Granular Deposits Research Articles

Enhancing La(III) biosorption and biomineralization with Micromonospora saelicesensis: Involvement of phosphorus and formation of monazite nano-minerals

The release of rare earth elements (REEs) from mining wastes and their applications has significant environmental implications, necessitating the development of effective prevention and reclamation strategies. The mobility of REEs in groundwater due to microorganisms has garnered considerable attention. In this study, a La(III) resistant actinobacterium, Micromonospora saelicesensis KLBMP 9669, was isolated from REE enrichment soil in GuiZhou, China, and evaluated for its ability to adsorb and biomineralize La(III). The findings demonstrated that M. saelicesensis KLBMP 9669 immobilized La(III) through the physical and chemical interactions, with immobilization being influenced by the initial La(III) concentration, biomass, and pH. The adsorption kinetics followed a pseudo-second-order rate model, and the adsorption isotherm conformed to the Langmuir model. La(III) adsorption capacity of this strain was 90 mg/g, and removal rate was 94 %. Scanning electron microscope (SEM) coupled with energy dispersive X-ray spectrometer (EDS) analysis revealed the coexistence of La(III) with C, N, O, and P. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) investigations further indicated that carboxyl, amino, carbonyl, and phosphate groups on the mycelial surface may participate in lanthanum adsorption. Transmission electron microscopy (TEM) revealed that La(III) accumulation throughout the M. saelicesensis KLBMP 9669, with some granular deposits on the mycelial surface. Selected area electron diffraction (SAED) confirmed the presence of LaPO4 crystals on the M. saelicesensis KLBMP 9669 biomass after a prolonged period of La(III) accumulation. This post-sorption nano-crystallization on the M. saelicesensis KLBMP 9669 mycelial surface is expected to play a crucial role in limiting the bioimmobilization of REEs in geological repositories.

Hepatitis B Virus-related Membranous Nephropathy with Crescentic Formation in an Inactive Carrier of Positive Hepatitis B Surface Antigen with Undetectable DNA under Anti-viral Treatment.

A man who was an inactive hepatitis B virus (HBV) carrier with positive hepatitis B surface antigen (HBs antigen) and undetectable HBV-DNA under anti-viral treatment developed nephrotic syndrome at 52 years old, and a renal biopsy revealed advanced membranous nephropathy (MN) with focal cellular crescents, interstitial hemorrhaging, and peritubular capillaritis. Immunofluorescence studies demonstrated granular IgG deposition and HBs antigen-positivity along the capillaries. Glomeruli were negative for phospholipase A2 receptor 1. There were no clinical findings of systemic vasculitis. We considered MN combined with small-vessel vasculitis due to HBV infection. These results suggest that HBV-related kidney disease should be considered even in patients with an inactive HBV carrier status under treatment.

Unbaffled mesoscale reactor coupled oscillatory flow-enhanced liquid–solid two–phase flow

Unbaffled U-shaped mesoscale oscillatory flow reactors (meso-OFRs) were developed to prevent solid deposition and prepare uniform barium sulfate (BaSO4) nanoparticles with environmental protection function. The results showed that the oscillation significantly reduced granular deposition; the greater the intensity of the oscillation, the faster it reached uniformity, and the less likely the granules were to be deposited. These results can be explained by the formation of a larger vortex size, which can strengthen the turbulent mixing of fluid in the reactor, promote the interaction and forced mixing between the liquid phase and solid particles, enhance the internal shear stress of the fluid, and contribute to the secondary suspension of solid particles and the disintegration of particle agglomeration. The prepared BaSO4 nanoparticles with oscillation were smaller in size and lower in pressure drop than those produced without oscillation, which conclusively illustrated that oscillation effectively prevented channel deposition and clogging.

Distinct involvement of the cranial and spinal nerves in progressive supranuclear palsy.

The most frequent neurodegenerative proteinopathies include diseases with deposition of misfolded tau or α-synuclein in the brain. Pathological protein aggregates in the PNS are well-recognized in α-synucleinopathies and have recently attracted attention as a diagnostic biomarker. However, there is a paucity of observations in tauopathies. To characterize the involvement of the PNS in tauopathies, we investigated tau pathology in cranial and spinal nerves (PNS-tau) in 54 tauopathy cases [progressive supranuclear palsy (PSP), n = 15; Alzheimer's disease (AD), n = 18; chronic traumatic encephalopathy (CTE), n = 5; and corticobasal degeneration (CBD), n = 6; Pick's disease, n = 9; limbic-predominant neuronal inclusion body 4-repeat tauopathy (LNT), n = 1] using immunohistochemistry, Gallyas silver staining, biochemistry, and seeding assays. Most PSP cases revealed phosphorylated and 4-repeat tau immunoreactive tau deposits in the PNS as follows: (number of tau-positive cases/available cases) cranial nerves III: 7/8 (88%); IX/X: 10/11 (91%); and XII: 6/6 (100%); anterior spinal roots: 10/10 (100%). The tau-positive inclusions in PSP often showed structures with fibrillary (neurofibrillary tangle-like) morphology in the axon that were also recognized with Gallyas silver staining. CBD cases rarely showed fine granular non-argyrophilic tau deposits. In contrast, tau pathology in the PNS was not evident in AD, CTE and Pick's disease cases. The single LNT case also showed tau pathology in the PNS. In PSP, the severity of PNS-tau involvement correlated with that of the corresponding nuclei, although, occasionally, p-tau deposits were present in the cranial nerves but not in the related brainstem nuclei. Not surprisingly, most of the PSP cases presented with eye movement disorder and bulbar symptoms, and some cases also showed lower-motor neuron signs. Using tau biosensor cells, for the first time we demonstrated seeding capacity of tau in the PNS. In conclusion, prominent PNS-tau distinguishes PSP from other tauopathies. The morphological differences of PNS-tau between PSP and CBD suggest that the tau pathology in PNS could reflect that in the central nervous system. The high frequency and early presence of tau lesions in PSP suggest that PNS-tau may have clinical and biomarker relevance.

PREDICTIVE FACTORS OF SURGICAL SUCCESS WITH THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE.

To present new morphologic features correlating with functional and anatomical outcomes of the inverted internal limiting membrane flap technique in full-thickness macular hole. A retrospective study of 51 successful and 22 failed full-thickness macular hole surgeries. In all eyes, preoperative spectral domain optical coherence tomography (SD-OCT) or swept source optical coherence tomography (SS-OCT) were reviewed. The presence of supraretinal pigment epithelium granular deposits, presence of an epiretinal membrane or epiretinal proliferation, visibility of posterior hyaloid, continuity of the interdigitation zone or external limiting membrane, presence of cystoid spaces, irregular surface of the margins of full-thickness macular hole, visibility of the suprachoroidal space, and diameters of full-thickness macular hole were analyzed. In multivariate analysis, the success of the first surgery depended solely on the absence of epiretinal membrane ( P < 0.05).In univariate analysis, the success of the first surgery was correlated moreover with the absence of preoperative supraretinal pigment epithelium granular deposits ( P = 0.0010), the absence of an epiretinal proliferation ( P = 0.0060), and the absence of an irregular border of the hole ( P = 0.010). In multivariate analysis, epiretinal membranes were a negative prognostic factor for macular hole closure when the inverted internal limiting membrane flap technique was used. Worse final visual acuity was observed in patients with primary anatomical failure, even if the hole was successfully closed during the second intervention.

Sea-blue histiocytosis

A 78-year-old woman with hypertrophic cardiomyopathy underwent a septal myomectomy and valve replacement. In the immediate postoperative period she developed shock of mixed etiology and died. At autopsy, hepatomegaly and splenomegaly were identified, with PAS and Giemsa positive intracellular ceroid granular deposits. Sea-blue histiocytosis is an extremely rare, chronic and benign deposit disease. It is characterized by hepatosplenomegaly, thrombocytopenia and lymphadenopathy. The presence of ceroid substance in granules in PAS and Giemsa stains should establish the diagnosis of suspicion.

The gut microbiota induces melanin deposits that act as substrates for fimA-mediated aggregation of Salmonella Typhimurium and enhance infection of the German cockroach vector.

When Salmonella Typhimurium is ingested by German cockroaches, the bacteria replicate in the gut and persist for at least 7 d, enabling transmission in the feces. However, the mechanisms that facilitate survival and persistence in the cockroach gut remain poorly detailed. We previously reported the formation of biofilm-like aggregate populations of S. Typhimurium in the gut of cockroaches upon ingestion. We also reported that deletion of the type-1 fimbrial subunit of S. Typhimurium, fimA, leads to a reduced bacterial load in the cockroach gut. Here, we link these observations and provide further insight into the mechanism and function of S. Typhimurium aggregation in the gut of the cockroach. We show that S. Typhimurium but not Escherichia coli forms aggregated populations in the cockroach gut, and that aggregate formation requires fimA but not the biofilm formation-related genes csgA and csgD. Furthermore, we show that S. Typhimurium aggregates are formed using small granular deposits present in the cockroach gut, which exhibit properties consistent with melanin, as substrates. These melanin deposits are prevalent in the guts of both immature and adult cockroaches from laboratory colonies and are correlated with increased gut bacterial density while being entirely absent in gnotobiotic cockroaches reared without exposure to environmental bacteria, indicating they are induced as a response to the gut microbiota. When cockroaches lacking melanin deposits in the gut are fed S. Typhimurium, they exhibit lower rates of infection than those harboring melanin deposits, demonstrating that microbiota-induced melanin deposits enhance infection of the gut of the vector. IMPORTANCE Cockroaches, including the German cockroach (Blattella germanica), can be both mechanical and biological vectors of pathogenic bacteria. Together, our data reveal a novel mechanism by which S. Typhimurium interacts with the cockroach gut and its microbiota that promotes infection of the vector. These findings exemplify the emerging but underappreciated complexity of the relationship between cockroaches and S. Typhimurium.

Athena: Specialty Certificate Examination case for generaldermatology.

This Athena concerns a 45-year-old man who presented with a 1-year history of recurrent tense fluid-filled lesions over his forearms, hands, feet and face associated with scarring and pigmentary changes. He had a history of regular alcohol intake (&amp;gt; 3 units daily). Lesion biopsy revealed a thick granular deposition of IgG along the basement membrane with thick homogeneous positivity of papillary dermal vessels for various immunoreactants (IgG, IgA, C3, IgM).

De novo membranous nephropathy in a pig-to-baboon kidney xenograft: A new xenograft glomerulopathy

De novo membranous nephropathy (dnMN) is an uncommon immune complex-mediated late complication of human kidney allografts that causes proteinuria. We report here the first case of dnMN in a pig-to-baboon kidney xenograft. The donor was a double knockout (GGTA1 and β4GalNT1) genetically engineered pig with a knockout of the growth hormone receptor and addition of 6 human transgenes (hCD46, hCD55, hTBM, hEPCR, hHO1, and hCD47). The recipient developed proteinuria at 42 days posttransplant, which progressively rose to the nephrotic-range at 106 days, associated with an increase in serum antidonor IgG. Kidney biopsies showed antibody-mediated rejection (AMR) with C4d and thrombotic microangiopathy that eventually led to graft failure at 120 days. In addition to AMR, the xenograft had diffuse, global granular deposition of C4d and IgG along the glomerular basement membrane on days 111 and 120. Electron microscopy showed extensive amorphous subepithelial electron-dense deposits with intervening spikes along the glomerular basement membrane. These findings, in analogy to human renal allografts, are interpreted as dnMN in the xenograft superimposed on AMR. The target was not identified but is hypothesized to be a pig xenoantigen expressed on podocytes. Whether dnMN will be a significant problem in other longer-term xenokidneys remains to be determined.

Introduction of a novel chimeric active immunization mouse model of PLA2R1-associated membranous nephropathy

The phospholipase A2 receptor 1 (PLA2R1) is the major target antigen in patients with membranous nephropathy (MN), an antibody-mediated autoimmune glomerular disease. Investigation of MN pathogenesis has been hampered by the lack of reliable animal models. Here, we overcome this issue by generating a transgenic mouse line expressing a chimeric PLA2R1 (chPLA2R1) consisting of three human PLA2R1 domains (cysteine-rich, fibronectin type-II and CTLD1) and seven murine PLA2R1 domains (CTLD2-8) specifically in podocytes. Mice expressing the chPLA2R1 were healthy at birth and showed no major glomerular alterations when compared to mice with a wild-type PLA2R1 status. Upon active immunization with human PLA2R1 (hPLA2R1), chPLA2R1-positive mice developed anti-hPLA2R1 antibodies, a nephrotic syndrome, and all major histological features of MN, including granular deposition of mouse IgG and complement components in immunofluorescence and subepithelial electron-dense deposits and podocyte foot process effacement in electron microscopy. In order to investigate the role of the complement system in this model, we further crossed chPLA2R1-positive mice with mice lacking the central complement component C3 (C3-/- mice). Upon immunization with hPLA2R1, chPLA2R1-positive C3-/- mice had substantially less severe albuminuria and nephrotic syndrome when compared to chPLA2R1-positive mice with a wild-type C3 status. In conclusion, we introduce a novel active immunization model of PLA2R1-associated MN and demonstrate a pathogenic role of the complement system in this model.

Tubular basement membrane deposits after allogeneic hematopoietic stem cell transplantation

BackgroundExtraglomerular immune complex deposition is rare and only a few membranous nephropathy cases with tubular basement membrane deposits have been reported following allogeneic hematopoietic stem cell transplantation.Case presentationWe reported a 56-year-old man with increased serum creatinine after allogeneic hematopoietic stem cell transplantation who underwent a renal biopsy. Tubular interstitial nephritis was identified on light microscope. The unique histologic features were diffuse tubular basement membrane immune complex deposition detected by both immunofluorescence and electron microscopy, while the glomerular involvement was inconspicuous. The differential diagnosis from other forms of tubular basement membrane deposition is discussed.ConclusionDiffuse granular tubular basement membrane immune complex deposition with minimal glomerular involvement is also a manifestation of renal complication in hematopoietic stem cell transplantation recipient. However, the exact mechanism and target antigen remains unknown.

TUNEL-positive structures in activated microglia and SQSTM1/p62-positive structures in activated astrocytes in the neurodegenerative brain of a CLN10 mouse model.

Neuronal ceroid lipofuscinosis is a group of pediatric neurodegenerative diseases. One of their causative genes, CLN10/CtsD, encodes cathepsin D, a major lysosomal protease. Central nervous system (CNS)-specific CtsD-deficient mice exhibit a neurodegenerative disease phenotype with accumulation of ceroid lipofuscins, granular osmiophilic deposits, and SQSTM1/p62. We focused on activated astrocytes and microglia in this neurodegenerative mouse brain, since there are few studies on the relationship between these accumulators and lysosomes in these glial cells. Activated microglia and astrocytes in this mouse thalamus at p24 were increased by approximately 2.5- and 4.6-fold compared with the control, while neurons were decreased by approximately half. Granular osmiophilic deposits were detected in microglial cell bodies and extended their processes in the thalamus. LAMP1-positive lysosomes, but not SQSTM1/p62 aggregates, accumulated in microglia of this mouse thalamus, whereas both lysosomes and SQSTM1/p62 aggregates accumulated in its astrocytes. TUNEL-positive signals were observed mainly in microglia, but few were observed in neurons and astrocytes. These signals were fragmented DNA from degenerated neurons engulfed by microglia or in the lysosomes of microglia. Abnormal autophagic vacuoles also accumulated in the lysosomes of microglia. Granular osmiophilic deposit-like structures localized to LAMP1-positive lysosomes in CtsD-deficient astrocytes. SQSTM1/p62-positive but LAMP1-negative membranous structures also accumulated in the astrocytes and were less condensed than typical granular osmiophilic deposits. These results suggest that CtsD deficiency leads to intracellular abnormalities in activated microglia and astrocytes in addition to neuronal degeneration.

Differential Diagnosis of Changes in Intraocular Lenses.

Differentiating between various intraocular lens (IOL) changes can be a challenge. In particular, certain IOL models carry the risk of late postoperative calcification. A major cause of IOL exchange surgery could be avoided if appropriate modifications were made during the IOL manufacturing process. The use of a hydrophilic acrylate carries the risk of IOL calcification, especially when a secondary procedure, such as a pars plana vitrectomy or other procedures using gas or air, is performed. In secondary IOL calcification, there is a wide range of opacification patterns, which are usually located in the centre on the anterior surface of the IOL or sometimes elsewhere. Often, granular deposits accumulate just below or on the surface of the IOL, leading to significant deterioration in visual quality and eventually requiring IOL exchange surgery. Therefore, in the case of eyes requiring secondary surgical intraocular intervention in the future, the use of hydrophilic IOLs should be critically evaluated. With regard to hydrophobic IOL materials, there are clear differences in the susceptibility to the formation of glistenings. Over time, there has been a significant decrease in glistening formation over the past 30years due to optimisation of the material. With hydrophobic IOLs, special care should also be taken to avoid mechanical damage. In general, the only treatment option for functionally-impairing IOL opacification is surgical lens exchange, which carries potential risks of complications. In cases with a low degree of functional impairment, and especially in eyes with additional ocular diseases, it may be difficult to weigh the risk of additional surgery against the potential benefit. In some cases, it may be more appropriate not to perform an IOL exchange despite the IOL opacification. Recent visualisation methods that allow high-resolution analysis of the opacities in vivo and in vitro may be used in the future to estimate the functional effects of various IOL material changes on the optical quality.

Altered properties of amyloidogenic prion protein in genetic Creutzfeldt-Jakob disease with PRNP V180I mutation in response to pentosan polysulfate.

Genetic Creutzfeldt-Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic CJD, and it is more difficult to detect protease-resistant prion protein in immunoblotting. However, we previously reported the autopsy case of a patient with V180I gCJD who was treated with pentosan polysulfate sodium (PPS); this case had increased protease-resistant PrP deposition. It has been suggested that PPS might reduce protease-resistant PrP; however, the detailed pharmacological and histopathological effects of PPS in humans remain unknown. We examined autopsied human brain tissue from four cases with V180I gCJD that were added to our archives between 2011 and 2021: two cases treated with PPS and two cases without PPS. We conducted a neuropathological assessment, including immunohistochemistry for PrP. We also performed immunoblotting for PrP on homogenate samples from each brain to detect protease-resistant PrP using both a conventional procedure and size-exclusion gel chromatography for the purification of oligomeric PrP. Both PPS-treated cases showed long survival time over 5 years from onset and increased PrP deposition with a characteristic pattern of coarse granular depositions and congophilic PrP microspheres, whereas the cases without PPS showed around 1-year survival from onset and relatively mild neuronal loss and synaptic PrP deposition. Although cortical gliosis seemed similar among all cases, aquaporin 4-expression as a hallmark of astrocytic function was increased predominantly in PPS cases. Immunoblotting of non-PPS cases revealed protease-resistant PrP in the oligomeric fraction only, whereas the PPS-treated cases showed clear signals using conventional procedures and in the oligomeric fraction. These unique biochemical and histopathological changes may reflect the progression of V180I gCJD and its modification by PPS, suggesting the possible existence of toxic PrP-oligomer in the pathophysiology of V180I gCJD and beneficial effects of PPS toward the aggregation and detoxication of toxic PrP-oligomer.

A deep learning-based method for detecting granular fertilizer deposition distribution patterns in centrifugal variable-rate spreader fertilization

Beginning with the problems of high cost, low efficiency and high working intensity of traditional granular fertilizer deposition distribution detection methods, this study proposes an automatic detection system of granular fertilizer deposition distribution pattern based on deep learning method. The system analyzes the distribution pattern of granular fertilizer deposition on the ground and allows for parameter calibration, performance evaluation and structural optimization of fertilizer spreading devices. In this study, hardware and software parts of the proposed system were designed. The hardware part primarily includes a customized fertilizer calibration mat, an image acquisition device, a system control terminal, and a processing core to realize image acquisition, storage, data processing, and system control functions. For the software part, a granular fertilizer identification algorithm was designed; in addition, the granular fertilizer instance segmentation network model F-TPP (Fertilizer-Swin Transformer PANet partition) was proposed that integrated the Swin Transformer network and path aggregation network (PANet) to address the problems associated with extremely small and relatively dense targets in the detection of granular fertilizers. Moreover, the F-TPP network model optimized the Anchor generation scale for appropriate segmentation detection of granular fertilizers. The experimental results show that the F-TPP network model outperformed comparison conventional network models, such as Mask R-CNN, SOLO, and YOLOv5. Indeed, the detection efficiency of the proposed model was higher than that of conventional models for small and dense granular fertilizers. The proposed model yielded a detection precision, recall rate, and F1 score of 93.8%, 96.3%, and 0.95, respectively. The F-TPP network model improves the segmentation precision of granular fertilizer; thus, it improves the accuracy of automatically-deposited fertilizers. According to the experimental results, the proposed detection method yielded maximum absolute and relative errors of 0.59 g and 5.25%, respectively.

Development of a multiple convolutional neural network-facilitated diagnostic screening program for immunofluorescence images of IgA nephropathy and idiopathic membranous nephropathy.

Immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN) are the most common glomerular diseases. Immunofluorescence (IF) tests of renal tissues are crucial for the diagnosis. We developed a multiple convolutional neural network (CNN)-facilitated diagnostic program to assist the IF diagnosis of IgAN and IMN. The diagnostic program consisted of four parts: a CNN trained as a glomeruli detection module, an IF intensity comparator, dual-CNN (D-CNN) trained as a deposition appearance and location classifier and a post-processing module. A total of 1573 glomerular IF images from 1009 patients with glomerular diseases were used for the training and validation of the diagnostic program. A total of 1610 images of 426 patients from different hospitals were used as test datasets. The performance of the diagnostic program was compared with nephropathologists. In >90% of the tested images, the glomerulus location module achieved an intersection over union >0.8. The accuracy of the D-CNN in recognizing irregular granular mesangial deposition and fine granular deposition along the glomerular basement membrane was 96.1% and 93.3%, respectively. As for the diagnostic program, the accuracy, sensitivity and specificity of diagnosing suspected IgAN were 97.6%, 94.4% and 96.0%, respectively. The accuracy, sensitivity and specificity of diagnosing suspected IMN were 91.7%, 88.9% and 95.8%, respectively. The corresponding areas under the curve (AUCs) were 0.983 and 0.935. When tested with images from the outside hospital, the diagnostic program showed stable performance. The AUCs for diagnosing suspected IgAN and IMN were 0.972 and 0.948, respectively. Compared with inexperienced nephropathologists, the program showed better performance. The proposed diagnostic program could assist the IF diagnosis of IgAN and IMN.

Discordance of light chain isotypes between serum and glomerular deposits in proliferative glomerulonephritis with monoclonal IgG deposits: a case report and review of the literature

BackgroundProliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a disease entity with nonorganized granular glomerular deposition with monoclonal proteins of both heavy and light chains. Dysproteinemia was observed in only 30% of the patients with PGNMID. We herein report a case of PGNMID with discrepancy between serum and glomerular deposits.Case presentationThe patient was a 50-year-old man who had been followed at a local clinic due to hypertension, type 2 diabetes, hyperlipidemia, hyperuricemia, fatty liver, and obesity. Proteinuria had been noted five years previously, and he had been referred to a hematology department due to hyperproteinemia, high gamma globulin, and κ Bence-Jones protein (BJP) positivity one year previously. Bone marrow aspiration showed 5% plasma cells, and he was referred to the nephrology department to evaluate persistent proteinuria. He was hypertensive, and his estimated glomerular filtration rate was 54.2 ml/min/1.73 m2. His urinary protein level was 0.84 g/g⋅Cr. Urine and serum immunofixation showed BJP-κ type and IgG-κ type, respectively. Kidney biopsy showed an increase in mesangial cells and matrix without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of IgG and C3 on the capillary wall and weak positivity for C1q. IgG3 was predominant among the IgG subclasses, and intraglomerular κ and λ staining was negative for κ and positive for λ. Direct fast scarlet staining was negative. Electron microscopy showed lumpy deposits without a fibrillar structure in the subepithelial area. Based on the above findings, a diagnosis of membranous nephropathy-type PGNMID was made. Since proteinuria increased gradually after three years of treatment with valsartan (40 mg, daily), oral prednisolone (30 mg, daily) was initiated, which led to decreased proteinuria. The dose of oral prednisolone was gradually tapered to 10 mg per day. At that time, proteinuria was 0.88 g/g⋅Cr. We found 204 cases in 81 articles in the PubMed database, among which 8 showed discrepancy in the heavy and/or light chains between serum and kidney.ConclusionsWe experienced a case of membranous nephropathy-type PGNMID with discrepancy in light chains between serum and kidney that was successfully treated with oral prednisolone.

#5295 SECONDARY MEMBRANOUS NEPHROPATHY WITH IGA DEPOSITS IN A PATIENT WITH PRIMARY CILIARY DYSKINESIA

Abstract Background and Aims Membranous nephropathy and IgA nephropathy are two types of common glomerulonephritis worldwide. There are reports of the coexistence of these glomerulopathies, mostly with mesangial expansion and IgA deposits. Furthermore, primary ciliary dyskinesia is rarely associated to glomerulopathy. Thus, we report a case of a patient with primary ciliary dyskinesia with renal biopsy demonstrating membranous glomerulopathy associated with IgA and IgG deposits exclusively in glomerular basement membrane, without complement deposition. Method Case report. Results A 18 years-old man was referred from the nephropediatric outpatient clinic with subnephrotic hematuria and proteinuria. His medical history included a clinical diagnosis of primary ciliary dyskinesia due to a history of several respiratory infections since birth, asthma, rhinitis and bronchiectasis and a 15 years-old brother with a similar history. He was diagnosed with idiopathic thrombocytopenic purpura at age of one year-old and received prednisone. At 3 years-old he presented with nephrotic syndrome, hematuria and hypertension, and was treated with intravenous methylprednisolone and oral cyclophosphamide for three months. Renal biopsy demonstrated mesangial expansion and thickening of the glomerular basement membrane (GBM), without adequate material for immunofluorescence. Because proteinuria and hematuria persisted, the prednisone dose was increased to 2 mg/kg/day and cyclosporine was started. After 5 years on these medications, persisting with proteinuria, a second biopsy was performed and showed 16 glomeruli, three globally sclerosed and the others with diffuse thickening of the GBM, without other alterations, focal interstitial fibrosis and tubular atrophy and diffuse granular deposits of IgA 1+ and IgG 2+ along the GBM. Cyclosporine and prednisone were discontinued. At age of 18 years-old, he was admitted to adult glomerulonephritis clinic with significant developmental delay (weight 28.6kg and height 1.29m2), no edema and normal arterial blood pressure with RAAS inhibition. Laboratory tests: Hb 8.9 g/dL, serum iron 12 mcg/dL, Creatinine 0.7 mg/dL, albumine 2.3 g/dL. Serologies were negative for syphilis, hepatitis B and C, HIV, ANA and anti-DNA, with normal complement C3, C4 and C1q. Urinalysis revealed proteinuria 1+, hematuria 16.000/mL and proteinuria 1.400 mg/d. CT scan showed symmetrical bronchiectasis in both lungs, with mucoid endobronchial impingement and diffuse bronchial parietal thickening; and chronic post-thrombotic changes with calcified thrombi in the left renal vein, extending into the inferior vena cava. A third renal biopsy was performed showing 38 of 45 (84%) globally sclerosed glomeruli without mesangial matrix changes or capsular adhesions. GBM was thickened with spicules and holes and reactive podocytes. The tubulointerstitial compartment showed moderate atrophy and fibrosis (40-50%). Immunofluorescence microscopy evidenced strong immunoreactivity of IgG 3+/3+, IgA 3+/3+, Kappa 3+/3+ and Lambda 2+/3+, in granular pattern exclusively in GBM, without C3. Electron microscopy showed four sclerosed glomeruli, without deposits. Immunohistochemistry staining for IgG1 2+/3+, and it was negative for PLA2R, NELL-1, THSD7A, Exostosin-1 and 2, IgG 2, IgG3 and IgG4. The patient was maintained with supportive treatment, with RAAS inhibition and SGLT2 inhibitors, without immunosuppression. Conclusion This case highlights the codominance of IgG1 and IgA deposits along the MBG, without proliferation or mesangial deposition and without complement activation, in a patient with membranous nephropathy and primary ciliary dyskinesia, a condition rarely associated with glomerulopathies. Although rare, such renal biopsy findings reinforce the need for a better understanding of the different mechanisms of membranous nephritis, in addition to better understanding and management of treatment in this situation.

#4488 OLD BIOPSY IS ALWAYS GOLD, REVISING MEMBRANOPROLIFERATIVE GN DIAGNOSIS IN A RENAL TRANSPLANT PATIENT

Abstract Background and Aims MPGN resulting from hepatitis C virus (HCV) infection typically shows granular deposition of immunoglobulin M (IgM), C3, and both kappa and lambda light chains. Immunoglobulin G (IgG) may or may not be present, and C1q is typically negative, the same pathology can be found in other viral infections. The recurrence rate post-transplantation is high, with 33% of immune-complex MPGN. Graft loss is even higher 65%, especially among patients with idiopathic MPGN. Treatment of a patient with significant proteinuria can be tricky, as no proven treatment is described yet, but plasmapheresis and induction with cyclophosphamide were described for heavy proteinuria &amp;gt;3.5 g/day. Method 79 year old female patient, known case of live unrelated renal transplantation in December 2013, primary renal disease is unknown. She had a history of equivocal hepatitis C virus antibodies, but Hepatitis C virus RNA was not detected. She is also known to have Type II Diabetes Mellitus and hypertension. The patient had baseline creatinine of 100-120 micromol/L. 24 hr urine protein was 0.8 g/Day but started rising quickly to reach a peak of 9.2 g/g seven months post-transplantation to nephrotic range proteinuria but her serum albumin level was always above 35 g/L. Serum protein electrophoresis showed no M band, a kappa/ Lambda ratio 1.21 within a normal range (0.260-1.65). Anti- nuclear antibody (ANA), P-ANCA, C-ANCA, and Double-stranded DNA all were negative. Complements were within normal range C3 1.39 g/L (0.79 -1.52), C4 0.44 g/L(0.17-0.57)m rheumatoid factor and Anti- citrullinated peptide antibodies were negative. Hepatitis b Virus surface antigen and core antibodies were not reactive, HIV screening was negative. Urine analysis showed RBCs but no RBC casts. Renal biopsy showed mild mesangial expansion and mild l increase in mesangial cells and matrix. Some glomeruli show increased lobulation with increase in mesangial cells and matrix with segmental endocapillary proliferation There is double contour of the glomerular basement membrane with scattered spikes and holes within the basement membrane seen best with silver stain. There is mild increase in the thickness of glomerular basement membrane. There is focal mild lymphocytic infiltration. Tubulitis is not seen in the examined material. One Focal area of mild interstitial fibrosis. Sampled blood vessels are unremarkable. The stain for C4d is negative. Immunofluorescence showed granular capillary wall immunoreactivity to IgM (+2), C4 (+1), C1q (+1), and Lambda light chain (+2). The glomeruli show no immunoreactivity to IgG, IgA, C3, Kappa and fibrin. The glomeruli show (+) staining for albumin. Tubular protein reabsorption droplets showed immunoreactivity for albumin, IgG, IgM, C3, kappa and lambda light chains. Electron microscopy showed many subendothelial, and mesangial electron-dense deposits. The patient was on maintenance immunosuppression medications inform of mycophenolic acid 720 mg, cyclosporine; 250mg BID, and Prednisolone 5 mg daily.Revisiting the new classification of membranoproliferative glomerulonephritis is challenging in this patient, since there is the dominance of IgM deposition by immunofluorescence and C4 but not C3 makes it challenging, the negative monoclonal band in serum electrophoresis and negative autoimmune workup excludes immune complex mediate MPGN, leave idiopathic MPGN a possibility, keeping in mind that hepatitis C virus infection was never confirmed. On the other hand, IF showed IgM with C4 subendothelial and mesangial dense deposits that excludes away the C4 glomerulopathy. Results Whether this is a recurrence of glomerular disease early on post-transplantation or denovo membranoproliferative disease, she responded well to the addition of losartan 100 mg daily, with a reduction of her urinary protein to less than 1 g/g. the patient never received treatment for the hepatitis C virus. Conclusion In our patient, it is difficult to conclude if the cause of MPGN is recurrence or denovo GN, especially with severe proteinuria that responded well to ACEi treatment. The pathological findings can be tricky.

#5430 ANTI-PLA2R ASSOCIATED MEMBRANOUS NEPHROPATHY AND CHRONIC LYMPHOCYTIC LEUKAEMIA, IS THERE A LINK?

Abstract Background and Aims The spectrum of glomerular lesion that occurs in the context of plasma cell dyscrasias (PCD) is wide, including type I and type II membranoproliferative glomerulonephritis (MPGN), focal proliferative GN, membranous nephropathy (MN), minimal change disease and amyloidosis. A clear-cut link between hematological dyscrasias and glomerulopathy is often offered by the finding of paraproteins in the kidney or by kidney leucocytic infiltration and, in these scenarios, malignancy treatment is often found to be also effective towards the glomerulopathy. In the context of PCD in which proliferation of the B-cell clone does not lead to plasma-cell terminal differentiation such as chronic lymphocytic leukemia (LLC) the physiopathological link with glomerulonephritis is not well established and it's hard to determine whether the combination of these two disorders is fortuitous. With regarding to MN, it's now well established that this histopathological pattern must be related to the presence of circulating autoantibodies, where anti-PLA2R auto-antibodies usually been associated with primary MN. To our knowledge association between LLC and anti-PLA2R associated MN has not been described. Case report We report the case of a 76-year-old man who was admitted in February 2022 with anasarca and acute kidney injury. He had recently been evaluated by a hematologist in the context of suspected chronic lymphocytic leukemia (CLL). Laboratory findings, along with typical CLL white blood cell count, showed decreased kidney function from baseline and were compatible with nephrotic syndrome, with proteinuria progressively increasing up to 27 gr/24 h in the following weeks. CLL was confirmed by lymphocyte typing. A total body CT scan showed mediastinal, abdominal and inguinal lymphadenopathies, but no suspected neoplastic lesions. Screening for autoimmunity tested completely negative, as well as infectious screening for common hepatic viruses (HBV, HAV, HCV), EBV, CMV, HIV, Parvovirus B19. Lymph node biopsy showed no aspects of aggressive lymphoproliferative disease and hematological consultation only indicated clinical and laboratory follow-up of LLC, with no further indication to specific therapies. A kidney biopsy was performed showing diffuse thickening of the basement membrane (Fig. 1) with granular deposition of IgG (+++) and C3 (++) along the glomerular capillary walls at immunofluorescence. Electron microscopy revealed subepithelial immune deposits (Fig. 2) with initial incorporation from the glomerular basement membrane (GBM). Anti PLA2R antibodies, found negative at first determination, subsequently tested positive at high titre (ELISA 1356.4 U/ml). A diagnosis of stage two membranous nephropathy was made, and the patient was treated with Rituximab 375 mg/m2 every week for four weeks. Clinical stability was obtained with repeated intravenous administration of diuretics (furosemide 60 mg + canrenone 200 mg) along with albumin. Nevertheless, nephrotic syndrome persisted, and kidney function progressively decreased with serum creatinine up to 2.8 mg/dL. Immunophenotype, which showed reduction but no suppression of CD19+ lymphocytes, was again repeated on November 2022 and showed typical LLC findings (CD 19+, CD 20+, CD 23+, CD 5+) with repopulation of CD19+ lymphocytes. Anti PLA2R antibodies gradually decreased instead, reaching a value of ELISA 1.8 U/ml in November 2022 and persisted negative until present. The patient recovered from nephrotic syndrome in Autumn 2022 and is currently on stage G3B chronic kidney disease with persistent sub-nephrotic proteinuria in supportive treatment. Conclusion Simultaneous diagnosis of primary MN and LLC led us to ask ourselves whether this patient could benefit from LLC-specific chemotherapy, even though there were no signs of aggressive hematological disease and no clear link with the nephropathy. We think that further investigations are required to deeply understand the connection between hematological and renal disorders, in order to identify whether there are two diseases to treat separately or two sides of the same disease to treat as one.