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نفذت الزراعة خلال الموسم الزراعي الأول في عام 2021في محطة البحوث العلمية – منطقة ستخيرس واتبع في تصميمها العشوائية الكاملة وشملت التجربة أربع معاملات من مولاس الشوندر السكري(B0=0-B1=75- B3=225-B2=150 ل/هكتار). أظهرت النتائج انخفاض الكثافة الظاهرية للتربة مع إضافة المولاس في الطبقة السطحية من 20-0سم بمقدار 0.13غ/سم3عند مستوى إضافة 225ل/هكتار, أما في العمق من 40-20سم فكان الانخفاض بمقدار 0.23غ/سم3 مقارنة بالشاهد. وتبين أن مساحة المسطح الورقي تتراوح بين 3450 cm2إلى 11606cm2للنبات الواحد بعد ثلاثة أشهر من الزراعة وكانت أفضل مساحة عند مستوى إضافة 225ل/هكتار من المولاس. أعطت أفضل إنتاجية للنبات الواحد عند مستوى إضافة 225ل/هكتار من المولاس حيث بلغت 3229 كغ/دونم .

أجريت هذه الدراسة خلال الموسم الربيعي لعام 2021 في قرية بسيسين التي تبعد 3km عن مدينة جبلة التابعة لمحافظة اللاذقية بهدف دراسة تأثير التغذية الورقية بمركب اليوريا ومعلق الخميرة في نمو وإنتاجية نبات الخيار ضمن البيت البلاستيكي. استخدم في التجربة 5 معاملات وهي مركب اليوريا بتركيز(200-300mg/l) ومعلق الخميرة بتركيز(4-6g/l) إضافة إلى معاملة الشاهد في أربع مكررات لكل معاملة. فيما يخص مؤشرات النمو، سجلت اليوريا 300 mg/lأعلى ارتفاع للنبات وقدره ( 232.1(cm وأكبر عدد أوراق ( 45.93 ورقة ) وأكبر عدد من الفروع ( 10.400 فرع) وبالتالي أعطت أكبر مسطح ورقي وبلغ (18217 cm2) كما بينت النتائج أن الرش الورقي باليوريا 300 mg/l أعطى أكبر عدد من الثمار (81.94 ثمرة) وأكبر متوسط وزن للثمرة (106.90g) ونتج عنه أعلى إنتاج (30.58kg/m2).

نفذ البحث في قرية الشراشير التي تبعد 3 كم شمال مدينة جبلة في شهر أذار للموسم الزراعي 2020-2021 -هدف البحث إلى تحسين النمو الخضري والثمري للفاصولياء من القرون الخضراء باستخدام الرش الورقي بمستخلص الطحالب البحرية وكبريتات الزنك والحديد شملت الدراسة ست معاملات من الرش الورقية بالإضافة إلى معاملة الشاهد المرشوشة نباتاته بالماء فقط واتبع في تنفيذ البحث تصميم القطاعات العشوائية الكاملة بأربع مكررات لكل معاملة وبواقع 15 نبات في كل مكرر. -أظهرت الدراسة تفوق النباتات المرشوشة بمستخلص الطحالب البحرية وكبريتات الزنك والحديد معنويا على النباتات الغير مرشوشة وذلك في كافة مؤشرات النمو الخضري والزهري وكمية الإنتاج كما بينت النتائج أن النباتات المرشوشة بمستخلص الطحالب البحرية وكبريتات الزنك قد تفوقت معنويا على بقية المعاملات حيث سجلت أعلى القيم في طول النبات 296 )سم /نبات (وعدد الأوراق 32) ورقة /نبات (ومساحة المسطح الورقي 10614) سم (2 وعدد الأزهار 178) زهرة ( وعدد القرون 84.3) قرن( والأنتاج الكلي من القرون الخضراء 4.11) كغ/م ( 2

نفذت التجربة في قرية بيت المرج التابعة لمنطقة القدموس ، وذلك خلال عام 2019 ، في تربة طينية زرعت بنبات الفليفلة ، حيث تم دراسة سبع معاملات تسميدية من الأسمدة الآزوتية و الفوسفاتية و البوتاسية ، بوجود وغياب السماد العضوي ، وتحت الظروف الحقلية المفتوحة . أظهرت النتائج تفوق المعاملتين T1 ، T7 معنوياً على جميع المعاملات المدروسة في توفير متطلبات نبات الفلفل من العناصر الغذائية ، ,وبالمقابل فقد أدت زيادة كمية السماد الآزوتي المضاف في المعاملة T7 إلى زيادة تشجيع النمو الخضري لنبات الفليفلة والتأخر في الدخول في مرحلة الإزهار مقارنةً بباقي المعاملات المدروسة ، في حين انخفض محتوى التربة من العناصر الغذائية المتاحة لنبات الفليفلة في المعاملة T3 لغياب التسميد العضوي . وظهر بالنتيجة أن المعاملة T1 في ظروف التربة الطينية كانت من أفضل المعاملات المدروسة حيث ساهمت في رفع خصوبة التربة ، مع الاستخدام الأمثل للأسمدة ، ودون حدوث تلوث للبيئة أو ملوحة للتربة .

أجري البحث في قرية برنه التابعة لمحافظة اللاذقية في عروة ربيعية لعام 2019، بهدف دراسة تأثير رش نباتات البطاطا الصنف سبونتا بمعلق الخميرة والبورون في بعض مؤشرات النمو والإنتاجية، حيث شملت التجربة تسع معاملات : (رش النباتات بالخميرة بتركيزين 4 و6 غ/ل والرش بالبورون بتركيزين ( 400 و 600) PPM والرش المختلط من الخميرة والبورون بالتراكيز السابقة بالإضافة الى معاملة الشاهد الرش بالماء المقطر) على مؤشرات النمو الخضري والإنتاجية، وفق تصميم القطاعات العشوائية الكاملة بثلاثة مكررات لكل معاملة وبمعدل عشر نباتات لكل مكرر . أظهرت النتائج التأثير الإيجابي لرش النباتات بالخميرة والبورون في زيادة مساحة المسطح الورقي للنبات ودليله حيث بلغت أعلى مساحة للمسطح الورقي ودليله في المعاملة T9(رش النباتات بمحلول الخميرة بتركيز 6 غ/ل وبحمض البوريك بتركيز 600 PPM حيث تفوقت هذه المعاملة معنوياً على بقية المعاملات المدروسة بقيمة 13455سم2/نبات وتفوقت أيضاً في ارتفاع النباتات حيث بلغ 80 سم، وكذلك اعطت أعلى إنتاجية بلغت 5.17 كغ/م2 ، و أعلى القيم لعدد الدرنات 10.80 درنة/نبات ، بينما تفوقت المعاملة T5 معنوياً على بقية المعاملات في متوسط وزن الدرنة بلغ 133.25 غ .

نفذ البحث في عروة ربيعية في قرية صرنا- محافظة اللاذقية في الموسم الزراعي لعام2019، بهدف دراسة تأثير معاملة نباتات البطاطا الصنف بانيلا بحمض الجبرليك GA3 منفردا أو مع مركب فوسفات البوتاسيوم في بعض مؤشرات النمو والانتاجية، استخدم في تنفيذ البحث تصميم القطاعات العشوائيه الكاملة، وشملت الدراسة ست معاملات وهي الرش بحمض الجبرليكGA3 بتركيزين ( 50 ، 100 ) ppm، والرش بفوسفات البوتاسيوم بتركيز 1.5 غ/ل، والرش بحمض الجبرليك بتركيز 100 ppm مع فوسفات البوتاسيوم بتركيز 1.5غ/ل، والرش بحمض الجبرليك بتركيز 50 ppm +فوسفات البوتاسيوم بتركيز 1.5غ/ل بالإضافة للشاهد الذي تم رش النباتات فيه بالماء المقطر. أظهرت النتائج أن لمعاملة نباتات البطاطا بحمض الجبرليك ومركب فوسفات البوتاسيوم تأثير ايجابي في الصفات المورفولوجية ومؤشرات الإنتاج المدروسة وأن معاملة النباتات بحمض الجبريك بتركيز 100 ppm مع مركب فوسفات البوتاسيوم بتركيز 1.5غ/ل تفوقت معنوياً على جميع المعاملات المدروسة من حيث مساحة المسطح الورقي (17384 سم2/نبات)، ودليله (8.278) ، ارتفاع النبات (55 سم)، إنتاج النبات (1817غ/نبات)، إنتاجية وحدة المساحة (8.65 كغ/م2)، عدد الدرنات (15.41 درنة/نبات)، ومتوسط وزن الدرنة (118غ/درنة).

يهدف البحث الى دراسة اتجاه الامطار في العراق خلال السنوات 1941 ولغاية 2017 وعلى شكل بيانات موسمية تبدأ من شهر ايلول وحتى شهر مايس والمتضمنة (76) موسماً، واختيرت عشرة محطات دراسية موزعة مكانياً في عموم العراق، اما العمل الاحصائي في هذا البحث تم على اساس استخراج قيم معادلة الاتجاه لمجموع التساقط المطري خلال الموسم المطير، ومن ثم تحديد مقدار التغير في الاتجاه خلال السلسلة الزمنية لتحديد المستقبل المائي للعراق بالرغم من ان العراق يعتمد في تغذية مياه نهري دجلة والفرات على دول المنبع لكن يبقى التساقط المطري هو الاساس في تغذية المنابع والانهار اضافة الى استغلال كميات الامطار المتساقطة والناتج عنها حدوث سيول في الحصاد المائي لما تعد هذه الكميات المائية من داعم مهم لمياه الانهار.

نفذ البحث خلال الموسم الزراعي الربيعي 2020 ضمن حقل زراعي في قرية الشير لدراسة تأثير بعض مستخلصات الأعشاب البحرية في النمو الخضري وإثمار الخيار. استخدم في الزراعة هجين الخيار برنس ونوعين من مستخلصات الأعشاب البحرية GOFAR SEAWEED,SPRINT ALGA وتضمنت الدراسة 5)) معاملات هي(نباتات معاملة الشاهد مرشوشة بالماء، نباتات مرشوشة بمستخلص GOFAR SEAWEED بتركيز0.5غ/ل وَ 1غ/ل ، نباتات مرشوشة بمستخلص SPRINT ALGA بتركيز(1مل/ل وَ2مل/ل)) و4)) مكررات لكل معاملة وفق تصميم القطاعات العشوائية الكاملة. أظهرت النتائج : أن الرش الورقي بمستخلصات الأعشاب البحرية قد حقق زيادة في طول الساق وعدد الفروع ومساحة المسطح الورقي وبفروق معنوية بالمقارنة مع الشاهد. وتفوقت معاملات الرش الورقي بمستخلصات الاعشاب البحرية أيضاً في عدد الأزهار المؤنثة والثمار المتشكلة على النبات ، حيث أعطت معاملة الرش الورقي بالمستخلص GOFAR SEAWEED تركيز1)غ/ل) أعلى عدد من الأزهار المؤنثة بلغ 82)) زهرة/نبات وأكبر عدد من الثمار بلغ (37) ثمرة/نبات. كما أعطى المستخلص GOFAR SEAWEED بتركيز(1غ/ل) والمستخلص SPRINT ALGAبتركيز2) مل/ل) أكبر إنتاج في وحدة المساحة بلغ(4625 غ/م2) و (4375 غ/م2) على التوالي .

أجريت الدراسة في منطقة سقوبين شمال /اللاذقية/ في الموسم الربيعي لعام 2019 بهدف دراسة تأثير الكثافة النباتية في نمو وإنتاجية بعض هجن الكوسا Cucurbita pepo L.، شملت التجربة تقييم ثلاث هجن من الكوسا، وهي (الهجين الفرنسي Précoce Maraîchère، الهجين مرام F1، الهجين زينب F1) زرعت في ست كثافات زراعية (2.7، 2.4، 2، 1.8، 1.6، 1.4) نبات/م2 لدراسة مؤشرات النمو الخضري والثمري والإنتاجية. وفق تصميم القطاعات العشوائية الكاملة بأربعة مكررات لكل معاملة وبمعدل عشر نباتات لكل مكرر. أظهرت النتائج أن نباتات الهجين زينب قد تفوقت بفروق معنوية على الهجينين الآخرين في كافة المعاملات المدروسة وأعطت المعاملة بكثافة نباتية (1.4) نبات/ م2 أعلى عدد من الأوراق بلغ (26) ورقة/نبات في حين كان عدد الأوراق لنفس المعاملة في الهجين مرام (24) ورقة/نبات وفي الهجين الفرنسي (22) ورقة/نبات. وكذلك تفوق الهجين زينب بفروق معنوية على الهجين مرام والهجين بريكوس مارشيير بمساحة المسطح الورقي في كافة المعاملات المدروسة للكثافات النباتية، وقد أعطت المعاملة ذات الكثافة النباتية (1.4) نبات/م2 أكبر مسطح ورقي بلغ (35636) سم2/نبات، في حين أعطت المعاملة ذات الكثافة النباتية (2.7) نبات/م2 أقل مسطح ورقي لنفس الهجين بلغ (21367) سم2/نبات وفي الهجين الفرنسي أقل مسطح ورقي بلغ (15654) سم2/نبات عند الكثافة النباتية (2.7) نبات/م2، كما وجد أن النسبة الجنسية كانت مرتفعة للهجن الثلاث في الكثافات النباتية المرتفعة وتنخفض إلى أدنى نسبة في الكثافات النباتية المنخفضة وقد وصلت إلى (30.55) % للهجين مرام و (28.37) % للهجين زينب و(28.89) للهجين بريكوس عند الزراعة بكثافة نباتية (1.4) نبات/م2. وأعطت المعاملة ذات الكثافة النباتية المنخفضة (1.4) نبات/م2 أعلى معدل في الإنتاج المبكر لكافة المعاملات المدروسة.

نفذ البحث في الموسم الزراعي (2018- 2019) في قرية حميميم – جبلة بهدف دراسة تأثير السماد العضوي في نمو وإنتاج نبات الباذنجان في الزراعة الحقلية المكشوفة. استخدم في الزراعة هجين "برشلونة " وتضمنت الدراسة 5 معاملات في 4 مكررات لكل معاملة وفق تصميم القطاعات العشوائية الكاملة. أظهرت النتائج أن معاملات التسميد العضوي حققت زيادة بفروق معنوية في النمو الخضري بالمقارنة مع الشاهد غير المسمد عضوياً، حيث أعطت معاملة التسميد العضوي بـ(500)غ/م2 سماد عضوي أعلى قيمة للمسطح الورقي بلغ (8082) سم2)، و أعلى عدد من الازهار بلغ (56.99) زهرة/نبات. كما أعطت أكبر عدد من الثمار العاقدة بلغ 22.24)) ثمرة/نبات.

C3 glomerulonephritis (C3GN) is a recently described disorder that typically results from abnormalities in the alternative pathway (AP) of complement. Here, we describe the clinical features, kidney biopsy findings, AP abnormalities, glomerular proteomic profile, and follow-up in 12 cases of C3GN. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients with native kidney disease. In two patients, C3GN recurred within 1 year of transplantation and resulted in a decline in allograft function. Kidney biopsy mainly showed a membranoproliferative pattern, although both mesangial proliferative and diffuse endocapillary proliferative glomerulonephritis were noted. AP abnormalities were heterogeneous, both acquired and genetic. The most common acquired abnormality was the presence of C3 nephritic factors, while the most common genetic finding was the presence of H402 and V62 alleles of Factor H. In addition to these risk factors, other abnormalities included Factor H autoantibodies and mutations in CFH, CFI, and CFHR genes. Laser dissection and mass spectrometry of glomeruli from patients with C3GN showed accumulation of AP and terminal complement complex proteins. Thus, C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) results from accumulation of antigen-antibody immune complexes along the subepithelial region of the glomerular basement membranes. Over the last years, 13 target antigens have been discovered and include PLA2R, THSD7A, EXT1 and EXT2, NELL1, SEMA3B, NCAM1, CNTN1, HTRA1, FAT1, PCDH7, NTNG1, PCSK6 and NDNF, accounting for 80-90% of MN antigens. MN associated with many of these antigens have distinctive clinicopathologic findings. It is important to accurately identify the antigen in MN. Immunohistochemical (IHC) and/or immunofluorescence (IF) methods are currently used to detect PLA2R, THSD7A, NELL1, SEMA3B and EXT1/EXT2. However, for the remaining antigens, IHC/IF methods do not exist and are not practical for detection. Here, we developed laser microdissection-based mass spectrometry methodology (LMD/MS) as a one-stop clinical test for the detection of MN antigens using paraffin-embedded kidney biopsy tissue. The LMD/MS test was validated in two steps. LMD/MS was used to detect the antigen in 75 cases of MN with known antigens and correctly identified the antigen in all these cases. Next, LMD/MS was used to identify the antigen in 61 MN cases where the antigen was unknown and identified one of the known antigens in 40 of 61 cases including many of the less common antigens. This lower-than-expected detection rate is explained by intentional enrichment of the cohort with PLA2R-negative MN. Overall, PLA2R was identified in 16.4%, one of the other antigens detected in 49.1%, and in the remaining 34.5% of cases, none of the above antigens was detected. Thus, LMD/MS is an extremely useful and reliable method for the detection of known MN antigens and possibly indicating an unknown MN antigen for eventual discovery., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Amyloidosis is a protein folding disease that causes organ injuries and even death. In humans, 42 proteins are now known to cause amyloidosis. Some proteins become amyloidogenic as a result of a pathogenic variant as seen in hereditary amyloidoses. In acquired forms of amyloidosis, the proteins form amyloid in their wild-type state. Four types (serum amyloid A, transthyretin, apolipoprotein A-IV, and β 2 -macroglobulin) of amyloid can occur either as acquired or as a mutant. Iatrogenic amyloid from injected protein medications have also been reported and AIL1RAP (anakinra) has been recently found to involve the kidney. Finally, the mechanism of how leukocyte cell-derived chemotaxin 2 (ALECT2) forms amyloid remains unknown. This article reviews the amyloids that involve the kidney and how they are typed., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Salivary gland amyloidosis is an uncommon diagnosis. Most studies have focused on minor salivary gland biopsies as a surrogate site for diagnosing systemic amyloidosis, while only few studies have investigated major salivary gland amyloidosis. We retrospectively identified 57 major and minor salivary gland amyloidosis cases typed using a proteomics-based method between 2010 and 2022. Frequency of amyloid types, clinicopathologic features, and distribution patterns of amyloid deposits were assessed. The indication for salivary gland biopsy/resection (known in 34 cases) included suspected amyloidosis (N = 14; 41.2%), lesion/mass (N = 12; 35.3%), swelling/enlargement (N = 5; 14.7%), and rule out Sjogren syndrome (N = 3; 8.8%). Concurrent pathology was reported in 16 cases, and included chronic sialadenitis (N = 11), extranodal marginal zone lymphoma (N = 3), plasma cell neoplasm (N = 1), and pleomorphic adenoma (N = 1). We identified 3 types of amyloidosis: immunoglobulin light chain/AL (N = 47; 82.5%); immunoglobulin heavy chain/AH (N = 1; 1.8%), and transthyretin/ATTR (N = 9; 15.8%). The patterns of amyloid deposits (assessed in 35 cases) included: 1) Perivascular and/or periductal distribution (N = 18; 51.4%); 2) Mass formation (N = 9; 25.7%); 3) Stromal micronodule formation (N = 7; 20.0%); and 4) Diffuse interstitial involvement (N = 1; 2.9%). We also identified one case of AL amyloidosis localized to the major salivary gland, where only 6 other cases with adequate staging workup to exclude systemic amyloidosis were previously reported. In conclusion, salivary gland amyloidosis is an uncommon diagnosis but may be underrecognized due to low index of suspicion. Most cases of salivary gland amyloidosis are AL type, but a minority are ATTR. Therefore, proteomics-based typing remains essential for treatment and prognosis., Competing Interests: Declaration of competing interest April Chiu is a consultant with AstraZeneca. None for all other authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: VEXAS syndrome is an autoinflammatory disease caused by somatic mutation of UBA1 and affects multiple organ systems. Involvement of the kidneys is not well characterized. We aimed to investigate the incidence, risk factors and histopathologic features of acute kidney injury (AKI) in VEXAS syndrome., Methods: Patients with genetically confirmed UBA1 mutation consistent with VEXAS were included. Charts were manually reviewed. Cox regression analysis was used to identify variables associated with time-to-first acute kidney injury (AKI) event. For patients with a kidney biopsy, histopathologic findings were reviewed., Results: Eighty-one patients were included, all white men, with a mean age of 66.3±8.6 years. Median (IQR) follow up was 3.5 (2.1-5.2) years during which 20 (25%) developed AKI and 22% died. AKI relapsed in 90% of cases for a median of 6 times during the follow up period. Cumulative incidence estimates (95% CI) for AKI at 1, 3 and 5 years were 6.2% (0.80-11.3%), 16.7% (7.5-25.0%) and 27.9% (14.9-38.9%), respectively. Age and baseline C-reactive protein were significantly associated with time-to-first AKI event. Six patients underwent a kidney biopsy. Findings included, plasma cell-rich interstitial nephritis (n = 3), neutrophilic-rich interstitial inflammation (n = 1), leukocytoclastic peritubular capillaritis (n = 1), and acute tubular injury (n = 1). AKI responded well to treatment with glucocorticoids but had relapse upon tapering., Conclusion: AKI is an underrecognized feature of VEXAS occurring in 25% of patients in this cohort. Age at diagnosis and CRP were associated with time to first AKI event during follow up. Plasma cell-rich interstitial nephritis was the most common histopathologic finding., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Monoclonal Ig crystalline nephropathies are rare lesions resulting from precipitation of monoclonal Igs in the kidney as crystalline inclusions. They can be categorized into lesions with predominant intracellular crystals (light chain [LC] proximal tubulopathy, LC crystal-storing histiocytosis, and LC crystalline podocytopathy) and lesions with predominant extracellular crystals (crystalglobulin-induced nephropathy and crystalline variant of LC cast nephropathy). The majority of these lesions are associated with low tumor burden lymphoproliferative disorders, with the exception of crystalline variant of LC cast nephropathy. Extrarenal involvement (e.g., skin and cornea) is frequent. Kidney biopsy is the cornerstone for diagnosis, which often requires electron microscopy and antigen retrieval. A thorough hematologic workup and evaluation of extrarenal involvement is mandatory for management. Treatment of these lesions is with clone-directed therapy, with the goal of achieving hematologic very good partial response or complete response, which preserves or improves kidney function. In vitro and in vivo studies, animal models, and novel sequencing techniques have been invaluable tools to understand the pathogenesis of LC proximal tubulopathy and can be used to increase our limited knowledge of the pathogenesis of the other monoclonal Ig crystalline nephropathies. This review provides an update on the pathology, renal and hematologic characteristics, extrarenal manifestations, prognosis, treatment, and pathogenesis of monoclonal Ig crystalline nephropathies., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: There is an unmet need to understand the mechanisms by which amyloid deposition drives alterations in the kidney. We leveraged renal biopsies from amyloid light-chain (AL) amyloidosis participants of the Renal AL Amyloid Involvement and NEOD00 (RAIN) trial (NCT03168906) to perform transcriptional profiling and to employ a novel histologic scoring tool. Our objective was to utilize a transcriptome-driven approach to identify AL molecular signatures that may be prognostic., Methods: Clinical data were correlated to histologic and molecular findings. A composite scarring injury and amyloid score (AS) were assigned to each biopsy. Glomerular and tubulointerstitial (TI) compartments were microdissected and sequenced separately. Expression data were compared to healthy living donors and focal segmental glomerulosclerosis (FSGS) profiles. Differentially expressed genes were determined., Results: Cluster analysis revealed 2 distinct patient clusters (G1 and G2) based on gene expression. The AS was higher in the TI compartment (6.5 vs. 4.5; P  = 0.0290) of G2. Glomeruli showed activation of fibrotic pathways and increased canonical signaling of LPS/IL-1. TNF activation was noted in TI. Enriched ingenuity canonical pathways included "coagulation system," "GADD45 signaling," and "Wnt/Ca+ pathway," among others. For AL versus living donors, ingenuity pathway analysis identified enrichment in PI3K/Akt signaling. Gene regulators of cellular proliferation were enriched in the amyloid group., Conclusion: Despite the small sample size, we identified 2 distinct groups of patients with AL based on molecular signatures. Detailed studies of a larger cohort encompassing omics technologies at a single cell resolution will further help to identify the response of individual kidney cell types to amyloid deposits, potentially leading to the development of novel therapeutic targets., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Monoclonal immunoglobulin (MIg) crystalline nephropathies are rare lesions resulting from precipitation of MIgs in the kidney as intracellular or extracellular crystals. We describe a patient with multiple myeloma (IgGλ) and diabetes who presented with nephrotic range proteinuria. Kidney biopsy revealed membranous nephropathy superimposed on diabetic glomerulosclerosis. Glomeruli were negative for PLA2R, THSD7A, and NELL-1. Ultrastructurally, the subepithelial deposits were composed of crystals (ranging from rhomboid to rod to needle shaped), which failed to stain for immunoglobulins by routine immunofluorescence but stained for IgG+λ by paraffin immunofluorescence after pronase digestion. RNA-based immunoglobulin repertoire sequencing performed on bone marrow aspirate identified an IgGλ (γ1) clone, which was highly atypical, combining an extensively mutated (23.6%) Ig heavy chain derived from the IGHV1-24 with low pI and unusual mutations and a light chain derived from an extremely rare germline gene (IGLV10-54). This report expands the pathologic spectrum of MIg crystalline nephropathies by describing a unique case of crystalline nephropathy with IgGλ deposits manifesting as membranous nephropathy., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Crystalglobulinemia is a rare syndrome characterized by intravascular crystallization of monoclonal immunoglobulins (MIg). Data on kidney involvement are limited to case reports. This series characterizes the clinicopathologic spectrum of crystalglobulin-induced nephropathy (CIN)., Study Design: Case series., Setting & Participants: Nineteen CIN cases identified from the nephropathology archives of Mayo Clinic and Columbia University. CIN was defined by intravascular (extracellular) MIg crystals visible by light microscopy (LM) and electron microscopy (EM)., Results: Among the cases, 68% were male, and 65% were Caucasian (median age, 56 years). Most patients presented with severe acute kidney injury (AKI) (median creatinine, 3.5mg/dL), hematuria, and mild proteinuria (median, 1.1g/day). Common extrarenal manifestations were constitutional (67%), cutaneous (56%), and rheumatologic (50%). Fifty percent of cases had hypocomplementemia. The hematologic disorders were monoclonal gammopathy of renal significance (MGRS) (72%), lymphoma (17%), or myeloma (11%), with 65% of these disorders discovered concomitantly with CIN. All patients had MIg identified on serum protein electrophoresis/immunofixation (IgGκ in 65%). The serum free light chain ratio was outside the renal range in 40%, and bone marrow biopsy detected the responsible clone in 67%. On LM, crystals involved glomeruli (100%) and vessels (47%), often with an inflammatory reaction (89%) and fibrin (58%). All cases exhibited crystal substructures (mostly paracrystalline) by EM. Immunofluorescence on paraffin-embedded tissue was more sensitive than frozen tissue (92% vs 47%) for demonstrating the crystal composition (IgGκ in 63%). Follow-up observation (median, 20 months) was available in 16 patients. Eighty-one percent received steroids, 44% plasmapheresis, 38% hemodialysis, and 69% chemotherapy. Ninety-percent of patients who received clone-directed therapy achieved kidney recovery versus 20% of those who did not (P=0.02)., Limitations: Retrospective design, small sample size., Conclusions: CIN is a rare cause of nephropathy associated with lymphoplasmacytic disorders (mostly MGRS) and typically presents with severe AKI and extrarenal manifestations. Diagnosis often requires immunofluorescence performed on paraffin-embedded kidney tissue. Prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional enzyme-linked immunosorbent assay (ELISA). We characterized a series of patients with atypical anti-GBM disease., Study Design: Case series., Setting & Participants: Patients identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022., Findings: Among 38 potential cases, 25 were included, of whom 14 (56%) were female and 23 (92%) had hematuria. The median serum creatinine at diagnosis was 150 (IQR, 102-203) μmol/L and median urine protein-creatinine ratio (UPCR) was 2.4 (IQR, 1.3-5.2) g/g. Nine patients (36%) had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The 9 patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at 1 year was 83% and did not appear to be associated with the light chain restriction., Limitations: Retrospective case series with a limited number of biopsies including electron microscopy., Conclusions: Compared with typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with an endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have a slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes., Plain-Language Summary: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized histologically by bright linear immunoglobulin staining along the GBM without diffuse crescentic glomerulonephritis or circulating anti-GBM antibodies. We report a case series of 25 atypical cases of anti-GBM nephritis in collaboration with the French Nephropathology Group. Compared with typical anti-GBM disease, we observed a slower disease progression. Patients frequently presented with heavy proteinuria and commonly had evidence of endocapillary or mesangial proliferative glomerulonephritis. About half of the patients displayed a monotypic immune staining pattern; they tended to be older, with less proteinuria, and commonly without glomerular crescents in biopsy specimens. No concomitant circulating monoclonal gammopathy was detected. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that can involve nearly any organ. IgG4-RD can affect the kidney in different disease patterns, collectively referred to as IgG4-related kidney disease (IgG4-RKD)., Methods: We conducted a tissue-based cohort study with clinicopathological correlation in 125 patients with IgG4-RKD., Results: The mean age at biopsy ( n  = 120) or nephrectomy ( n  = 5) was 63 years; 80% were male. One hundred eighteen patients (94%) had IgG4-related tubulointerstitial nephritis (IgG4-TIN); 20 patients (16%) had IgG4-related membranous glomerulonephritis (IgG4-MGN; 13 with concurrent IgG4-TIN). The primary clinical indication for biopsy/nephrectomy was acute or chronic renal failure in 78%, proteinuria in 17%, and mass lesion(s) in 15% (with overlap in primary indication). Fifty-two percent patients (41/79) had abnormal radiographic findings, including masses in 30% (24/79). All patients with IgG4-MGN had proteinuria. Extrarenal involvement by IgG4-RD was present in 79%. Median serum creatinine at presentation was 2.5 mg/dl (range 0.7-12). Serum IgG and/or IgG4 was increased in 91% (53/58); hypocomplementemia was present in 56% (43/77). Light microscopy showed plasma cell-rich interstitial nephritis in all cases of IgG4-TIN. Ninety-two percent of patients showed increased IgG4+ plasma cells. Seven percent showed an acute interstitial nephritis (AIN) pattern, and 5% showed non-necrotizing arteritis. Tubular basement membrane immune deposits were present in 83% of IgG4-TIN. Treatment information was available for 71 patients; 62 were treated with immunosuppression. Of those with elevated creatinine, 72% (41/57) showed a treatment response., Conclusion: This largest tissue-based series more clearly defines the disease phenotype of IgG4-RKD., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), both of which are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy (EM), DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known. We performed laser microdissection (LCM) of glomeruli followed by mass spectrometry (MS) in 12 cases each of DDD, C3GN, and pretransplant kidney control biopsies. LCM/MS showed marked accumulation of complement proteins C3, C5, C6, C7, C8, C9 and complement regulating proteins CFHR5, CFHR1, and CFH in C3GN and DDD compared to controls. C3, CFH and CFHR proteins were comparable in C3GN and DDD. Yet, there were significant differences. First, there was a six-to-nine-fold increase of C5-9 in DDD compared to C3GN. Secondly, an unexpected finding was a nine-fold increase in apolipoprotein E (ApoE) in DDD compared to C3GN. Most importantly, immunohistochemical and confocal staining for ApoE mirrored the dense deposit staining in the GBM in DDD but not in C3GN or control cases. Validation studies using 31 C3G cases confirmed the diagnosis of C3GN and DDD in 80.6 % based on ApoE staining. Overall, there is a higher burden of terminal complement pathway proteins in DDD compared to C3GN. Thus, our study shows that dense deposits in DDD are enriched with ApoE compared to C3GN and control cases. Hence, ApoE staining may be used as an adjunct to EM for the diagnosis of DDD and might be valuable when EM is not available., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Amyloidosis is a rare cause of inherited kidney disease, with most variants responsible for prominent glomerular involvement. In this issue, Kmochová et al. reported the first description of autosomal dominant medullary amyloidosis due to apolipoprotein A4 variants, resulting in slowly progressive chronic kidney disease with minimal proteinuria. Combining next-generation sequencing with histopathological studies incorporating Congo red staining and mass spectrometry should be considered in the diagnostic workup of hereditary tubulointerstitial disorders not identified after routine genetic testing., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: To report the clinicopathologic characteristics, prognostic indicators, prognosis, and transplant outcome of secondary oxalate nephropathy (ON)., Patients and Methods: We performed a retrospective analysis of 113 consecutive patients with secondary ON diagnosed at Mayo Clinic in Rochester, Minnesota, between January 1, 2001, and March 1, 2023., Results: The incidence of secondary ON among all native biopsies from Mayo Clinic patients over the study period (n=11,617) was 0.97%. ON was attributed to enteric hyperoxaluria in 60% of the 113 patients (68; most commonly Roux-en-Y gastric bypass), excessive ingestion of foods high in oxalate or oxalate precursors in 23% (26) (most commonly vitamin C), and idiopathic in 17% (19). Most patients presented with acute kidney injury (AKI) (particularly in the ingestion group) or AKI on chronic kidney disease, and 53% (60 of 113) were diabetic. Calcium oxalate crystals were accompanied by acute tubular injury, inflammation, and interstitial fibrosis and tubular atrophy. Concurrent pathologic conditions were present in 53% of the patients (60 of 113), most commonly diabetic nephropathy. After a median follow-up of 36 months, 27% of the patients (30 of 112) had kidney recovery, 19% (21 of 112) had persistent kidney dysfunction, 54% (61 of 112) had development of kidney failure, and 29% (32 of 112) died. The mean kidney survival was worse for patients with a concurrent pathologic lesion (30 months vs 96 months for those without a concurrent pathologic lesion; P<.001). Independent predictors of kidney failure were the degree of interstitial fibrosis and tubular atrophy and nadir estimated glomerular filtration rate but not the degree of crystal deposition. After a median follow-up of 58 months in 23 patients who received kidney transplant, 4 had graft loss (due to ON in 3). The 2-, 5-, and 10-year graft survivals were 90% (18 of 20), 79% (11 of 14), and 50% (6 of 12)., Conclusion: ON is a rare cause of AKI or AKI on chronic kidney disease. Most patients have comorbid pathologic conditions, particularly diabetic nephropathy, which worsen the prognosis. Recurrence in the renal allograft and graft loss may occur if hyperoxaluria is not controlled., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Some plant species may exhibit new microenvironments which lead to significant changes in the cover and diversity of the coexisting species. In this investigation, we evaluated the effects of Plantago lagopus L. on the cover and diversity of the associated plant species in the urban vegetation. A total of 70 plots were conducted in sites with- and without this species in urban gardens. Cover of the associated species and different diversity indices including species richness, Shannon-Wiener, evenness, and Simpson indices were measured. The allelopathic potential of P . lagopus was verified using its rhizosphere and non-rhizosphere soils on two target species existing within the same environment. Some soil criteria and seed sizes of the associated species were also determined. Most of the coexisting weeds were reduced in terms of their cover in plots with Plantago . The reduction of plant diversity depended on its cover. Besides, the aboveground biomass was reduced in sites comprising Plantago . The degree of inhibition was not related to the seed size of the species found. This species reduced the incident solar radiation and the local temperature over the soil surface. The locations exhibiting such species contained lower contents of available potassium and zinc. Rhizosphere soil of P . lagopus substantially inhibited germination and growth of Amaranthus viridis , but it didn't do so for Medicago lupulina . Reduction in cover, diversity, and biomass of the urban weeds associated with P . lagopus may be related to the reduction of received solar radiation, soil temperature, and nutrient availability. The allelopathic potential of P . lagopus may have a partial role in this reduction. These results suggest that P . lagopus may create a microenvironment of new conditions not favorable for most of the coexisting species., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To describe a 41-year-old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin-1 receptor antagonist (IL-1Ra) protein, anakinra, since the age of 28, who presented with golf-ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation., Methods: Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo-red staining and proteomic evaluation of microdissected Congo red-positive amyloid deposits by liquid chromatography-tandem mass spectrometry., Results: The skin, stomach, and kidney biopsies all showed the presence of Congo red-positive amyloid deposits. Mass spectrometry-based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL-1Ra protein)-type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P-component) and the amyloidogenic IL-1Ra protein, which were present in Congo red-positive areas and absent in Congo red-negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL-1Ra (anakinra) and not endogenous wild-type IL-1Ra., Conclusion: This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra)., (© 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Atypical antiglomerular basement membrane (anti-GBM) nephritis can be defined as linear GBM staining for monotypic or polytypic immunoglobulin (Ig) by immunofluorescence (IF) without a diffuse crescentic pattern. We describe the clinicopathologic features of 6 patients (18 biopsies) in this first series of recurrent atypical anti-GBM nephritis after kidney transplantation. Recurrent glomerulonephritis occurred at a mean of 3.8 months posttransplant (range 1-7 months). Three index biopsies were for clinical indication, and 3 were protocol biopsies. Glomerular histologic changes were mild, with 2 showing segmental endocapillary hypercellularity, 1 focal glomerular microangiopathy, and the others no significant glomerular histologic changes. All 6 allografts showed monotypic linear glomerular Ig staining by IF: IgG kappa (n = 2), IgG lambda, IgA kappa, IgA lambda, and IgM lambda. Follow-up biopsies were available for 5 patients and showed similar histologic and IF findings without evidence of significant progression. No patients had detectable serum anti-GBM antibody or monoclonal proteins. The mean serum creatinine level on follow-up (24-62 months posttransplant) was 1.8 (range 0.93-2.77) mg/dL; no grafts were lost to recurrent disease. This series demonstrates that monotypic atypical anti-GBM recurs in the allograft and supports the idea that this disease is due to a circulating monoclonal protein., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment., (Copyright © 2023 International Society of Nephrology and Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Drugs are an important secondary cause of membranous nephropathy (MN) with the most common drugs associated with MN being nonsteroidal anti-inflammatory drugs (NSAIDs). Since the target antigen in NSAID-associated MN is not known, we performed laser microdissection of glomeruli followed by mass spectrometry (MS/MS) in 250 cases of PLA2R-negative MN to identify novel antigenic targets. This was followed by immunohistochemistry to localize the target antigen along the glomerular basement membrane and western blot analyses of eluates of frozen biopsy tissue to detect binding of IgG to the novel antigenic target. MS/MS studies revealed high total spectral counts of a novel protein Proprotein Convertase Subtilisin/Kexin Type 6 (PCSK 6) in five of the 250 cases in the discovery cohort. A validation cohort using protein G immunoprecipitation, MS/MS, and immunofluorescence detected PCSK6 in eight additional cases. All cases were negative for known antigens. Ten of 13 cases had a history of heavy NSAID use with no history available in one case. The mean serum creatinine and proteinuria at kidney biopsy were 0.93 ± 0.47 mg/dL and 6.5 ± 3.3 gms/day, respectively. Immunohistochemistry/immunofluorescence showed granular staining for PCSK6 along the glomerular basement membrane, and confocal microscopy showed co-localization of IgG and PCSK6. IgG subclass analysis in three cases revealed codominance of IgG1 and IgG4. Western blot analysis using eluates from frozen tissue showed IgG binding to PCSK6 in PCSK6-associated but not in PLA2R-positive MN. Thus, PCSK6 may be a likely novel antigenic target in MN in patients with prolonged NSAID use., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Lysozyme-associated nephropathy (LyN), a rare cause of kidney injury in patients with chronic myelomonocytic leukemia (CMML), has not been well described to date. We report the clinicopathologic spectrum of LyN from a multi-institutional series., Method: We identified 37 native kidney biopsies with LyN and retrospectively obtained clinicopathologic data., Results: Thirty-seven patients had a median age of 74 years and included 78% males. Their most common presentation was acute kidney injury (AKI) or AKI on chronic kidney disease (CKD) (66%) with median estimated glomerular filtration rate (eGFR) of 21.7 ml/min per 1.73 m 2 , and proteinuria of 1.7 g. A minority (15%) had partial Fanconi syndrome. Serum lysozyme levels were elevated in all tested. Hematologic disorder ( n  = 28, 76%) was the most common etiology, including CMML ( n  = 15), acute myeloid leukemia ( n  = 5), and myelodysplastic syndrome (MDS) ( n  = 5). Nonhematologic causes ( n  = 5, 14%), included metastatic neuroendocrine carcinoma ( n  = 3), sarcoidosis, and leprosy. Etiology was unknown in 4 (11%). Pathology showed proximal tubulopathy with abundant hypereosinophilic intracytoplasmic inclusions, with characteristic staining pattern by lysozyme immunostain. Mortality was high (8/30). However, among the 22 alive, including 85% treated, 7 had improved kidney function, including 1 who discontinued dialysis and 6 with increase in eGFR >15 ml/min per 1.73 m 2 compared with eGFR at the time of biopsy., Conclusion: Increased awareness of the full clinicopathologic spectrum of LyN may lead to prompt diagnosis, earlier treatment, and potentially improved outcome of this rare entity., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Membranous nephropathy (MN) is the most common glomerular disease associated with sarcoidosis. The target antigen M-type phospholipase A2 receptor 1 (PLA2R) has been identified in a subset of sarcoidosis-associated MN. The target antigen is not known in the remaining sarcoidosis-associated MN., Methods: Data of patients with history of sarcoidosis and biopsy-proven MN were retrieved and analyzed. Mass spectrometry (MS/MS) was performed on all kidney biopsies of sarcoidosis-associated MN to detect the target antigens. Immunohistochemistry (IHC) studies were performed to confirm and localize the target antigens along the glomerular basement membrane (GBM)., Results: Eighteen patients with history of sarcoidosis and biopsy-proven MN were identified, of whom 3 were known to be PLA2R-negative, and in the remaining patients the target antigen was unknown. Thirteen (72%) patients were males; the median age at MN diagnosis was 54.5 years. The median proteinuria at presentation was proteinuria 9.8 g/24 h. Eight patients (44.4%) had concurrent sarcoidosis. Using MS/MS, we detected PLA2R and neural epidermal growth factor-like-1 protein (NELL1) in 7 (46.6%) and 4 (22.2%) patients, respectively. In addition, 1 case each (5.5%) was positive for thrombospondin type 1 domain-containing 7A (THSD7A), protocadherin-7 (PCDH7), and putative antigen Serpin B12. No known target antigen was detected in the remaining 4 patients (22.2%)., Conclusion: Patients with sarcoidosis and MN exhibit heterogeneous target antigens. We identified, along with PLA2R, the presence of previously unreported antigens, including NELL1, PCDH7, and THSD7A. The incidence of the target antigens in sarcoidosis appears to mirror the overall incidence of target antigens in MN. MN in sarcoidosis may be the result of a heightened immune response and is not associated with a single target antigen., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Significance Statement: Syphilis is a common worldwide sexually transmitted infection. Proteinuria may occur in patients with syphilis. Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis. The target antigen of MN in syphilis is unknown. This study shows that MN in syphilis is associated with a novel target antigen called neuron-derived neurotrophic factor (NDNF). NDNF-associated MN has distinctive clinical and pathologic manifestations and NDNF appears to be the target antigen in syphilis-associated MN., Background: Syphilis is a common sexually transmitted infection. Membranous nephropathy (MN) is a common cause of proteinuria in syphilis. The target antigen is not known in most cases of syphilis-associated MN., Methods: We performed laser microdissection of glomeruli and mass spectrometry (MS/MS) in 250 cases (discovery cohort) of phospholipase A2 receptor-negative MN to identify novel target antigens. This was followed by immunohistochemistry/confocal microscopy to localize the target antigen along the glomerular basement membrane (GBM). Western blot analyses using IgG eluted from frozen biopsy tissue were performed to detect binding to target antigen., Results: MS/MS studies of the discovery cohort revealed high total spectral counts of a novel protein, neuron-derived neurotrophic factor (NDNF), in three patients: one each with syphilis and hepatitis B, HIV (syphilis status not known), and lung tumor. Next, MS/MS studies of five cases of syphilis-MN (validation cohort) confirmed high total spectral counts of NDNF (average 45±20.4) in all (100%) cases. MS/MS of 14 cases of hepatitis B were negative for NDNF. All eight cases of NDNF-associated MN were negative for known MN antigens. Electron microscopy showed stage I MN in all cases, with superficial and hump-like deposits without GBM reaction. IgG1 was the dominant IgG subtype on MS/MS and immunofluorescence microscopy. Immunohistochemistry/confocal microscopy showed granular staining and colocalization of NDNF and IgG along GBM. Western blot analyses using eluate IgG of NDNF-MN showed binding to both nonreduced and reduced NDNF, while IgG eluate from phospholipase A2 receptor-MN showed no binding., Conclusion: NDNF is a novel antigenic target in syphilis-associated MN., (Copyright © 2023 by the American Society of Nephrology.)

Monoclonal immunoglobulin light chain (LC) crystalline inclusions within podocytes are rare, poorly characterized entities. To provide more insight, we now present the first clinicopathologic series of LC crystalline podocytopathy (LCCP) encompassing 25 patients (68% male, median age 56 years). Most (80%) patients presented with proteinuria and chronic kidney disease, with nephrotic syndrome in 28%. Crystalline keratopathy and Fanconi syndrome were present in 22% and 10%, respectively. The hematologic condition was monoclonal gammopathy of renal significance (MGRS) in 55% and multiple myeloma in 45%. The serum monoclonal immunoglobulin was IgG κappa in 86%. Histologically, 60% exhibited focal segmental glomerulosclerosis (FSGS), often collapsing. Ultrastructurally, podocyte LC crystals were numerous with variable effacement of foot processes. Crystals were also present in proximal tubular cells as light chain proximal tubulopathy (LCPT) in 80% and in interstitial histiocytes in 36%. Significantly, frozen-section immunofluorescence failed to reveal the LC composition of crystals in 88%, requiring paraffin-immunofluorescence or immunohistochemistry, with identification of kappa LC in 87%. The LC variable region gene segment, determined by mass spectrometry of glomeruli or bone marrow plasma cell sequencing, was IGKV1-33 in four and IGKV3-20 in one. Among 21 patients who received anti-plasma cell-directed chemotherapy, 50% achieved a kidney response, which depended on a deep hematologic response. After a median follow-up of 36 months, 26% progressed to kidney failure and 17% died. The mean kidney failure-free survival was 57.6 months and was worse in those with FSGS. In sum, LCCP is rare, mostly associates with IgG κappa MGRS, and frequently has concurrent LCPT, although Fanconi syndrome is uncommon. Paraffin-immunofluorescence and electron microscopy are essential to prevent misdiagnosis as primary FSGS since kidney survival depends on early diagnosis and subsequent clone-directed therapy., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Evaluation of Gastrointestinal Stromal Tumors (GIST) during initial clinical staging, surgical intervention, and postoperative management can be challenging. Current imaging modalities ( e.g. , PET and CT scans) lack sensitivity and specificity. Therefore, advanced clinical imaging modalities that can provide clinically relevant images with high resolution would improve diagnosis. KIT is a tyrosine kinase receptor overexpressed on GIST. Here, the application of a specific DNA aptamer targeting KIT, decorated onto a fluorescently labeled porous silicon nanoparticle (pSiNP), is used for the in vitro & in vivo imaging of GIST. This nanoparticle platform provides high-fidelity GIST imaging with minimal cellular toxicity. An in vitro analysis shows greater than 15-fold specific KIT protein targeting compared to the free KIT aptamer, while in vivo analyses of GIST-burdened mice that had been injected intravenously (IV) with aptamer-conjugated pSiNPs show extensive nanoparticle-to-tumor signal co-localization (>90% co-localization) compared to control particles. This provides an effective platform for which aptamer-conjugated pSiNP constructs can be used for the imaging of KIT-expressing cancers or for the targeted delivery of therapeutics.