Case series of idiopathic intracranial hypertension in three patients with immune-complex glomerulonephritis.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is defined by an increased cerebrospinal fluid pressure in the absence of inflammation, structural obstructions, or mass lesions. Although the underlying pathogenesis of IIH is not fully understood, associations with specific risk factors as obesity, obstruction of cerebral venous sinuses, medications, endocrine or systemic conditions and chronic kidney disease have been described. Immune-complex glomerulonephritis as IgA-nephropathy is a frequent cause of chronic kidney failure, which was reported previously in one IIH patient. To date, there is no knowledge about the variable relation of immune-complex nephritis, kidney function and the course of IIH. CASE PRESENTATION: We report three cases (two females) of concurrent diagnosis of IIH and immune-complex glomerulonephritis. All patients presented with typical IIH symptoms of headache and visual disturbances. Two patients had been diagnosed with IgA-nephropathy only few weeks prior to IIH diagnosis. The third patient had been diagnosed earlier with terminal kidney failure due to a cryoglobulin glomerulonephritis. CONCLUSION: We propose a possible link between renal deposition of immune-complexes and increased cerebrospinal fluid pressure. Pathophysiological hypotheses and clinical implications are discussed. We recommend clinical awareness and further systematic research to obtain more information on the association of IIH and immune-complex glomerulonephritis.

Asociación entre pancreatitis autoinmune y colitis ulcerosa: descripción de 12 pacientes / No disponible

INTRODUCCIÓN: las manifestaciones pancreáticas en enfermedad inflamatoria intestinal (EII) incluyen principalmente pancreatitis aguda secundaria a fármacos y, con menor frecuencia, pancreatitis autoinmune. Existe asimismo una asociación particular con la pancreatitis autoinmune tipo 2. MÉTODOS: estudio retrospectivo de pacientes con diagnóstico de colitis ulcerosa (CU) y pancreatitis autoinmune (PAI) en control en dos centros en Santiago de Chile, entre los años 2007 y 2018. Se registraron datos clínicos, resultados de laboratorio e imágenes, evolución en el tiempo y tratamientos utilizados. RESULTADOS: se identificaron 12 pacientes con ambas enfermedades, la edad promedio fue 34 años, con un 42 % de sexo masculino. En todos los casos se estableció el diagnóstico probable de PAI tipo 2 en base a la resonancia magnética (RM) de páncreas, la asociación con EII y la rápida respuesta a tratamiento con corticoides. En dos casos se tomaron muestras para estudio histológico pero el resultado fue no concluyente. Se observó recurrencia de la PAI en un solo caso. El 58 % de los pacientes tenían una CU extensa, el 100 % recibe tratamiento con 5-ASA y el 33 %, con azatioprina. Solo un paciente tuvo un brote grave y ninguno presentó complicaciones, necesidad de tratamiento con biológicos ni cirugía. CONCLUSIÓN: en nuestra casuística se confirma la asociación entre CU y PAI tipo 2. No se observó mayor severidad de la EII en este grupo de pacientes

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Type 3 hypersensitivity in COVID-19 vasculitis.

Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.

Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN.

Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment.

Manifestations of Complement-Mediated and Immune Complex-Mediated Membranoproliferative Glomerulonephritis: A Comparative Consecutive Series.

PURPOSE: Membranoproliferative glomerulonephritis (MPGN) recently was reclassified to reflect the underlying cause as a complement-mediated and immune complex-mediated disease. This classification is based on renal biopsy immunofluorescence examination, making the former electron-microscopy classification obsolete. In this report, we describe related eye findings in patients with MPGN based on the new classification. DESIGN: Retrospective case series. PARTICIPANTS: All Mayo Clinic Rochester patients with pathology-confirmed complement- and immune complex-mediated MPGN who had available ophthalmology records from 1997 through 2014 were included in this study. METHODS: The medical and pathologic records of patients with MPGN and eye examination results were reviewed from years 1997 through 2014. MAIN OUTCOME MEASURES: The number of patients and the number of eyes with MPGN-related pathologic features were examined. Visual acuity also was considered. RESULTS: There were 23 patients with complement-mediated MPGN and available eye examination results. Of these, 9 patients (39%) and 17 eyes (37%) had retinal pathologic features that likely were related to the same underlying pathophysiologic process as their renal disease. Five patients (22%) and 6 eyes (13%) had significant vision loss. There were 23 patients with immune complex-mediated MPGN and available eye examination results. Only 2 (9%) of these patients (4 eyes) had retinal pathologic features that potentially could be related to the same underlying pathophysiologic process as their renal disease, and neither had vision loss. CONCLUSIONS: Retinal abnormalities are more prominent among patients with complement-mediated MPGN when compared with patients with immune complex-mediated MPGN. It is critical for ophthalmologists to recognize the updated MPGN classification system, and all patients with complement-mediated MPGN require screening eye examinations.

Membranoproliferative glomerulonephritis recurrence after kidney transplantation: using the new classification.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon glomerular disorder that may lead to end stage renal disease (ESRD). With new understanding of the disease pathogenesis, the classical classification as MPGN types I, II, III has changed. Data on post-transplant MPGN, in particular with the newly refined classification, is limited. We present our center's experience of MPGN after kidney transplantation using the new classification. METHODS: This is a retrospective study of 34 patients with ESRD due to MPGN who received 40 kidney transplants between 1994 and 2014. We reviewed the available biopsies' data using the new classification. We assessed post transplantation recurrence rate, risk factors of recurrence, the response to therapy and allografts' survival. RESULTS: Median time of follow up was 5.3 years (range 0.5-14 years). Using the new classification, we found that pre-transplant MPGN disease was due to immune complex-mediated glomerulonephritis (ICGN) in 89 % of cases and complement-mediated glomerulonephritis (CGN) in 11 %. Recurrence was detected in 18 transplants (45 %). Living related allografts (P = 0.045), preemptive transplantations (P = 0.018), low complement level (P = 0.006), and the presence of monoclonal gammopathy (P = 0.010) were associated with higher recurrence rate in ICGN cases. Half of the patients with recurrence lost their allografts. The use of ACEi/ARB was associated with a trend toward less allograft loss. CONCLUSIONS: MPGN recurs at a high rate after kidney transplantation. The risk of MPGN recurrence increases with preemptive transplantation, living related donation, low complement level, and the presence of monoclonal gammopathy. Recurrence of MPGN leads to allograft failure in half of the cases.

Bullous Pemphigoid With a Dual Pattern of Glomerular Immune Complex Disease.

A 75-year-old man presented with a blistering skin disease and nephrotic syndrome. Bullous pemphigoid was diagnosed by linear immunoglobulin G (IgG) and C3 staining along the basement membrane zone of a skin biopsy specimen and by the presence of circulating IgG recognizing the 180-kDa bullous pemphigoid antigen (BP180; type XVII collagen). A kidney biopsy specimen showed endocapillary inflammation without crescents. Direct immunofluorescence showed strong IgG and C3 staining in a combined granular and linear pattern along the glomerular basement membrane. Electron microscopy showed subepithelial deposits. In serum, no antibodies against the Goodpasture antigen (type IV collagen) or phospholipase A2 receptor were detected. Indirect immunofluorescence studies using the patient's serum showed a strikingly linear but not granular IgG pattern along the epithelial basement membranes of monkey esophagus and kidney. Although type XVII collagen was recently identified in the glomerulus, the patient's serum did not produce a 180-kDa band on immunoblot of kidney tissue and still stained glomeruli of BP180 knockout mice by indirect immunofluorescence. The patient was treated with prednisone and azathioprine, which resulted in complete remission of skin and kidney manifestations. Although bullous pemphigoid has been reported previously in association with anti-glomerular basement membrane disease or membranous nephropathy, this case demonstrates both elements in 1 patient. This concurrence and the linear pattern on indirect immunofluorescence support the possibility of cross-reactive or parallel autoantibodies to basement membranes with a secondary membranous component.

Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex-mediated inflammation in mice.

Platelets protect vascular integrity during inflammation. Recent evidence suggests that this action is independent of thrombus formation and requires the engagement of glycoprotein VI (GPVI), but it remains unclear how platelets prevent inflammatory bleeding. We investigated whether platelets and GPVI act primarily by preventing detrimental effects of neutrophils using models of immune complex (IC)-mediated inflammation in mice immunodepleted in platelets and/or neutrophils or deficient in GPVI. Depletion of neutrophils prevented bleeding in thrombocytopenic and GPVI(-/-) mice during IC-mediated dermatitis. GPVI deficiency did not modify neutrophil recruitment, which was reduced by thrombocytopenia. Neutrophil cytotoxic activities were reduced in thrombocytopenic and GPVI(-/-) mice during IC-mediated inflammation. Intravital microscopy revealed that in this setting, intravascular binding sites for platelets were exposed by neutrophils, and GPVI supported the recruitment of individual platelets to these spots. Furthermore, the platelet secretory response accompanying IC-mediated inflammation was partly mediated by GPVI, and blocking of GPVI signaling impaired the vasculoprotective action of platelets. Together, our results show that GPVI plays a dual role in inflammation by enhancing neutrophil-damaging activities while supporting the activation and hemostatic adhesion of single platelets to neutrophil-induced vascular breaches.

[Interest of allergy tests in urticaria]. / Place du bilan allergologique dans l'urticaire.

Urticaria is a common skin disease that may affect 20 % of the general population. Most of the time, urticaria is an acute disorder that rarely can be chronic. The difficulty in urticaria is not the clinical diagnosis because the rash is characteristic, but the underlying causes and treatment that result. Urticaria is a benign disease when chronic and potentially dangerous when acute and associated with allergy. This allergy risk, needs an allergy exploration, based on skin tests and / or specific IgE assays. Because allergy is unusual in chronic urticaria, no allergy tests should be performed. By contrast, these tests must be undertaken in case of acute urticaria with a strong suspicion of IgE-mediated reaction because of the risk of severe anaphylaxis in case of allergenic re-exposure.

Goodpasture's syndrome with concomitant immune complex mixed membranous and proliferative glomerulonephritis.

Classical Goodpasture's (GP) syndrome is a monophasic illness characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis with linear IgG deposition along the glomerular and distal tubular basement membrane and estructive necrotizing diffuse extracapillary crescentic glomerulonephritis. The majority of patients have circulating anti-glomerular basement membrane (GBM) antibodies, detectable with standard anti-GBM ELISA. Concurrence of GP syndrome with proliferative glomerulonephritis has only rarely been described. In this report, for the first time we describe in a 21-year-old woman GP syndrome with 50% crescentic sclerosing glomerulonephritis with linear immunofluorescence characteristic of anti-GBM pathogenesis, combined with mixed membranous and membranoproliferative glomerulonephritis with granular immunofluorescence and subepithelial, mesangial and subendothelial deposits characterizing immune complex pathogenesis. The clinical picture was also unusual for GP syndrome, manifesting a recurrent but non-progressive course, nephrotic syndrome, normal renal function and low values of anti-GBM antibodies, identified only by novel more sensitive techniques.

Comparison of risk factors and outcomes in HIV immune complex kidney disease and HIV-associated nephropathy.

BACKGROUND AND OBJECTIVES: HIV-associated nephropathy (HIVAN) is well described, but the clinical features of a group of renal pathologies characterized by Ig or immune complex depositions referred to as HIV-associated immune complex kidney disease (HIVICK) have not been well established. The objective of this study is to assess risk factors for HIVICK compared with contemporaneous control participants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A nested case-control study of 751 HIV-infected patients followed from January 1996 to June 2010 was conducted. Groups were compared using the chi-squared test or rank-sum analysis. Conditional logistic regression was used to estimate odds ratios (ORs) for HIVICK. Incidences of overall ESRD and with/without combined antiretroviral therapy (cART) exposure were calculated. RESULTS: HIVICK patients were predominantly African American (92%). Compared with matched controls, patients with HIVICK were more likely to have HIV RNA >400 copies/ml (OR, 2.5; 95% confidence interval [95% CI], 1.2 to 5.2), diabetes (OR, 2.8; 95% CI, 1.1 to 6.8), and hypertension (OR, 2.3; 95% CI, 1.2 to 4.5). Compared with HIVAN, patients with HIVICK had more antiretroviral therapy exposure, lower HIV viral loads, and higher CD4 and estimated GFR. ESRD was less common in the HIVICK versus the HIVAN group (30% versus 82%; P<0.001), and the use of cART was not associated with ESRD in HIVICK patients (25% versus 26; P=0.39). CONCLUSIONS: HIVICK was predominantly observed in African-American patients and associated with advanced HIV disease. ESRD incidence is lower in HIVICK patients compared with those with HIVAN. Unlike HIVAN, cART use was not associated with the incidence of ESRD in HIVICK.

Immune-complex-like disease in the course of Enterobacter cloacae sepsis due to cholelithic cholecystitis preceded by influenza vaccination.

This case report describes a 52-y-old male patient who, one week after influenza vaccination, presented with abdominal symptoms: pain in the right epigastrium followed by liver dysfunction and pyrexia, as well renal failure, muscles pain and consciousness disorders. Immune-complex-like disease and Enterobacter cloacae sepsis due to cholelithic cholecystitis were diagnosed. In this case, a correlation between vaccination and immune complex-like-disease was suspected based on the onset of symptoms a few days after vaccination and clinical improvement after plasmapheresis. The etiopathogenesis of immune-complex-like disease in this case possibly could relate to the similarity of the vaccine antigens and E. cloacae antigens as well a genetic predisposition.

The impact of hepatitis C coinfection on kidney disease related to human immunodeficiency virus (HIV): a biopsy study.

Approximately 1 in 4 individuals infected with the human immunodeficiency virus (HIV) in the United States is coinfected with the hepatitis C virus. Both conditions increase the risk for the development and progression of kidney disease. The effect, however, of coexisting HIV and hepatitis C infection on the spectrum and progression of kidney disease is not well known. To compare the clinical features, histopathologic kidney diagnoses, and proportion of individuals progressing to end-stage kidney disease (ESKD), we reviewed the clinical records of HIV-infected individuals with and without hepatitis C coinfection who underwent ultrasound-guided percutaneous kidney biopsies between February 7, 1995, and March 30, 2009.Of the 249 HIV-infected individuals included in this study, 58% were coinfected with hepatitis C. Coinfected individuals were older (mean age, 46 ± 7 vs. 44 ± 10 yr, respectively; p < 0.01) and more likely to have used illicit drugs (85% vs. 14%, respectively; p < 0.01) compared to HIV-infected individuals without hepatitis C. HIV-associated nephropathy was the most common histopathologic diagnosis in both groups. Immune-complex glomerulonephritides (ICGNs), including lupus-like nephritis, postinfectious glomerulonephritis, membranous glomerulopathy, membranoproliferative glomerulonephritis, IgA nephropathy, and nonspecific ICGNs, occurred more frequently in individuals coinfected with hepatitis C than in those not coinfected (22% vs. 11%, respectively; p = 0.02). Although the proportion of those who died was similar between the 2 groups, hepatitis C coinfection was independently associated with a greater risk of progression to ESKD (hazard ratio, 1.81; 95% confidence interval, 1.09-2.99; p = 0.02).The current study demonstrates that coinfection with hepatitis C in individuals infected with HIV predisposes these individuals to immune-complex glomerulonephritides and is associated with increased risk of ESKD in the biopsied population.

HIV-associated immune complex glomerulonephritis with "lupus-like" features.

Renal structural abnormalities in HIV/AIDS infected patients have been infrequently and incompletely reported in patients from sub-Saharan Africa. We report an immune complex glomerulonephritis with "lupus-like" features in a ten-year-old HIV+ boy who was evaluated at the University Hospital of Kinshasa. The light microscopic examination of the renal biopsy displayed a predominantly membranoproliferative glomerulonephritis with prominent focal segmental necrotizing injury, numerous wire-loops, and a spiky membranous nephropathy. In addition, there were prominent tubular injury, microcysts filled with periodic acid-Schiff (PAS) positive casts, edema and an inflammatory infiltrate of the interstitium, features of a classic HIV-associated nephropathy (HIVAN). Electron microscopy revealed large subendothelial, intra-membranous, subepithelial and mesangial deposits. The combination of these findings, while being consistent with lupus nephritis WHO grade IV/V, the tubulointerstitial HIVAN-like changes and the absence of clinical evidence of lupus disease favored an HIV-associated immune complex glomerulonephritis with "lupus-like features".

[Therapy-refractory thrombocytopenia in a 28-year-old patient]. / Therapierefraktäre Thrombozytopenie bei einem 28-jährigen Patienten.

We report a case of a patient with thrombocytopenia. A sporadic MYH9-associated disease, May Hegglin anomaly, was identified by giant platelets, leucocyte inclusion bodies and the typical distribution of NMMHC-IIA in granulocytes in the absence of impaired renal function, cataract and hearing loss. MYH9-associated diseases are an underestimated differential diagnosis of idiopathic thrombocytopenia. The correct diagnosis is important to prevent unnecessary treatment of a patient with thrombocytopenia and to provide sufficient patient information and genetic counseling. Therefore, careful examination of the blood smear has to be the first diagnostic step in a case of unexplained thrombocytopenia.

Type III hypersensitivity to insulin leading to leukocytoclastic vasculitis.

Here, we report the occurrence of leukocytoclastic vasculitis as an outcome of type III allergy to insulin in a patient with type II diabetes mellitus. The diagnosis was made on the basis of anatomo-pathological examination of a skin biopsy.

Fibrillary glomerulonephritis with hepatitis C viral infection and hypocomplementemia.

Fibrillary glomerulonephritis (FGN) is a relatively rare cause of renal disease, found in only 0.6-1.5% of native renal biopsies. The pathogenesis of FGN is not well described, and very few associations with disease processes other than hepatitis C virus (HCV) have been made. We describe a case that provides evidence in support of the FGN-HCV association, as well as introduces the association of FGN-HCV and hypocomplementemia. The case is a 53-year-old African-American female demonstrating a classical presentation of FGN complicated by a concomitant HCV infection. Treating an HCV infection with alpha-interferon has been shown to result in subsequent improvement in the nephrotic syndrome and renal function. However, this patient is unique in that she is complicated with hypocomplementemia, creating a complex treatment situation.