Search Results (37)

Florid cemento-osseous dysplasia (FCOD) is a benign fibro-osseous condition typically presenting as multifocal, sclerotic masses throughout the jaws. While often asymptomatic, the hypovascular nature of the dysplastic bone predisposes it to secondary infection, which can mimic more aggressive pathologies. We present a complex diagnostic challenge involving a 76-year-old female with a history of intravenous ibandronic acid therapy for 18 months. The patient presented with a purulent mandibular fistula and exposed bone, leading to an initial clinical suspicion of Stage 2 Medication-Related Osteonecrosis of the Jaw (MRONJ). Radiographic evaluation, however, revealed generalized “cotton-wool” opacities across all four quadrants, characteristic of FCOD, with multifocal mixed radiolucent–radiopaque changes and a localized demarcated sequestrum in the symptomatic area. Accordingly, the diagnostic reasoning progressed from an initial clinical suspicion of MRONJ, to radiologic consideration of infected FCOD, and finally to exclusion of plasma cell neoplasia by immunohistochemical evaluation. The diagnostic dilemma intensified during histopathological analysis, which revealed an unusually dense, sheet-like infiltration of plasma cells within the fibro-osseous stroma. This striking plasmacytosis initially raised suspicion for a plasma cell neoplasm, such as plasmacytoma or multiple myeloma. To differentiate reactive inflammation from malignancy, immunohistochemical staining for kappa and lambda light chains was performed, demonstrating a polyclonal pattern that confirmed a reactive process. The final diagnosis was determined as FCOD with superimposed secondary osteomyelitis. Following conservative surgical debridement and targeted antibiotic therapy, the patient showed clinical resolution and remained stable at a 6-month follow-up. Recognizing these overlaps is essential for preventing over-treatment and ensuring appropriate management in elderly patients with complex medical backgrounds. Full article

Background/Objectives: T-cell lymphomas are relatively common in veterinary species, yet current diagnostic tools such as PCR-based clonality assays often lack sensitivity and specificity. In humans, we recently developed two related tissue-based diagnostic approaches based on the differential detection of the mutually exclusively expressed TCRbeta1 and 2 (TCRβ1 and 2) constant region proteins, or the corresponding TRBC1 and TRBC2 transcripts. Analogous to the detection of kappa/lambda light chains for the diagnosis of B-cell/plasma cell neoplasms in human clinical practice, our TCRβ1/2 diagnostic assay has the potential to transform veterinary diagnostic workflows. Methods: We identified and confirmed the sequences of the relevant TRBC1 and TRBC2 sequences in both cats and dogs, focusing on the 3′ untranslated region (UTR), where there is the least sequence homology between TRBC1 and TRBC2. To allow us to design appropriate probe sequences, we confirmed a lack of 3′UTR in either species, and we observed limited 3′ untranslated region UTR sequence polymorphism in the cat but not in the dog 3′UTR. We designed BaseScope™ RNA in situ hybridization probes targeting the 3′ UTR to distinguish between TRBC1 and TRBC2 transcripts in formalin-fixed paraffin-embedded tissues. Results: In normal tissues, we found the TRBC2:TRBC1 expression ratio to be similar to the 1.2:1 ratio in humans, between 1:1 and 3:1, skewing towards TRBC2, in both dogs and cats. These findings were corroborated using quantitative reverse transcription PCR. Applying our in situ hybridization probes to cases of T-cell lymphoma in dogs and cats, we demonstrated that an assay for differential expression of TRBC1 and TRBC2 in T-cell populations could identify clonal T-cell populations, as in human diagnostics. If further studies corroborate this proof-of-concept study, TRBC1/2 detection could obviate the need for slow, complex and expensive multiplexed PCR-based (PCR for antigen receptor rearrangements (PARR)) clonality assays. Conclusions: This study provides proof-of-concept data for a novel diagnostic approach that could simplify and substantially improve the accuracy of lymphoma diagnostics in veterinary medicine, by detecting TRBC1/2 transcripts. Full article

Background: Long COVID remains a challenging and heterogeneous condition, with mechanisms that are still incompletely understood. Emerging evidence suggests that patients with allergic disease may experience more persistent post-COVID symptoms, possibly due to immune dysregulation and epithelial barrier fragility. Methods: We carried out an observational, single-center study at the Allergy and Clinical Immunology Unit of Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). Seventeen adults with confirmed allergic disease and long COVID were evaluated between July and December 2024. Biomarkers reflecting allergic inflammation and barrier integrity, blood eosinophil count, total immunoglobulin E (IgE), eosinophil cationic protein (ECP), and serum free light chains (FLCs), were measured and analyzed for interrelationships and symptom correlations. Results: Participants (10 men, 7 women; mean age 43.7 years) showed variable biomarker profiles, consistent with the heterogeneity of allergic inflammation. Mean eosinophil count was 179 ± 72 cells/µL, total IgE 165.4 ± 140.6 kU/L, ECP 64.2 ± 48.5 ng/mL, and the kappa/lambda FLC ratio 1.20 ± 0.69. Notably, elevated kappa FLC levels (>19.4 mg/L) were significantly associated with high ECP (>20 ng/mL) (χ² = 10.6, p = 0.001) and increased IgE (>200 kU/L) (χ² = 6.0, p = 0.015). Individuals with higher ECP and FLCs more often reported respiratory and systemic symptoms, especially fatigue, dyspnea, and cognitive fog, that persisted beyond six months. Conclusions: These findings suggest that biomarkers of allergic inflammation and barrier dysfunction, particularly ECP and FLCs, may contribute to the persistence of long-COVID symptoms in allergic patients. The observed links between humoral activation, eosinophilic activity, and prolonged symptom burden support a model of sustained inflammation and delayed epithelial recovery. Larger, longitudinal studies including non-allergic controls are warranted to confirm these associations and to explore whether restoring barrier integrity could shorten recovery trajectories in this vulnerable population. Full article

Background and objectives: Cast nephropathy is the main cause of acute renal failure in patients with multiple myeloma. There are conflicting data on whether removal of serum free light chains (sFLCs) with a high-cutoff (HCO) dialyzer has a favorable effect on the recovery of renal function. This may in part be explained by differences in the efficacy of sFLC removal by HCO dialysis and treatment responses to anti-plasma cell therapy between studies. We studied the removal of sFLCs during HCO treatment in detail in relation to treatment response. Materials and methods: Pre-dialysis serum and dialysate levels of sFLCs were simultaneously and repeatedly measured during the first two HCO treatments in 10 patients with kappa (κ)- and 5 patients with lambda (λ)-producing myeloma that presented with dialysis-dependent renal failure at our institution between 2009 and 2024. Results: The average change in sFLCs during 6 h treatments was −57 ± 13%, but it varied widely between −29% and −77%. Mean reductions in sFLCs were comparable for κ and λ (−61.4 ± 19.1% and −55 ± 16.7%, respectively; p = 0.78). The average clearance of sFLCs at 15 min after the start of HCO dialysis was 42.1 ± 8.5 and 27.4 ± 15.6 mL/min for κ and λ, respectively (p < 0.01). Clearances decreased to 27.2 ± 11.3 for κ and 13.8 ± 7.9 mL/min for λ after 6 h of HCO treatment (p = 0.042). Renal function recovered in 11 patients (73%). In three of the four patients whose renal function did not recover, sFLC levels were >5 g/L at any time beyond 2 weeks after the start of HCO treatment. Conclusions: Although the clearance of κ was higher compared to λ, reductions in sFLCs were similar for κ and λ. We speculate that this discrepancy is explained by greater adherence of λ to the HCO membrane. Patients whose renal function did not recover had less of a reduction in sFLC levels during HCO treatment, probably due to a suboptimal hematological response to anti-plasma cell therapy. Full article

Introduction: Expanded hemodialysis using medium cut-off (MCO) dialyzers effectively removes middle-molecule uremic toxins, comparable to hemodiafiltration, but their single-use designation increases the dialysis costs. This study evaluated the efficacy and safety of reusing two MCO dialyzers available in Thailand. Methods: In this randomized controlled trial, hemodialysis patients were assigned to receive treatment with either Theranova^® 500 or Elisio^® 21HX dialyzers. Each dialyzer was reprocessed using peracetic acid and reused for up to 15 sessions. Dialyzer performance was assessed by the reduction ratios (RRs) of solutes, including β2-microglobulin (β2-MG), kappa and lambda free light chains (κ-FLC, λ-FLC), and interleukin-6 (IL-6), at baseline and the 2nd, 5th, 10th, and 15th sessions. Results: Forty-eight patients were enrolled (mean age 63.6 ± 13.7 years; 62.5% male) and randomized into 2 groups with comparable baseline characteristics. RRs for β2-MG, κ-FLC, and λ-FLC were similar between the groups and declined modestly over time after dialyzer reused (β2-MG: 78.2% to 72.5% vs. 77.2% to 74.5%, κ-FLC: 64.6% to 51.3% vs. 58.9% to 49.5%, and λ-FLC: 51.2% to 46.4% vs. 49.4% to 39.2% in the Theranova^® 500 and Elisio^® 21HX groups, respectively). Theranova^® 500 demonstrated significantly higher IL-6 clearance in the 2nd (29.9% vs. 16.0%; p = 0.018) and 5th (23.8% vs. 7.7%, p = 0.031) sessions. It also showed a non-significant trend toward lower dialyzer survival (HR 3.98; p = 0.085) and higher, though clinically acceptable, albumin loss (mean difference 0.56 g/session; p < 0.001), which decreased with reuse. Conclusions: Both MCO dialyzers demonstrated comparable overall performance during reuse. Theranova^® 500 provided better IL-6 clearance with manageable albumin loss. Implementation of high-quality dialyzer reuse protocols may optimize clinical efficacy and patient outcomes while balancing cost, accessibility, and environmental considerations. Full article

Background/Objectives: Plasma cell gingivitis (PCG) is a rare, benign, non-dental-plaque-induced inflammatory condition characterized by dense subepithelial infiltration of polyclonal plasma cells. Due to its nonspecific clinical presentation, PCG represents a diagnostic challenge. This case report aims to describe a clinical case of PCG, highlighting the diagnostic process, histopathological correlation, and therapeutic approach. Methods: A 57-year-old male presented with a polypoid, erythematous, and edematous gingival lesion in the anterior maxillary region, with spontaneous bleeding on probing. Following clinic assessment, an incisional biopsy was performed, alongside complete hematological and inflammatory profiling. Histological and immunohistochemical analyses revealed the presence of an inflammatory infiltrate. Results: Histological evaluation revealed spongiotic squamous epithelium characterized by a dense plasma cell infiltrate with a liquenoid pattern of CD3-positive T and CD20-positive B lymphocytes. A polytypic expression of kappa and lambda light chains was also detected. The patient underwent topical corticosteroid therapy, showing progressive clinical improvement and resolution of symptoms, although minor mucosal involvement persisted. Conclusions: PCG remains a rare and underdiagnosed condition requiring integration of clinical, hematological, and histopathological data for accurate diagnosis. While corticosteroids remain the first-line therapy, emerging treatments, including photobiomodulation, may offer future adjunctive strategies to improve outcomes and reduce recurrence. Full article

Background and Clinical Significance: Membranoproliferative glomerulonephritis (MPGN) is a rare and heterogeneous pattern of immune-mediated glomerular injury, often associated with infections, autoimmune disorders, or monoclonal gammopathies. Idiopathic cases remain a diagnostic challenge and frequently require empirical immunosuppressive treatment. There is increasing interest in environmental triggers that may activate the immune system in genetically or immunologically predisposed individuals. We report an unusual case of idiopathic immune complex-mediated MPGN with a relapsing course potentially associated with vaccine-induced immune reactivation. Case Presentation: A 35-year-old male with no significant medical history aside from untreated dyslipidemia and active smoking presented with a hypertensive emergency and acute kidney injury (AKI). Laboratory investigations revealed nephrotic-range proteinuria, microscopic hematuria, and reduced estimated glomerular filtration rate (eGFR). Kidney biopsy demonstrated type I immune complex-mediated MPGN with a diffuse endocapillary proliferative pattern and granular subendothelial deposits (IgG+++, C3+++, C1q++). An extensive work-up ruled out secondary causes, supporting a diagnosis of idiopathic MPGN. Immunosuppressive therapy with corticosteroids and mycophenolate mofetil led to a partial clinical response. However, after receiving multiple vaccinations, the patient experienced clinical deterioration. A second biopsy revealed persistent proliferative changes and new deposits of IgM++, C4d++, and both kappa and lambda light chains. This prompted a reintroduction of immunosuppressive therapy, which resulted in subsequent clinical improvement. Conclusions: This case supports the hypothesis that vaccine-induced immune reactivation may serve as a potential trigger for disease relapse in idiopathic MPGN. Clinicians should remain alert to environmental stimuli that may influence disease activity in immune-mediated glomerulopathies. Further research is needed to elucidate the underlying immunopathogenic mechanisms. Full article

Recombinantly produced monoclonal antibodies (mabs) belong to the fastest growing class of biotherapeutics. In humans, antibodies are classified into five different classes: IgA, IgD, IgE, IgG and IgM. Most of the therapeutic mabs used in the clinic belong to the IgG class, albeit other antibody classes, e.g., IgM, have been evaluated in clinical stages. Antibodies are composed of heavy chains paired with a light chain. In IgM and IgA, an additional chain, the J-chain, is present. Two types of light chains exist in humans: the κ-light chain and the λ-light chain. The κ-light chain predominates in humans and is used in the vast majority of therapeutic IgG. The reason for the preference of the κ-light chain in humans is not known. Our study investigates whether light-chain selection influences the productivity of the clinically validated mabs adalimumab and trastuzumab. Both mabs were expressed as IgG and IgM with a κ- or a λ-light chain in HEK293 cells. Besides comparing the expression levels of the different mabs, we also evaluated whether the passage number of the cell line has an impact on product yield. In addition, the expressions of adalimumab, trastuzumab, an anti-CD38 and an anti-PD-L1-antibody were analyzed in HEK293 and CHO cells when both the κ- and λ-light chains are present. In summary, IgG outperformed IgM variants in expression efficacy, while light-chain selection had minimal impact on the overall expression levels. The yields of all mab variants were higher in fresh cells, despite cell cultures with a high cell passage number having higher cell densities and cell numbers at the time of harvest. The incorporation of a particular light chain occurred at similar rates in HEK293 and CHO cells. Full article

Therapeutic antibodies with lambda light chains (λ-Abs) are underrepresented compared to kappa light chains (κ-Abs). Here, we evaluated two SARS-CoV-2-specific monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding as κ and λ variants. mAbs expressed in glycoengineered Nicotiana benthamiana did not show differences in expression levels, glycosylation, and antigen binding, while κ-Abs exhibited slightly increased thermodynamic stability over λ-Abs. SARS-CoV-2 neutralization and IgG-FcγR immune complex studies revealed increased activities of H4 IgG1κ compared to H4 IgG1λ, with no differences observed between P5C3 variants. Our results indicate that constant light chain variability and Ab specificity contribute to Ab features, a fact that should be considered in engineering therapeutics. Full article

Background/Objectives: Lung cancer screening can reduce patient mortality. Multiple issues persist including timely management of patients with a radiologically defined indeterminate pulmonary nodule (IPN), which carries unknown pathological significance. This pilot study focused on combining demographic, clinical, radiographic, and common circulating biomarkers for their ability to aid in IPN risk of malignancy prediction. Methods: A case-control cohort consisting of 379 patients with IPNs (251 stage I lung tumors and 128 nonmalignant nodules) was used for this effort, divided into training (70%) and testing (30%) sets. Demographic variables (age, sex, race, ethnicity), radiographic information (nodule size and location), smoking pack-years, and plasma biomarker levels of CA-125, SCC, CEA, HE4, ProGRP, NSE, Cyfra 21-1, IL-6, PlGF, sFlt-1, hs-CRP, Ferritin, IgG, IgE, IgM, IgA, and Kappa and Lambda Free Light Chains were assessed for this purpose. Results: Multivariable analyses of biomarker, demographic, and radiographic variables yielded a model consisting of age, lesion size, pack-years, history of extrathoracic cancer, upper lobe location, spiculation, hs-CRP, NSE, Ferritin, and CA-125 (AUC = 0.872 in training, 0.842 in testing) with superior performance over the Mayo Score model, which consists of age, lesion size, history of smoking, history of extrathoracic cancer, upper lobe location, and spiculation (AUC = 0.816 in training, 0.787 in testing). Conclusions: In conclusion, a simple reduced algorithm consisting of biomarkers, clinical information, and demographic variables may have value for malignancy prediction of screen-detected IPNs. Upon further validation, this method stands to reduce the need for serial radiographic studies and the risks of diagnostic delay. Full article

Background: A 69-year-old man with multiple myeloma and left-sided heart failure presented to the hospital with a two-month fever. Method: A transjugular liver biopsy was performed due to the rapid progression of liver failure. The procedure was complicated by an intraperitoneal hemorrhage. The bleeding was managed expectantly. Result: Significantly elevated serum bilirubin levels occurred on the 13th day after liver biopsy. Increasing serum bilirubin levels were observed until the patient’s death due to a biliovenous fistula at the liver biopsy site. Simultaneously, his slightly elevated liver enzymes returned to normal. The patient died 23 days after liver biopsy due to acute respiratory distress syndrome. Fistulous communication between the biliary tree and the hepatic venous system with subsequent bile leakage into the venous system (bilhemia) can lead to bile deposition in the lungs. Bile deposition in the lungs may potentiate and accelerate the development of diffuse alveolar damage with hyaline membranes. Conclusions: Lambda and kappa light chain deposition in the pulmonary alveoli in patients with multiple myeloma can mimic typical hyaline membranes. Full article

The pathophysiology of cognitive impairment (CI) in multiple sclerosis (MS) remains unclear. Meningeal B cell aggregates may contribute to cortical grey matter pathology. Cerebrospinal fluid (CSF), kappa free light chains (KFLC), and KFLCs-Index (kappa-Index) are reliable quantitative markers of intrathecal synthesis, but few data have been presented exploring the association with CI, and no data are present for lambda FLC (LFLC) in MS. We evaluated cognition using the Brief International Cognitive Assessment for MS (BICAMS) battery and collected serum and CSF at diagnosis in newly diagnosed drug-naïve MS patients. We observed that patients with impaired verbal memory and overall CI showed increased CSF KFLCs (respectively p: 0.0003 and p: 0.003) and kappa-Index (respectively p: 0.01 and p: 0.02) compared to those with normal verbal memory and no CI. Patients with CI also displayed lower CSF LFLCs (p: 0.04) and lambda-Index (p: 0.001); however, only CSF KFLC negatively correlated with normalized results of verbal memory (for age, sex, and educational levels), even after correction for EDSS (r: −0.27 p: 0.01). Finally, CSF FKLC and kappa-Index were significant predictors of verbal memory in a multivariate analysis. Our results, suggest that intrathecal B cell activity might contribute to CI development in MS patients. Full article

Background: The complementarity-determining region (CDR) of antibodies represents the most diverse region both in terms of sequence and structural characteristics, playing the most critical role in antibody recognition and binding for immune responses. Over the past decades, several numbering schemes have been introduced to define CDRs based on sequence. However, the existence of diverse numbering schemes has led to potential confusion, and a comprehensive evaluation of these schemes is lacking. Methods: We employ statistical analyses to quantify the diversity of CDRs compared to the framework regions. Results: Comparative analyses across different numbering schemes demonstrate notable variations in CDR definitions. The Kabat and AbM numbering schemes tend to incorporate more conserved residues into their CDR definitions, whereas CDRs defined by the Chothia and IMGT numbering schemes display greater diversity, sometimes missing certain loop residues. Notably, we identify a critical residue, L29, within the kappa light chain CDR1, which appears to act as a pivotal structural point within the loop. In contrast, most numbering schemes designate the topological equivalent point in the lambda light chain as L30, suggesting the need for further refinement in the current numbering schemes. Conclusions: These findings shed light on regional sequence and structural conservation within antibody sequence databases while also highlighting discrepancies stemming from different numbering schemes. These insights yield valuable guidelines for the precise delineation of antibody CDRs and the strategic design of antibody repertoires, with practical implications in developing innovative antibody-based therapeutics and diagnostics. Full article

The Hodgkin variant Richter syndrome (HvRS) is an infrequent complication occurring in 1% of lymphocytic lymphoma/chronic lymphocytic leukemia patients. We report a case of HvRS diagnosed in Sub-Saharan Africa. A 63-year-old patient was consulted for the investigation of an abdominal mass that had been evolving for 5 years prior to admission. His history revealed night sweats, 13% weight loss in 3 months and persistent pruritis. Examination revealed bilateral cervical axillary and inguinal macroadenopathies, painless abdominal distension, pruritic lesions and WHO 2 PS. The blood count showed anemia at 9.5 g/dL. Histology revealed a lymphomatous proliferation of diffuse architecture, nodular in places, with Hodgkin and Sternberg cells associated with small lymphocytes, histiocytes and eosinophilic polymorphs. Immunohistochemistry showed CD20, PAX5, BCL2, CD5, CD23 and MYC positivity; Ki67 at 10% and cyclin D1, BCL6 and CD10 negativity; CD30 positivity on Hodgkin and Sternberg cells that remained CD20 negative; difficulty interpreting CD15; EBV positivity (EBERs); and CD3 and CD5 positivity on reactive T cells. CD138 and kappa and lambda light chains were non-contributory. The extension work-up classified the patient as Ann Arbor stage III B with a Hasenclever score of 3/7. This case illustrates the difficulties in diagnosing HvRS in our countries, where the number of haematopathologists is insufficient and the technical facilities are limited. Full article

Routine immunofluorescence microscopy of glomerular immunodeposits in IgA nephropathy shows IgA, C3, and lambda light chains, and sometimes IgG, IgM, and kappa light chains. However, a previous study using high-resolution confocal microscopy showed IgG in all IgA nephropathy cases, likely representing autoantibodies specific for galactose-deficient IgA1. Here, we used high-resolution confocal microscopy to examine the composition of glomerular immunodeposits and colocalization of kappa and lambda light chains with IgA or IgG heavy chains in kidney-biopsy samples from twenty patients with IgA nephropathy, seventeen without IgG, and nine with no or trace kappa light chains by routine immunofluorescence microscopy. IgG was detected in all biopsies by high-resolution confocal microscopy. Single-optical-plane images showed similar colocalization of IgG heavy chains with kappa and lambda light chains. Colocalization of IgA heavy chains was greater with lambda light chains than with kappa light chains. Colocalization of IgG heavy chain with kappa light chains was higher than with lambda light chains in biopsies with endocapillary hypercellularity and crescents, i.e., biopsies with active lesions. We confirmed the utility of high-resolution confocal microscopy to detect components of glomerular immunodeposits not apparent on routine immunofluorescence microscopy and for colocalization of different components, potentially clarifying the pathogenesis of IgA nephropathy. Full article