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Yousef Ahmed Fouad,1 Abdelrahman Gaber Salman,1 Thanaa Helmy Mohamed,1 Randa Hesham Ali Abdelgawad,1 Samah Ibraheem Hassen2 1Department of Ophthalmology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 2Department of Dermatology, Faculty of Medicine, Ain Shams University, Cairo, EgyptCorrespondence: Yousef Ahmed FouadDepartment of Ophthalmology, Faculty of Medicine, Ain Shams University, Ramses Street, Cairo, EgyptTel +20 1063781237Email yousef.a.fouad@gmail.comBackground: Vitiligo is a common skin condition affecting 0.5– 2% of the population. The exact etiology of the condition is unknown, but the result is autoimmune destruction of melanocytes. The eye is rich in melanocytes, especially in the retinal pigment epithelium and choroid. Little is known about the effect of vitiligo on the choroid of the eye.Methods: We cross-sectionally examined 31 right eyes of 31 vitiligo patients and 32 right eyes of 32 age- and sex-matched controls for signs of vitiligo affection and then measured the subfoveal choroidal thickness (SFCT) using spectral-domain optical coherence tomography.Results: There was a statistically significant difference between SFCT in the cases group and the control group (Mean ± SD: 251.9 ± 42.0 μm and 296.8 ± 46.4 μm, respectively, p = 0.0002). The thickness correlated negatively with age (r = − 0.5) but did not correlate significantly with disease severity or duration (r = − 0.201, − 0.1781, p = 0.2783, 0.3381, respectively). Additional examination findings included iris and fundus hypopigmented spots, and peripapillary atrophy.Conclusion: SFCT is reduced among patients with vitiligo. The clinical implications of such a finding should be studied further, and eye screening programs should be considered.Keywords: vitiligo, OCT, optical coherence tomography, choroidal thickness

Background: Psoriasis is a systemic inflammatory disorder. It is associated with increased risk of developing other chronic health diseases such cardiovascular disorders. Fetuin A is a glycoprotein that is present in blood serum. It may prevent vascular calcification by forming calciprotien particles; which are formed from their attachment with phosphate and calcium complexes., Aim: The aim of this study was to measure serum Fetuin A in Psoriatic patients and correlate its level with cardiac events and risks in these patients using CT calcium (Ca) scoring., Patients and Methods: 24 psoriatic patients (healthy without apparent cardiac risks to detect subclinical events if present) and 24 age and sex matched controls were tested for serum Fetuin A and underwent coronary calcium scoring by multidetector computed tomography (CT) scan. Psoriasis area and severity index (PASI) score for each patient was measured and was correlated with serum Fetuin A and CT calcium (Ca) scoring. Serum Fetuin A was compared between cases and controls and was correlated with coronary calcium score., Results: There was highly statistically significant decrease in serum Fetuin A level in psoriatic group compared to control group ( P -value < .001). There was highly statistically significant negative correlation between calcium score and the level of serum Fetuin A ( P -value < .001). No statistically significant correlation was found between the serum level of Fetuin A and the psoriasis severity., Conclusion: Serum Fetuin A is a simple, easy diagnostic tool to evaluate subclinical atherosclerosis in psoriatic patients., (© The Author(s) 2023.)

Background: Nail affection is seen in up to 50 % of patients with skin psoriasis, although up to 5% of nail psoriatic patients do not complain of skin affection. Various treatment options are emerging for nail psoriasis such as intense pulsed light Tawfik, 2014). Methylene-blue (M.B) is a phenothiazine dye which is suggested to mediate cell cyto-toxicity by the generation of hydroxyl-radicals which change the intra-cellular calcium homeo-static mechanisms (Lee and Wurster, 1995)., Objectives: Evaluation and comparing the efficacy of I.P.L. and methylene-blue assisted photo-dynamic therapy for treating psoriatic nails., Patients and Methods: 20 patients with mild to moderate psoriasis with nail involvement. Sessions were performed once every 2 weeks on all the affected nails for a maximum of 3 months (6 sessions). Nail Psoriasis Severity Index (N.A.P.S.I.) score and photo-documentation were done for all the patients to assess the nail status at the first visit, after two, six sessions and three months after finishing the six session (0 m., 1 m., 3 m. and 6 m.). Nails of the right hand were treated with methylene-blue mediated photo-dynamic therapy using the Intense Pulsed Light (IPL) as the light source, while the left hand received conventional IPL (430-1200 nm) alone., Results: The present study showed that both treatments were effective on nail psoriasis, but MB-PDT was more effective in nail-bed lesions. There was no significant difference regarding patient satisfaction., Conclusion: Both Intense Pulsed Light and methylene-blue assisted photo-dynamic therapy were safe, nearly pain-free, easy to use, and effective for treating nail psoriasis. MB-PDT is a new promising strategy for the treatment of nail psoriasis., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, antigenic targets of disease are unknown for over 10% of patients with MN and over half of those with membranous lupus nephritis (MLN). Here, we identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies through mass spectrometry of immune complexes recovered from biopsy tissue of patients with MN. Patients with MN negative for these four antigens were identified from Arkana Laboratories case archives. Protein G immunoprecipitation recovered immune complexes from frozen biopsy tissue from 142 quadruple-negative cases and 278 cases of known antigen type, followed by interrogation by mass spectrometry. Potential putative antigens were confirmed through paraffin immunofluorescence and co-localization with IgG within immune deposits. Consecutive series of 165 cases of PLA2R-negative MN and 142 MLN biopsies were screened to determine the frequency for each potential antigen. Seven putative antigens were discovered within immune complexes from biopsies of patients with MN including FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1, and VASN. Peptides from these proteins were not enriched in the 278 cases of known antigen type. Between three to 30 unique peptides were detected for each new target. Frequencies of each biomarker, determined by staining consecutive case series, ranged from under 1 to 4.9%. NPR3 and CD206 were only positive in index cases. All cases showed co-localization of IgG within the immune deposits. Thus, seven putative antigens were newly identified in MN and MLN. Due to the number of antigens identified, it is becoming impractical to type PLA2R-negative MN or MLN cases through immunostaining alone. A multiplex approach is needed for subtyping of these diseases., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. It has been shown in phospholipase A2 receptor positive membranous nephropathy that known antibodies can be detected within sera, determination of the target autoantigen can have diagnostic significance, inform prognosis, and enable non-invasive monitoring of disease activity. Here we utilized mass spectrometry for antigen discovery in laser captured microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue protein G immunoprecipitation studies to interrogate immune complexes from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in some cases of membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1 association was 6.6% of cases of membranous lupus nephritis and in 2.0% of primary membranous nephropathy cases. NCAM1 was found to colocalize with IgG within glomerular immune deposits by confocal microscopy. Additionally, serum from patients with NCAM1-associated membranous nephropathy showed reactivity to NCAM1 recombinant protein on Western blotting and by indirect immunofluorescence assay, demonstrating the presence of circulating antibodies. Thus, we propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Membranous lupus nephritis (MLN) comprises 10%-15% of lupus nephritis and increases morbidity and mortality of patients with SLE through complications of nephrotic syndrome and chronic kidney failure. Identification of the target antigens in MLN may enable noninvasive monitoring of disease activity, inform treatment decisions, and aid in prognostication, as is now possible for idiopathic MN caused by antibodies against the phospholipase A2 receptor. Here, we show evidence for type III TGF- β receptor (TGFBR3) as a novel biomarker expressed in a subset of patients with MLN., Methods: Mass spectrometry was used for protein discovery through enrichment of glomerular proteins by laser capture microdissection and through elution of immune complexes within MLN biopsy specimens. Colocalization with IgG within glomerular immune deposits from patients and disease controls was evaluated by confocal microscopy. Immunostaining of consecutive case series was used to determine the overall frequency in MN and MLN., Results: TGFBR3 was found to be enriched in glomeruli and coimmunoprecipitated with IgG within a subset of MLN biopsy specimens by mass spectrometry. Staining of consecutive MN cases without clinical evidence of SLE did not show TGFBR3 expression (zero of 104), but showed a 6% prevalence in MLN (11 of 199 cases). TGFBR3 colocalized with IgG along the glomerular basement membranes in TGFBR3-associated MN, but not in controls., Conclusions: Positive staining for TGFBR3 within glomerular immune deposits represents a distinct form of MN, substantially enriched in MLN. A diagnosis of TGFBR3-associated MN can alert the clinician to search for an underlying autoimmune disease., Competing Interests: J. M. Arthur reports serving as a scientific advisor for, or member of, Kidney360; and receiving honoraria from Travere Pharmaceuticals. L. H. Beck reports serving on the advisory boards of Alexion, Genentech, Ionis, and Visterra; serving on the editorial boards of Kidney International Reports and Kidney Medicine; receiving research funding from Pfizer and Sanofi-Genzyme; receiving honoraria from UpToDate, Inc.; and being a coinventor on, and receive royalties related to, the US patent “Diagnostics for Membranous Nephropathy.” D. J. Kenan reports having patents and inventions with EMD Millipore. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Patients with membranous nephropathy have an increased risk of malignancy compared to the general population, but the target antigen for malignancy-associated membranous nephropathy is unknown. To explore this, we utilized mass spectrometry for antigen discovery in malignancy-associated membranous nephropathy examining immune complexes eluted from frozen kidney biopsy tissue using protein G bead immunoglobulin capture. Antigen discovery was performed comparing cases of membranous nephropathy of unknown and known type. Mass spectrophotometric analysis revealed that nerve epidermal growth factor-like 1 (NELL1) immune complexes were uniquely present within the biopsy tissue in membranous nephropathy. Additional NELL1-positive cases were subsequently identified by immunofluorescence. In a consecutive series, 3.8% of PLA2R- and THSD7A-negative cases were NELL1-positive. These NELL1-positive cases had segmental to incomplete IgG capillary loop staining (93.4%) and dominant or co-dominant IgG1-subclass staining (95.5%). The mean age of patients with NELL1-positive membranous nephropathy was 66.8 years, with a slight male predominance (58.2%) and 33% had concurrent malignancy. Compared with PLA2R- and THSD7A-positive cases of membranous nephropathy, there was a greater proportion of cases with malignancies in the NELL1-associated group. Thus, NELL1-associated membranous nephropathy has a unique histopathology characterized by incomplete capillary loop staining, IgG1-predominance, and is more often associated with malignancy than other known types of membranous nephropathy., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency syndromes, affecting one in 25,000-50,000 people. Renal insufficiency occurs in approximately 2% of patients with CVID. To date, there are no case series of renal biopsies from patients with CVID, making it difficult to determine whether individual cases of renal disease in CVID represent sporadic events or are related to the underlying pathophysiology. We performed a retrospective analysis of renal biopsy specimens in our database from patients with a clinical history of CVID ( n =22 patients, 27 biopsies)., Methods: Light, immunofluorescence, and electron microscopy were reviewed. IgG subclasses, PLA2R immunohistochemistry, and THSD7A, EXT1, and NELL1 immunofluorescence were performed on all membranous glomerulopathy cases. CD3, CD4, CD8, and CD20 immunohistochemistry was performed on cases of tubulointerstitial nephritis., Results: AKI and proteinuria were the leading indications for renal biopsy in patients with CVID. Immune-complex glomerulopathy was present in 12 of 22 (54.5%) cases, including nine cases with membranous glomerulopathy, one case with a C3 glomerulopathy, and one case with membranoproliferative GN with IgG3 κ deposits. All membranous glomerulopathy cases were PLA2R, THSD7A, EXT1, and NELL1 negative. The second most common renal biopsy diagnosis was chronic tubulointerstitial nephritis, affecting 33% of patients. All tubulointerstitial nephritis cases showed tubulitis and a lymphocytic infiltrate with >90% CD3 + T cells. Other renal biopsy diagnoses within our cohort included acute tubular injury ( n =1), amyloid light-chain amyloidosis ( n =1), diabetic glomerulosclerosis ( n =1), thin basement membranes ( n =1), pauci-immune GN ( n =1), and arterionephrosclerosis ( n =1)., Conclusions: Membranous glomerulopathy and tubulointerstitial nephritis were the predominant pathologic findings in patients with CVID. Membranous glomerulopathy cases in patients with CVID were IgG1 subclass dominant and showed mesangial immune deposits. Four of the membranous glomerulopathy cases had associated proliferation, with mesangial and/or endocapillary hypercellularity, with or without crescent formation. CVID should be considered as a potential cause when membranous glomerulopathy or chronic tubulointerstitial nephritis is seen in a young patient with a history of recurrent infections., Competing Interests: All authors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)