clinician. Concerns have recently been raised whether laboratories are using outdated tIgE reference intervals. The aim of this study was therefore to perform the first systematic literature review of tIgE reference intervals to aid laboratories in choosing appropriate sources of tIgE reference intervals. METHODS: A search was performed in MEDLINE, Embase and the Cochrane Library from time of inception to July 2024. Eligible studies had to provide an estimate of paediatric and/or adult tIgE reference intervals using current generation immunoassays. The methodology followed PRISMA guidelines, and the study protocol was registered in the PROSPERO database (CRD42023396441). RESULTS: A total of 1667 records were screened of which 20 studies remained after the full text review. The studies included 23 910 individuals and covered 18 countries. Upper reference limits varied significantly, with participant selection (inclusion or exclusion of in vitro confirmed specific IgE sensitised individuals) and statistical methods identified as the most important factors influencing the upper reference limit. CONCLUSION: This review emphasises the need for laboratories to carefully evaluate the participant selection criteria and employed statistical methods whilst determining which tIgE reference intervals are the most appropriate to report to clinicians. Further efforts should also be made to harmonise and improve the reporting of tIgE reference interval studies.

Intravenous immunoglobulin­based adjuvant therapy for severe fever with thrombocytopenia syndrome: A single­center retrospective cohort study.

Intravenous immunoglobulin (IVIG) is frequently administered to patients with severe fever with thrombocytopenia syndrome (SFTS), particularly those with severe manifestations, although its efficacy remains controversial. The study retrospectively analyzed the effects of IVIG administration on SFTS patients in both mild and severe groups. The primary outcome measure was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. A total of SFTS patients with complete data enrolled from January 1, 2015, to August 1, 2023. Death at 28 days occurred for 68 (17.5%) patients. By unadjusted analysis, no difference was observed for 28-day mortality between the IVIG and non-IVIG groups in both the mild and severe groups. Similar results were found by propensity score matching and by IPTW analysis. Although IVIG is frequently used as adjuvant therapy for severe SFTS patients, no significant association was observed between IVIG treatment and reduced mortality in this patient population.

An unbiased comparison of immunoglobulin sequence aligners.

Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is critical for our understanding of the adaptive immune system's dynamics in health and disease. Reliable analysis of AIRR-seq data depends on accurate rearranged immunoglobulin (Ig) sequence alignment. Various Ig sequence aligners exist, but there is no unified benchmarking standard representing the complexities of AIRR-seq data, obscuring objective comparisons of aligners across tasks. Here, we introduce GenAIRR, a modular simulation framework for generating Ig sequences alongside their ground truths. GenAIRR realistically simulates the intricacies of V(D)J recombination, somatic hypermutation, and an array of sequence corruptions. We comprehensively assessed prominent Ig sequence aligners across various metrics, unveiling unique performance characteristics for each aligner. The GenAIRR-produced datasets, combined with the proposed rigorous evaluation criteria, establish a solid basis for unbiased benchmarking of immunogenetics computational tools. It sets up the ground for further improving the crucial task of Ig sequence alignment, ultimately enhancing our understanding of adaptive immunity.

Guillain-Barré syndrome in pregnancy: a case report and review of the literature.

Guillain-Barré syndrome represents a heterogeneous group of immune-mediated peripheral neuropathies that are characterized by various clinical manifestations. Reporting this clinical case emphasizes the rarity of Guillain-Barré syndrome, the diagnostic challenges faced by healthcare providers, and the risk of delayed diagnosis for both the mother and fetus. A 34-year-old pregnant woman at 33 weeks of gestation presented to the inpatient ward complaining of paresthesia in the lower and upper limbs, muscle pain, balance disturbances, moderate headache, nausea and vertigo, general weakness, and pronounced fatigue. The patient had experienced an acute viral respiratory infection 4 weeks before presenting to the hospital. The patient was admitted to the intensive care unit with a preliminary diagnosis of acute viral respiratory infection and nasopharyngitis. The patient's condition worsened dynamically, manifesting bulbar syndrome (swallowing problems), paresthesia of the anterior abdominal wall, reduced perception of fetal movements, numbness of the tongue, and low fever (37.2°C). A diagnosis of acute inflammatory demyelinating polyradiculopathy (Guillain-Barré syndrome) was established. Despite treatment, the neurologic symptoms worsened. The paravertebral radicular type pains were difficult to manage with administered analgesic therapy, and there was a progression of the bulbar syndrome. Treatment with intravenous immunoglobulin was initiated. Consequently, it was recommended by the multidisciplinary council to perform an emergency cesarean delivery, in the interest of the mother and fetus. Guillain-Barré syndrome is a rare condition that occurs during pregnancy and requires thorough evaluation, prompt multidisciplinary assessment, and individualized management of delivery to improve maternal and fetal prognosis.

Role of specific immunoglobulin-E in chronic rhinosinusitis: Its clinical relevance according to nasal challenge test.

Background: Guidelines for chronic rhinosinusitis (CRS) propose total IgE and eosinophils as important biomarkers to identify type-2 inflammation. Despite the fact that specific IgE (sIgE) have been identified as a clinical predictor in some type-2 diseases for different clinical outcomes, its role in CRS has yet to be explored in detail. Objetive: To describe systemic and local sIgE in CRS and explore its possible association with clinical outcomes using nasal challenge tests (NCT). Methods: In CRS patients, we measure total IgE, serum sIgE (SsIgE) and nasosinusal sIgE (NsIgE) against 9 allergenic sources; Der p, Der f, Blo t, Can f, Fel d, Per a, grasses, Staphylococcus enterotoxin A, and B. NCT was done using the allergen with the higher sIgE prevalence (Der p). Results: A total of 174 patients were included. Prevalence of SsIgE was 52.8% and NsIgE 46.5%; Der p was the principal allergen for SsIgE and NsIgE. The presence of nasal polyps, asthma comorbidity, NSAID hypersensitivity, and hyposmia, were significantly associated with the presence of SsIgE and NsIgE but not with total IgE. NCT-Der p was performed in 73 CRS patients, being positive in 33 (45.2%). SsIgE have the best diagnostic accuracy (79.4%) to predict NCT results (NsIgE 67.5% total IgE 52%). Conclusion: Specific IgE is a better biomarker in CRS than total IgE. Patients with clinically relevant SsIgE have a pheno-endotype associated with different clinical outcomes. Considering the clinical relevance of SsIgE demonstrated by NCT, interventions like allergen immunotherapy in CRS must be study.

[Non-amyloid tissue deposits of monoclonal immunoglobulin (excluding renal involvement)]. / Dépôts tissulaires non amyloïdes d'immunoglobuline monoclonale (hors atteinte rénale).

Monoclonal immunoglobulins can form deposits other than amyloidosis in various tissues. Immunofluorescence is the key analysis for the identification of monoclonal immunoglobulin deposits. Pulmonary light chain deposition disease is a diagnosis to be considered when dealing with diffuse cystic lung disease.

Immunoparesis recovery in newly diagnosed transplant ineligible multiple myeloma patients, an independent prognostic factor that complements minimal residual disease.

Information on the prognostic value of immunoparesis (IP) recovery in multiple myeloma (MM) patients has been only generated in some observational and retrospective studies. We have evaluated the prognostic impact of IP recovery and its association with minimal residual disease (MRD) in a series of 113 newly diagnosed transplant-ineligible (NDTI) patients, that received fix duration treatment (18 cycles of VMP/lenalidomide-dexamethasone) within the PETHEMA/GEM2010MAS65 trial and who achieved CR or VGPR. Immunoglobulin levels were measured at diagnosis, at the end of treatment (after cycle 18th) and during subsequent follow up whereas MRD was analyzed only at the end of the treatment (after cycle 18th). We found that patients who had IP at diagnosis and recovered it during or after treatment had longer progression free survival (PFS) [p < 0.001; HR 0.32 (0.19-0.52)] and longer overall survival (OS) [p = 0.007; HR 0.40 (0.20-0.80)] compared to those who failed to recover it. When we analyzed IP recovery in MRD negative patients, we found that those cases with IP recovery had longer PFS [p = 0.007; HR 0.31 (0.13-0.76)] and longer OS [p = 0.012; HR 0.21 (0.06-0.80)] as compared to MRD negative patients but without IP recovery. In conclusion, IP recovery confers better prognosis in NDTI-MM patients with fixed duration treatment who achieve CR or VGPR and the prognostic value of MRD can be complemented when combined with IP recovery.