The kidney in systemic vasculitis

2020 ◽  
pp. 4988-5001
Author(s):  
David Jayne
Keyword(s):  
Renal Disease ◽  
Immune Complex ◽  
Systemic Vasculitis ◽  
Disease Process ◽  
Rapid Progression ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Anca Associated Vasculitis ◽  
Primary Systemic Vasculitis ◽  
Complex Deposition

Systemic vasculitis can occur as a primary autoimmune disorder, or as a secondary manifestation of another disease process (related to infection, malignancy, chronic inflammatory disorder, or drugs). Primary systemic vasculitis is classified according to the predominant size of the blood vessel involved and the presence of circulating antineutrophil cytoplasm autoantibodies (ANCA). Incidence and prevalence rates are between 15 and 20 per million and 200 to 400 per million population, respectively. Vasculitic syndromes frequently involve the kidney, causing tissue infarction, loss of function, and rapid progression to endstage renal disease within weeks or months. They account for 5% of cases of endstage renal failure. ANCA-associated vasculitis is the most common cause of renal vasculitis and has been the focus for most research. Management aims for an early diagnosis, recovery of renal function, and prevention of renal relapse. Small-vessel vasculitides—renal disease is common. There are two subgroups: ANCA-associated vasculitis that comprises three syndromes: granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with angiitis (formerly Churg–Strauss syndrome). The second subgroup is immune complex vasculitis and comprises IgA vasculitis (formerly Henoch–Schönlein purpura), antiglomerular basement membrane disease, and cryoglobulinaemia: these are ANCA negative and characterized by immune complex deposition. Medium- and larger-vessel vasculitides—renal disease is uncommon in the medium-vessel disorders polyarteritis nodosa (ANCA negative) and Kawasaki’s disease, and rare in the large-vessel disorders, giant cell arteritis and Takayasu’s arteritis. This chapter discusses the aetiology and pathogenesis, pathology, clinical presentation, diagnosis, management, disease relapse, and prognosis of systemic vasculitis in detail.

The kidney in systemic vasculitis

2010 ◽  
pp. 4032-4044 ◽  
Author(s):  
David Jayne
Keyword(s):  
Systemic Vasculitis ◽  
Disease Process ◽  
Autoimmune Disorder ◽  
Rapid Progression ◽  
Inflammatory Disorder ◽  
Loss Of Function ◽  
Chronic Inflammatory Disorder ◽  
Primary Systemic Vasculitis ◽  
Stage Renal Disease ◽  
End Stage

Systemic vasculitis can occur as a primary autoimmune disorder, or as a secondary manifestation of another disease process (e.g. related to infection, malignancy, chronic inflammatory disorder, or drugs). Primary systemic vasculitis is classified according to the predominant size of blood vessel involved and the presence of circulating antineutrophil cytoplasmic autoantibodies (ANCA). Incidence and prevalence rates are between 15 and 20 per million and 200 to 400 per million population, respectively. Vasculitic syndromes frequently involve the kidney, causing tissue infarction, loss of function and rapid progression to end stage renal disease within weeks or months....

scholarly journals Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Lohit Garg ◽  
Sagar Gupta ◽  
Abhishek Swami ◽  
Ping Zhang
Keyword(s):  
Immune Complex ◽  
Systemic Vasculitis ◽  
Renal Involvement ◽  
Morphological Properties ◽  
High Dose ◽  
Cocaine Use ◽  
Immune Mediated ◽  
History Of ◽  
Psychotropic Effects ◽  
Complex Deposition

Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.

scholarly journals Interstitial Keratitis, Vertigo, and Vasculitis: Typical Cogan’s Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Ahad Azami ◽  
Nasrollah Maleki ◽  
Mohammadreza Kalantar Hormozi ◽  
Zahra Tavosi
Keyword(s):  
Hearing Loss ◽  
Systemic Vasculitis ◽  
Unknown Etiology ◽  
Inflammatory Disorder ◽  
Conjunctival Hyperemia ◽  
Cogan’S Syndrome ◽  
Auditory Brain Stem Response ◽  
Chronic Inflammatory Disorder ◽  
Cogan's Syndrome ◽  
Interstitial Keratitis

Cogan’s syndrome (CS) is a chronic inflammatory disorder of unknown etiology that most commonly affects young adults. Clinical hallmarks are bilateral interstitial keratitis and vestibuloauditory dysfunction. Association between CS and systemic vasculitis as well as aortitis also exists. The diagnosis of CS is based upon presence of characteristic inflammatory eye disease and vestibuloauditory dysfunction. We describe classic Cogan’s syndrome in a 47-year-old female from Ardabil. The patient was admitted with headache, vertigo, nausea, vomiting, right leg claudication, musculoskeletal pains, bilateral hearing loss, and blindness for the past two months. Ophthalmologic examination revealed that visual acuity was 0.1 bilaterally. Conjunctival hyperemia, bilateral cataract, and interstitial keratitis were detected with a slit lamp examination. Pure tone audiogram (PTA) and auditory brain stem response (ABR) showed bilateral sensorineural hearing loss. The other differential diagnosis of CS was studied and ruled out. Pulse i.v. methylprednisolone and cyclophosphamide were given and were followed by oral prednisolone and cyclophosphamide. Clinical follow-up showed partial improvement.

scholarly journals Regulation of inflammation by Rac2 in immune complex-mediated acute lung injury

2009 ◽  
Vol 297 (6) ◽  
pp. L1091-L1102 ◽  
Author(s):  
James L. Dooley ◽  
Dalia Abdel-Latif ◽  
Chris D. St. Laurent ◽  
Lakshmi Puttagunta ◽  
Dean Befus ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Complex ◽  
Alveolar Macrophages ◽  
Rho Gtpase ◽  
Immunohistochemical Analysis ◽  
Inflammatory Disorder ◽  
Chemokine Production ◽  
Neutrophil Degranulation ◽  
Complex Deposition

Acute lung injury (ALI) is an inflammatory disorder associated with recruitment and activation of neutrophils in lungs. Rac2, a member of the Rho GTPase subfamily, is an essential regulator of neutrophil degranulation, superoxide release, and chemotaxis. Here, we hypothesized that Rac2 is important in mediating lung injury. Using a model of IgG immune complex-mediated ALI, we showed that injury was attenuated in rac2−/−mice compared with wild-type (WT) mice undergoing ALI, with significant decreases in alveolar leukocyte numbers, vascular leakage, and the inflammatory mediators, myeloperoxidase (MPO) and matrix metalloproteinases (MMPs). Reduced injury in rac2−/−mice was not associated with diminished cytokine and chemokine production, since bronchoalveolar lavage (BAL) levels of IL-17, TNF, CCL3, CXCL1, and CXCL2 were similarly increased in WT and rac2−/−mice with ALI compared with sham-treated mice (no ALI). BAL levels of MMP-2 and MMP-9 were significantly decreased in the airways of rac2−/−mice with ALI. Immunohistochemical analysis revealed that MMP-2 and MMP-9 expression was evident in alveolar macrophages and interstitial neutrophils in WT ALI. In contrast, MMP-positive cells were less prominent in rac2−/−mice with ALI. Chimeric mice showed that Rac2-mediated lung injury was dependent on hematopoietic cells derived from bone marrow. We propose that lung injury in response to immune complex deposition is dependent on Rac2 in alveolar macrophages and neutrophils.

scholarly journals Autoantibodies Against Lysosome Associated Membrane Protein-2 (LAMP-2) in Pediatric Chronic Primary Systemic Vasculitis

2021 ◽  
Vol 11 ◽  
Author(s):  
Kristen M. Gibson ◽  
Renate Kain ◽  
Raashid A. Luqmani ◽  
Colin J. Ross ◽  
David A. Cabral ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Renal Disease ◽  
Disease Activity ◽  
Pediatric Patients ◽  
Systemic Vasculitis ◽  
Small Vessel Vasculitis ◽  
Creatinine Concentration ◽  
Primary Systemic Vasculitis ◽  
Adults And Children

BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis in adults and children that commonly affects the kidneys. Although the frequent antigenic, and presumed pathogenic, targets of ANCA in AAV are proteinase-3 (PR3) and myeloperoxidase (MPO), ANCA against lysosome associated membrane protein-2 (LAMP-2), a lesser known ANCA antigen that is expressed on the glomerular endothelium, are present in some adults with AAV-associated renal disease. LAMP-2-ANCA has not been assessed in children with chronic systemic vasculitis, and, if present, would be a potentially valuable biomarker given that treatment decisions for these pediatric patients at diagnosis are largely informed by kidney function.MethodsA custom ELISA, using commercially available reagents, was designed to detect autoantibodies to human LAMP-2 in serum. Sera obtained from 51 pediatric patients at the time of diagnosis of chronic primary systemic vasculitis (predominantly AAV) were screened. LAMP-2-ANCA titers were evaluated for correlation with clinical metrics of disease activity (pediatric vasculitis activity score [pVAS], C-reactive protein [CRP] concentration, and erythrocyte sedimentation rate [ESR]), MPO- and PR3-ANCA titers, and renal function (glomerular filtration rate [GFR], renal-specific pVAS, and serum creatinine concentration).ResultsLAMP-2-ANCA (>1,000 ng/ml) were detected in 35% (n = 18) of pediatric systemic vasculitis patients, of which, 10 (20% of all patients) were found to have high positive titers (>1,500 ng/ml). Undetectable or negative titres (<500 ng/ml) were identified in 12% (n = 6) of patients, those with titers between 500 and 1,000 ng/ml were considered low with unknown clinical relevance (53%, n = 27). Although LAMP-2-ANCA titers did not significantly differ between patients with AAV versus ANCA-negative vasculitis, only AAV patients had high concentrations (>1,500 ng/ml) of LAMP-2-ANCA. LAMP-2-ANCA titers did not correlate with measures of disease activity (pVAS, CRP, or ESR) at the time of diagnosis. In contrast, for patients with 12-month post diagnosis follow-up, a negative correlation was observed between the change in GFR (from diagnosis to 12-month follow-up) and LAMP-2-ANCA titer at diagnosis.ConclusionsModerate to high LAMP-2-ANCA titers were detected in 35% (18/51) of children with chronic systemic vasculitis affecting small-to-medium vessels. Although the highest concentrations of LAMP-2-ANCA in this population were observed in individuals positive for classic ANCA (MPO- or PR3-ANCA), similar to previous reports on adult patients, LAMP-2-ANCA titers do not correlate with classic ANCA titers or with overall disease activity at diagnosis. Renal disease is a common manifestation in systemic small-medium vessel vasculitis (both in adults and children, though more severe in children) and our preliminary data suggest LAMP-2-ANCA at diagnosis may be a risk factor for more severe renal disease.

Localization of Immune Complexes in the Basement Membrane of the Ductuli Efferentes of the Rhesus Monkey

1980 ◽  
Vol 38 ◽  
pp. 456-457
Author(s):  
D. Marsh
Keyword(s):  
Basement Membrane ◽  
Fluorescence Microscopy ◽  
Rhesus Monkey ◽  
Immune Complex ◽  
Immune Complexes ◽  
Vas Deferens ◽  
Frozen Sections ◽  
Efferent Ducts ◽  
Complex Deposition ◽  
Sperm Antibodies

As a result of vasectomy, spermatozoa are confined to the epididymis and vas deferens, where they degenerate, releasing antigens that enter the circulation or are engulfed by macrophages. Multiple antigens of the sperm can elicit production of autoantibodies; circulating anti-sperm antibodies are found in a large percentage of vasectomized men, indicating the immunogenicity of the sperm. The increased prevalence of macrophages in the liomen of the rhesus monkey testicular efferent ducts after vasectomy led to further study of this region. Frozen sections were used for evaluation of immunopathological status by fluorescence microscopy with fluorescein-conjugated antibody. Subsequent granular deposits of immune complexes were revealed by positive immunofluorescence staining for complement. The immune complex deposition in the basement membrane surrounding the efferent ducts implies that this region is involved in antigen leakage (Fig. 1).

scholarly journals Redox Imbalance in T Cell-Mediated Skin Diseases

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Saveria Pastore ◽  
Liudmila Korkina
Keyword(s):  
Oxidative Stress ◽  
Atopic Dermatitis ◽  
Contact Dermatitis ◽  
Skin Diseases ◽  
Redox Balance ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Physical Chemical ◽  
Chemical Oxidants ◽  
Beneficial Outcome

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.

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