RESUMEN

Introduction: Cryoglobulinemia refers to the presence of cryoglobulins (CGs) in the serum, encompassing a group of diseases caused by the type of circulating GC. Cryoglobulinemic glomerulonephritis (CryoGN) is the principal manifestation of renal involvement. The diagnosis may be challenging because the hallmark of cryoglobulinemia is the detection of CG in the serum. However, cases of CryoGN without serological evidence of CGs are not uncommon in clinical practice, often diagnosed by anatomopathological findings in the renal biopsy. Case Presentation: We report the case of an 86-year-old male who developed renal impairment, nephritic syndrome, and nephrotic-range proteinuria, without serological evidence of CGs, associated with staphylococcal bacteremia without apparent focus. Renal biopsy and pathological examination showed a membranoproliferative glomerulonephritis pattern with CD61-negative pseudothrombi. Immunofluorescence microscopy showed atypical IgA-dominant deposits. Electron microscopy revealed amorphous subendothelial and mesangial deposits and organized electrodense deposits within capillary loops (pseudothrombi) with microtubular substructure measuring 20-40 nm in thickness. These findings were consistent with seronegative CryoGN and microtubular organized atypical IgA-dominant deposits. Discussion: In this report, we discuss the clinical, analytical, and histopathological findings of a rare case of CryoGN without serological evidence of CGs. Regarding the etiology that triggered the glomerular disease in our patient, we conducted an exhaustive study in order to determine the underlying cause of CryoGN. At the time of biopsy, the patient had an active staphylococcal bacteremia. There are reports that postulate that staphylococcal antigens drive activation of immune system and in consequence, could cause this rare form of IgA-dominant glomerulonephritis with cryoglobulinemic features. After ruling out other causes of cryoglobulinemia, we discuss a plausible causal relationship of the staphylococcal infection in the pathogenesis of CryoGN in our patient.

RESUMEN

Introducción: El lupus eritematoso sistémico juvenil (LESJ) es una enfermedad autoinmunitaria, multisistémica, caracterizada por la producción de autoanticuerpos y el desarrollo frecuente de glomerulonefritis mediada por inmunocomplejos. La nefritis lúpica es una complicación frecuente y grave del LESJ, con alta morbilidad, siendo causa de insuficiencia renal terminal en muchos de estos pacientes. La nefropatía por IgA representa la etiología más común en la población general y raramente se asocia con LESJ. Caso clínico: adolescente femenino con LESJ en quien se diagnosticó nefritis no lúpica (nefropatía por IgA). Conclusiones: El diagnóstico anatomopatológico es clave para establecer el pronóstico y planificar el tratamiento.

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Introduction: Juvenile systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease characterized by the production of autoantibodies and the frequent development of immune complex-mediated glomerulonephritis. Lupus nephritis is a frequent and serious complication of JSLE, has a high associated morbidity rate, and is the cause of end-stage renal failure in many of these patients. IgA Nephropathy represents the most common etiology in the general population and is rarely associated with JSLE. Clinical case: a female adolescent with JSLE who was diagnosed with non-lupus nephritis (IgA nephropathy). Conclusions: The anatomopathological diagnosis is key to establish the prognosis and plan the treatment.

RESUMEN

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. It is diagnosed based on clinical and histological features including predominant IgA deposits in kidney biopsy. The multi-hit theory, based on the production of GDIgA1 and anti-GDIgA1 antibodies, and complement activation via alternative and lectin pathways and also a genetic tendency are crucial in the pathogenesis of IgAN. The aim of the present review is to summarize the utility of routine diagnostic tests in IgA nephropathy, such as IgA and C3 in serum and kidney biopsy specimens, for predicting the disease progression. The paper also contains data on new markers used in the diagnosis and prognosis of IgA nephropathy.

Asunto(s)

Glomerulonefritis por IGA , Humanos , Glomerulonefritis por IGA/patología , Inmunoglobulina A , Biomarcadores , Riñón/patología , Biopsia

RESUMEN

Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh 1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2-3 lesion. Seventy-five pediatric patients were split into three groups according to the final diagnosis: (i) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis; none presented intestinal anti-TG2 IgA deposits; (ii) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in seven and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and (iii) 47 children with Marsh 2-3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low-grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.

Asunto(s)

Enfermedad Celíaca , Autoanticuerpos , Biopsia , Niño , Proteínas de Unión al GTP , Humanos , Inmunoglobulina A , Mucosa Intestinal , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas

RESUMEN

BACKGROUND: The purpose of the current study was to describe the clinico-pathological characteristics and outcomes in patients with lupus nephritis with IgA deposits in the kidneys. METHODS: A total of 258 patients with lupus nephritis with complete clinical data and follow-up was enrolled. They were divided into two groups: the IgA deposits group and the non-IgA deposits group. Their clinico-pathological features and outcomes between the two groups were further compared. RESULTS: Patients with IgA deposits had significantly lower prevalence of acute kidney failure, higher eGFR, lower plasma levels of C3a, and lower renal pathological chronicity indices scores than those with non-IgA deposits (19.4% vs. 31.8%, 86.2 [52.8, 110.7] vs. 77.6 [32.2, 101.7] ml/min/1.73m2, 1045.48 [559.41, 1796.34] vs. 1920.77 [1155.08, 2986.96]ng/ml, and 2 [1, 3] vs. 2.5 [2, 4], respectively, all P < 0.05). Patients with IgA deposits also had a higher frequency of the CFH rs6677604-AA/GA genotype in comparison with those with non-IgA deposits (12.0% vs. 8.2%, P = 0.469). Using the multivariable Cox hazard analysis, the IgA deposits were identified as a protective factor of survival from the composite events (HR 0.423; 95% CI, 0.219 to 0.816; P = 0.01). CONCLUSIONS: Patients with IgA deposits presented with milder renal damage and a good prognosis, which suggested its protective role in lupus nephritis.

Asunto(s)

Nefritis Lúpica , Femenino , Humanos , Inmunoglobulina A , Riñón/patología , Nefritis Lúpica/complicaciones , Nefritis Lúpica/epidemiología , Masculino

RESUMEN

An association between celiac disease and IgA nephropathy (IgAN) has been suggested. In celiac disease, in addition to circulating in serum, IgA-class tissue transglutaminase (tTG) autoantibodies are deposited in the small bowel mucosa and extraintestinal organs. In this case series of IgAN patients with or without celiac disease, we studied whether celiac disease-type IgA-tTG deposits occur in kidney biopsies. The study included nine IgAN patients, four of them with celiac disease. At the time of the diagnostic kidney biopsy serum tTG autoantibodies were measured and colocalization of IgA and tTG was investigated in the frozen kidney biopsies. Three IgAN patients with celiac disease had IgA-tTG deposits in the kidney even though in two of these the celiac disease diagnosis had been set years later. These deposits were not found in a patient with already diagnosed celiac disease following a gluten-free diet. Of the five non-celiac IgAN patients, three had IgA-tTG deposits in the kidney. We conclude that tTG-targeted IgA deposits can be found in the kidney biopsies of gluten-consuming IgAN patients but their specificity to celiac disease seems limited.

Asunto(s)

Autoanticuerpos/sangre , Biopsia , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Proteínas de Unión al GTP/inmunología , Glomerulonefritis por IGA/patología , Riñón/patología , Transglutaminasas/inmunología , Adulto , Dieta Sin Gluten , Femenino , Glútenes , Humanos , Inmunoglobulina A/sangre , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Proteína Glutamina Gamma Glutamiltransferasa 2 , Estudios Retrospectivos , Adulto Joven

RESUMEN

PURPOSE: To describe a case series of scleritis associated with IgA vasculitis (IgAV) at a tertiary referral center. OBSERVATIONS: Three men with scleritis associated with IgAV were identified: one with anterior scleritis alone, one with anterior scleritis and peripheral ulcerative keratitis (sclerokeratitis), and one with anterior and posterior scleritis. Visual acuity was preserved except from the patient who developed posterior scleritis. Ocular pain was the main symptom at presentation. All patients had a previous history of palpable purpura, but only one was aware of his underlying IgAV. Laboratory results revealed microhematuria and proteinuria with normal urinary ß2 microglobulin levels and negative serum ANCAs. Skin or kidney biopsy demonstrated leukocytoclastic vasculitis or glomerulonephritis with dominant IgA immune deposits. CONCLUSIONS AND IMPORTANCE: Although uncommon, IgAV should be included in the differential diagnosis of anterior scleritis alone or associated with peripheral ulcerative keratitis or posterior scleritis, even in systemically asymptomatic patients. Urinalysis should not be underestimated in assessment of scleritis to detect early stages of glomerular disease. Scleritis may be the first manifestation whose study may lead to the diagnosis of IgAV. Multidisciplinary approach is necessary to prevent irreversible organ damage such as renal failure.

RESUMEN

BACKGROUND: Maternally inherited diabetes and deafness (MIDD), a mitochondrial genetic disorder, typically affects the kidneys and results in end-stage renal disease. Early diagnosis of MIDD is challenging when renal manifestations precede other key clinical features such as diabetes and deafness and/or when the disease is complicated by other renal pathologies. CASE PRESENTATION: Here, we present the case of a 33-year-old Japanese woman who had initially been diagnosed with IgA nephropathy but was found to have MIDD 6 years later. Two renal biopsies were conducted six years apart. While assessment of the first biopsy specimen with the monoclonal antibody (KM55) revealed mesangial IgA deposits (containing the galactose-deficient IgA1 variant [Gd-IgA1]), examination of the second specimen showed no mesangial IgA deposits and newly-developed glomerular global scleroses and tubular damage. Granular swollen epithelial cells (GSECs), characterised by abnormal mitochondria, were observed among the tubules and collecting ducts in both biopsy specimens. Mitochondrial DNA analysis revealed an m.3243A > G mutation. CONCLUSIONS: We rediscovered the usefulness of GSECs as a pathologically distinctive feature of mitochondrial nephropathy and reviewed the literature regarding MIDD complicated by mesangial IgA deposition. Furthermore, we demonstrate that the mesangial IgA deposits in this patient consisted of the galactose-deficient IgA1 variant. The monoclonal antibody (KM55) might be a useful tool to distinguish IgAN from latent IgA deposits.

Asunto(s)

Sordera/complicaciones , Sordera/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Galactosa/deficiencia , Inmunoglobulina A/análisis , Células Mesangiales/patología , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/diagnóstico , Adulto , Sordera/genética , Diabetes Mellitus Tipo 2/genética , Femenino , Humanos , Células Mesangiales/química , Células Mesangiales/ultraestructura , Enfermedades Mitocondriales/genética , Linaje

RESUMEN

IgA nephropathy is the most common glomerulonephritis in the world. For diagnosis kidney biopsy is necessary. AIM: The aim of the study was assessment the significance of IgA, C3 and IgG deposits intensity and location in kidney childhood IgA nephropathy (IgAN) for the symptoms of the disease and the follow up. MATERIALS AND METHODS: Study population consisted of 81 children, average 11,45±3,99 years. IgAN was recognized based on renal biopsy, performed 1,2±1,84, median 0,5 years after the onset. We used Oxford classification (OC) to assess the severity of histopatological lesions. In renal biopsy IgA and C3 deposits were found in immunofluorescence in mesangium or in vessels of glomeruli or both, and intensity was defined 0 to +4. We analyzed: proteinuria (mg/kg/day), hematuria, creatinine, GFR (according to Schwartz formula) two times, at the onset of the disease (OOD) and at the follow up (FU). Patients were treated with: ACEI/ARB or steroids alone or with imunossupresion drugs: azathioprine (AZA), cyclophosphamide (CYC), cyclosporine A (CsA), mycopnenolate mophetil (MMF). The follow up was 3,31±2,88 years. We divided the patients into two groups, depending on the intensity of IgA deposits: G1 n=29 (+1/+2), G2 n=52 (+3/+4); depending on the localizations of these deposits, we analyzed 3 groups: A n= 39 (mesangium), B n= 15 (glomeruli vessels), C n=27 (both) and depending on the kind of deposits we analyzed 4 groups: gr. a - n=30 (only IgA), gr. b - n=37 (IgA+C3), gr. c - n=5 (IgA+IgG) gr. d - n= 9 (IgA+IgG+C3). RESULTS: At OOD and FU we not found any differences in G1 vs G2 for: age, proteinuria, GFR and OC in renal biopsy; at FU GFR<90 ml/ min/1,73 m2 FU was observed more frequently in G2 vs G1 (p=0,02). The differences in groups A,B,C and groups a,b,c,d were not found. CONCLUSIONS: Poor prognosis in childhood IgAN may also depend on the intensity of the deposits, irrespective of their location.

Asunto(s)

Glomerulonefritis por IGA/patología , Inmunoglobulina A/análisis , Riñón/patología , Adolescente , Biopsia , Niño , Preescolar , Femenino , Estudios de Seguimiento , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/metabolismo , Humanos , Inmunoglobulina G/análisis , Riñón/química , Riñón/metabolismo , Masculino , Proteinuria , Estudios Retrospectivos

RESUMEN

Monoclonal gammopathy of renal significance (MGRS) regroups renal disorders caused by a monoclonal immunoglobulin without overt hematological malignancy. MGRS includes tubular disorders, glomerular disorders with organized deposits, and glomerular disorders with non-organized deposits, such as proliferative glomerulonephritis with monoclonal IgG deposits. Since glomerular involvement related to monotypic IgA deposits is poorly described we performed retrospective analysis and defined clinico-biological characteristics, renal pathology, and outcome in 19 referred patients. This analysis allowed distinction between 2 types of glomerulopathies, α-heavy chain deposition disease (5 patients) and glomerulonephritis with monotypic IgA deposits (14 patients) suggestive of IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits in 12 cases. Clinicopathologic characteristics of α-heavy chain deposition disease resemble those of the γ-heavy chain disease, except for a higher frequency of extra-capillary proliferation and extra-renal involvement. IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits should be differentiated from diseases with polytypic IgA deposits, given distinct clinical, histological, and pathophysiological features. Similarly to IgG-proliferative glomerulonephritis with monoclonal immunoglobulin deposits, overt hematological malignancy was infrequent, but sensitive serum and bone marrow studies revealed a subtle plasma cell proliferation in most patients with IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Anti-myeloma agents appeared to favorably influence renal prognosis. Thus, potential progression towards symptomatic IgA multiple myeloma suggests that careful hematological follow-up is mandatory. This series expands the spectrum of renal disease in MGRS.

Asunto(s)

Glomerulonefritis por IGA/inmunología , Glomerulonefritis/inmunología , Enfermedad de las Cadenas Pesadas/inmunología , Inmunoglobulina A/análisis , Riñón/inmunología , Mieloma Múltiple/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biopsia , Proliferación Celular , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Técnica del Anticuerpo Fluorescente , Francia , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/patología , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/patología , Enfermedad de las Cadenas Pesadas/tratamiento farmacológico , Enfermedad de las Cadenas Pesadas/patología , Humanos , Cadenas alfa de Inmunoglobulina/análisis , Cadenas gamma de Inmunoglobulina/análisis , Riñón/efectos de los fármacos , Riñón/ultraestructura , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Tiempo

RESUMEN

BACKGROUND: Little information is currently available on the development of tubulointerstitial lesions in children with Henoch-Schönlein nephritis (HSN). To identify the impact of the development of tubulointerstitial changes in HSN, we retrospectively analyzed renal biopsies obtained from children with HSN. METHODS: Twenty-eight children with HSN from whom serial renal biopsies had been obtained before and after immunosuppressive therapy were enrolled in the study. The patients were divided into two groups according to the observed change in tubulointerstitial lesion development: group I (n = 15), with stable or improved tubulointerstitial lesions, and group II (n = 13), with worsened tubulointerstitial lesions. Group II patients had longer duration of proteinuria than group I patients (3.7 ± 3.7 years vs. 1.7 ± 1.7 years, p = 0.052). RESULTS: The change in serum albumin level was negatively correlated with the change in tubulointerstitial scores before and after treatment (γ = -0.444, p = 0.018). Group II patients showed a significant decrease in immunoglobulin G (IgG) and IgA deposits after treatment (p = 0.039 and 0.003, respectively), while group II patients did not (p = 0.458 and 0.506, respectively). CONCLUSIONS: Although the International Study of Kidney Disease in Children classification of HSN does not include tubulointerstitial lesions, they can progress during treatment and could have significant clinical implications in association with the duration of proteinuria.

Asunto(s)

Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/patología , Inmunosupresores/uso terapéutico , Riñón/patología , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/patología , Biopsia , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Vasculitis por IgA/sangre , Vasculitis por IgA/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Masculino , Nefritis Intersticial/sangre , Nefritis Intersticial/inmunología , Proteinuria/orina , Estudios Retrospectivos , Albúmina Sérica/análisis

RESUMEN

AIMS: (1) Assess the population-based incidence of severe olmesartan-associated enteropathy. (2) To describe patients of the Spanish registry. (3) Evaluate markers of potential coeliac disease and associated autoimmunity. METHODS: Crude incidence rates in the area of Terrassa (Catalonia) were calculated. Clinical characteristics of patients in the Spanish registry were collected. Duodenal lymphocyte subpopulations and anti-TG2 IgA deposits were assessed in a subset of patients. RESULTS: Annual incidence rates (2011-2014) ranged from 0 to 22 cases per 10(4) treated patients. Twenty patients were included in the Spanish registry. Nineteen (95%) exhibited villous atrophy and 16 (80%) had severe enteropathy. Lupus-like disease occurred during olmesartan treatment in 3 patients. HLA-DQ2/DQ8 was positive in 64%. Markers of potential coeliac disease were present in 4 out of 8 patients (positive anti-TG2 deposits and/or increased CD3+gammadelta+ intraepithelial lymphocytes and reduced CD3-). Histopathological changes and clinical manifestations including autoimmune disorders improved after olmesartan discontinuation but not after gluten-free diet, irrespective of the presence or absence of coeliac markers. CONCLUSIONS: Incidence of severe olmesartan-associated enteropathy was low. Autoimmune phenomena were present in a subset of cases and reversed after olmesartan removal. A genetic coeliac disease background and the presence of potential coeliac markers might uncover predisposing factors.

Asunto(s)

Antihipertensivos/efectos adversos , Autoanticuerpos/inmunología , Duodeno/inmunología , Enteritis/inducido químicamente , Proteínas de Unión al GTP/inmunología , Imidazoles/efectos adversos , Inmunoglobulina A/inmunología , Linfocitos/inmunología , Tetrazoles/efectos adversos , Transglutaminasas/inmunología , Anciano , Anciano de 80 o más Años , Biomarcadores , Enfermedad Celíaca/genética , Enfermedad Celíaca/inmunología , Enteritis/genética , Enteritis/inmunología , Femenino , Antígenos HLA-DQ/genética , Humanos , Masculino , Persona de Mediana Edad , Proteína Glutamina Gamma Glutamiltransferasa 2 , España

RESUMEN

BACKGROUND: IgA pemphigus is a particular entity among autoimmune blistering intraepidermal diseases. IgA pemphigus is subdivided into two types: intraepidermal neutrophilic IgA dermatosis and subcorneal pustular dermatosis. PATIENTS AND METHODS: We report the case of an 82-year-old woman with intraepidermal neutrophilic IgA pemphigus associated with IgA gammopathy. The histopathological findings were unusual, with numerous large subcorneal pustules, a few pustules in the stratum spinosum, and basal IgA deposition. A favourable outcome was achieved with acitretin. DISCUSSION: This observation is significant in that it highlights the difficulty of classification of IgA pemphigus, which is currently based on clinical and histopathological findings. There is currently no therapeutic consensus attitude but simply a set of empirical data.

Asunto(s)

Acitretina/uso terapéutico , Inmunoglobulina A/sangre , Cadenas kappa de Inmunoglobulina/sangre , Queratolíticos/uso terapéutico , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Pénfigo/tratamiento farmacológico , Anciano de 80 o más Años , Betametasona/uso terapéutico , Proteína C-Reactiva/análisis , Dapsona/uso terapéutico , Femenino , Humanos , Inmunoglobulina A/análisis , Infiltración Neutrófila , Pénfigo/complicaciones , Pénfigo/inmunología , Pénfigo/patología , Recurrencia , Piel/inmunología , Piel/patología

RESUMEN

La dermatosis por IgA lineal de la infancia es una enfermedad ampollar, auto inmune, adquirida, usualmente en la edad pre-escolar. Histológicamente se observa una ampolla subepidérmica y en la inmunofluorescencia directa, depósitos lineales de IgA. La respuesta al tratamiento es generalmente favorable. Presentamos una paciente femenina de 3 años de edad, con cuadro de cinco días de aparición de máculas eritematosas, pruriginosas en extremidades y tronco, sobre los cuales luego de una día aparecieron vesículas y ampollas. Se le realiza biopsia de piel e inmunofluorescencia directa las cuales confirman el diagnóstico de dermatosis de IgA lineal de la infancia. Se inicia tratamiento con corticoides tópicos y endovenosos, antibióticos y antihistamínicos demostrando mejoría de las lesiones y tendencia a la curación a las 3 semanas de evolución.

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Linear IgA dermatosis of childhood is an autoimmune, bullous, acquired disease, predominantly in pre-school children. Histologically you should observe a sub epidermal bulla, the direct immunofluorescence shows linear deposits of IgA along the basement membrane. Generally there is a good response to treatment. We present the clinical case of a 3 years old girl, who had five days with erythematous, pruriginous, macule in her limbs and trunk, followed by the appearance of vesicles and bulla. We did a skin biopsy and direct immunofluorescence that confirmed the diagnosis of linear IgA dermatosis of childhood. We started treatment with topical and systemic steroids, antibiotics and antihistaminic, showing improvement of the lesion at 3 weeks.