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Anti-glomerular basement membrane (anti-GBM) antibody disease is a rapidly progressive glomerulonephritis characterized by (i) positivity to anti-GBM in serum reacting with a specific antigen present in type IV collagen at both the glomerular and alveolar levels (ii) presence of crescent on light microscopy and positivity to linear deposits of IgG and C3 on immunofluorescence. In the classic variant, the clinic is that of a nephro-pneumological syndrome but there are variants. Rarely, the glomerular damage is pauci-immune. We describe a case of a variant in which there is anti-MBG positivity in serum but negative immunofluorescence and offer a review of the literature and potential treatments.

BACKGROUND: In vitro studies have produced conflicting results about the significance of the JC Polyoma Virus (JCV) in the human cancers.
OBJECTIVE: Our study aims to detect the presence of JCV Large T antigen (LTag) together with viral load quantitation in the prostate tumor samples to assess if JCV harbors risk factor for prostate cancer (PCa).
METHODS: This was a case control-based study. A total of 110 patients participated in this study, including 55 patients with PCa and another 55 patients with benign prostatic hyperplasia (BPH) as cases and controls, respectively. Tissue, blood and urine samples were collected from each participant. Tissues samples were analyzed for the presence of JCV Ltag using a direct immunofluorescence assay (IF). Only positive IF tested samples were subjected to viral quantitation assay. Data were collected and managed using SPSS version 20.
RESULTS: The JCV LTag in the cases group was 23.63% (13/55) which was higher than that of the controls group 5.45% (3/55) with a P. value of .006 and O.R of 5.76. The mean of viral load was significantly higher among cases tissue specimens 20156 ± 5450 copies/ml compared to controls group 6378 ± 2456copies/ml with P-value of .002. The virus was detected in 11/13 (84.6%) urine samples of cases with a mean viral load of 14068 ± 4590 copies/ml compared to 2/3 (66.6%) of controls viral load 2534 ± 1267 copies/ml.
CONCLUSIONS: In conclusion, a higher JCV LTag with more viral load were detected in cases group compared to controls. Our findings support a strong relationship between JCV infection and the probability of developing PCa.

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Immune checkpoint inhibitors (ICIs) became the standard treatment for many different kinds of cancers and can result in a variety of immune-related adverse events (irAEs). IrAEs of kidney are uncommon and consists of different pathology types. Among the different types, membranous nephropathy (MN) is rare and have not been well-described. Since MN can also be associated with malignancies, differential diagnosis in patients receiving ICIs who develop MN can be very difficult. We present the case of a 74-year-old man with metastatic non-small cell lung cancer who developed MN after ICIs therapy. The patient tested positive for thrombospondin type-1 domain-containing 7A antibodies (THSD7A) when diagnosed with MN. Supplementary examinations revealed the predisposing antigen in the primary tumor and present of the antibody after immunotherapy, which corresponded to the patient\'s clinical course of nephropathy. Treatment consisting of systemic glucocorticoids and rituximab resulted in a good clinical response, and the THSD7A antibodies were no longer detected. In this case, we first discuss the potential mechanism of immunotherapy related MN, in which the activation of humoral immunity may play an important role.

Intercalation allows cells to exchange positions in a spatially oriented manner in an array of diverse processes, spanning convergent extension in embryonic gastrulation to the formation of tubular organs. However, given the co-occurrence of cell intercalation and changes in cell shape, it is sometimes difficult to ascertain their respective contribution to morphogenesis. A well-established model to analyse intercalation, particularly in tubular organs, is the Drosophila tracheal system. There, fibroblast growth factor (FGF) signalling at the tip of the dorsal branches generates a \'pulling\' force believed to promote cell elongation and cell intercalation, which account for the final branch extension. Here, we used a variety of experimental conditions to study the contribution of cell elongation and cell intercalation to morphogenesis and analysed their mutual requirements. We provide evidence that cell intercalation does not require cell elongation and vice versa. We also show that the two cell behaviours are controlled by independent but simultaneous mechanisms, and that cell elongation is sufficient to account for full extension of the dorsal branch, while cell intercalation has a specific role in setting the diameter of this structure. Thus, rather than viewing changes in cell shape and cell intercalation as just redundant events that add robustness to a given morphogenetic process, we find that they can also act by contributing to different features of tissue architecture.

Hashimoto\'s encephalopathy is an encephalitis of presumed autoimmune origin characterized by the presence of autoantibodies against thyroid proteins. We present a case of a young patient with pre-existing Hashimoto\'s thyroiditis and progressive cognitive complaints, absence-like episodes, and sporadic bilateral epileptiform frontal and frontotemporal activity. No abnormalities were observed during the neurological examination and on MRI. Antibodies to thyroid peroxidase (TPO) were elevated and remained positive while the symptoms were present. Levothyroxine and methylprednisolone did not ameliorate the complaints. Subsequent treatment with high-dose intravenous immunoglobulins (IVIG) led to improved cognitive functions and to the disappearance of the absence-like-episodes. Patient\'s serum, but not CSF, gave a characteristic IgG-specific hippocampal pattern in rat brain immunohistochemistry; this immunoreactivity was maintained after specific and complete depletion of TPO antibodies. Serum IgG bound to primary neurons in cell culture, likely targeting a yet unidentified neuronal surface antigen. The clinical response to IVIG suggests but does not prove, that the circulating novel autoantibodies may induce the encephalopathy. It would be of interest to investigate more patients with Hashimoto\'s encephalopathy for the presence of neuronal surface autoantibodies, to define their role in the disease and their target antigen(s).

For most of the >2000 CFTR gene variants reported, neither the associated disease liability nor the underlying basic defect are known, and yet these are essential for disease prognosis and CFTR-based therapeutics. Here we aimed to characterize two ultra-rare mutations - 1717-2A > G (c.1585-2A > G) and S955P (p.Ser955Pro) - as case studies for personalized medicine.
Patient-derived rectal biopsies and intestinal organoids from two individuals with each of these mutations and F508del (p.Phe508del) in the other allele were used to assess CFTR function, response to modulators and RNA splicing pattern. In parallel, we used cellular models to further characterize S955P independently of F508del and to assess its response to CFTR modulators.
Results in both rectal biopsies and intestinal organoids from both patients evidence residual CFTR function. Further characterization shows that 1717-2A > G leads to alternative splicing generating <1% normal CFTR mRNA and that S955P affects CFTR gating. Finally, studies in organoids predict that both patients are responders to VX-770 alone and even more to VX-770 combined with VX-809 or VX-661, although to different levels.
This study demonstrates the high potential of personalized medicine through theranostics to extend the label of approved drugs to patients with rare mutations.

Full house nephropathy is defined as the simultaneous detection of IgA, IgG, IgM, C3, and C1q deposits by immunofluorescence, usually indicating lupus nephritis. There are patients with this immunofluorescence pattern, but with negative autoantibody serology, which means they cannot be diagnosed with systemic lupus erythematosus. Patients presenting with full house nephropathy but no other criteria for lupus are diagnosed as having nonlupus full house nephropathy. Here, we describe two cases: A male patient who debuted with rapidly progressive glomerulonephritis and a female patient with nephrotic syndrome. Both had negative autoantibody serology, findings in the renal biopsy of class IV lupus nephritis and afull house immunofluorescence pattern. Histological findings in non-lupus full house nephropathy are similar to those in lupus nephritis and, probably, similar physiopathological bases. However, prospective studies are needed to determine risk factors and the renal prognosis and to make suggestions for specific treatments.
La nefropatía full house se refiere a la detección simultánea de depósitos de IgA, IgG, IgM, C3 y C1q en la inmunofluorescencia, lo que generalmente indica la presencia de nefritis lúpica. Hay pacientes con este patrón de inmunofluorescencia, pero con serología negativa para autoanticuerpos, por lo que no se les puede diagnosticar un lupus eritematoso sistémico. Este tipo de nefropatía, en la que no se presentan otros criterios para lupus, se denomina nefropatía full house no lúpica. En esta presentación, se describen dos casos: un paciente que ingresó con una glomerulonefritis rápidamente progresiva y una paciente con síndrome nefrótico, ambos con serología negativa para autoanticuerpos, hallazgos en la biopsia renal indicativos de nefritis lúpica de clase IV y un patrón full house en la inmunofluorescencia. La nefropatía full house no lúpica tiene rasgos histológicos similares a los de la nefritis lúpica y, probablemente, sus bases fisiopatológicas son parecidas. Sin embargo, se necesitan estudios prospectivos para conocer los factores de riesgo y el pronóstico renal, y poder hacer sugerencias sobre tratamientos específicos.

A 52-year-old woman was diagnosed with chronic myeloid leukemia. Treatment with dasatinib, a second-generation Bcr-Abl tyrosine kinase inhibitor, was initiated, and complete cytogenetic remission was achieved. Two years later, proteinuria occurred, and the urinary protein level increased gradually in the next 3 years. Moreover, the serum creatinine level increased mildly during this period. The urinary protein level reached 2.18 g/gCr; hence, a renal biopsy was conducted. Light microscopy revealed mild proliferation of mesangial cells, and immunofluorescence analysis revealed IgG and C3 depositions in the mesangial area. Electron microscopy revealed electron-dense deposition in the paramesangial area, partial podocyte foot process effacement, and segmental endothelial cell swelling with a slight expansion of the subendothelial space. Dasatinib was discontinued, and within 3 weeks, the proteinuria disappeared, with improvements in her renal function. After switching to bosutinib, a new second-generation of tyrosine kinase inhibitor, the proteinuria remained negative. The rapid cessation of proteinuria following dasatinib discontinuation indicated that proteinuria was induced by the long-term administration of dasatinib. Proteinuria and renal function should be regularly monitored during dasatinib therapy.