Anti-brush Border Antibodies Research Articles

Discovering the Etiology of a Rare Diagnosis of Anti-brush Border Antibody (ABBA) Disease

Discovering the Etiology of a Rare Diagnosis of Anti-brush Border Antibody (ABBA) Disease

Kidney Dysfunction in Hematologic Malignancy Unveiling Anti-brush Border Antibody Disease

Kidney Dysfunction in Hematologic Malignancy Unveiling Anti-brush Border Antibody Disease

Anti-brush Border Antibody Disease with Segmental Membranous Nephropathy and Acute Tubular Injury in a Patient with Severe Diabetic Nephropathy

Anti-brush Border Antibody Disease with Segmental Membranous Nephropathy and Acute Tubular Injury in a Patient with Severe Diabetic Nephropathy

#1941 About a case: ABBA disease in a patient with thymoma

Abstract Background and Aims ABBA (antibrush border antibody) disease is a rare autoimmune tubulointerstitial kidney disease with few descriptions in the literature. Diagnosis is based on light microscopy, immunofluorescence, electron microscopy and immunostaining for LRP2 (LDL receptor related protein 2), also known as megalin. Method We report the case of a 47-year-old Caucasian man admitted in January 2023 for oedema and acute kidney injury (creatinine 3 mg/dl). Biology revealed nephrotic syndrome with hypoalbuminemia (12 g/L) and albuminuria (13 g/g). Haematuria was also noted (75/mm3). His medical history was notable for myasthenia gravis and epithelial Gougerot. Serological tests were negative for HIV, hepatitis B and hepatitis C. Anti-GBM and anti-PLA2R were negative, antinuclear antibodies and antineutrophil cytoplasmic antibodies were both positive at 1/80 without specificity. Serum complement (C3 and C4) and protein electrophoresis were normal. Renal biopsy showed membranous nephropathy, anti-PLA2R, anti-THSD7A, NELL1 and EXT1/2 negative. There was also IgG staining along Bowman's capsule and along part of the tubular basement membrane (TBM). The acute tubular injury was severe. Morphological studies with thoracic tomodensitometry, thoracic MRI and PET scan revealed a thymoma. The patient underwent surgery in May. It was a stage 3 thymoma with pulmonary and pericardial invasion. In June 2023, the patient started haemodialysis due to progression of chronic renal failure. We performed a second renal biopsy, which confirmed the atypical membranous nephropathy with glomerular and tubular deposits and 10% interstitial sclerosis. The patient received two injections of RITUXIMAB (30 June and 14 July 2023). Results In October 2023, we performed a third renal biopsy due to dialysis dependency three months after RITUXIMAB. The glomerular lesions were similar to the previous biopsy, with minimal extra-membranous deposits. However, tubulointerstitial lesions were more pronounced than before. There was 25% tubular atrophy and 25% interstitial sclerosis associated with interstitial inflammation. We also identified anti-LRP2 immune deposits along the TBM. All these histopathological features lead to the diagnosis of ABBA. Conclusion Anti-LRP2 nephropathy is an orphan disease. It's caused by autoantibodies directed against the proximal tubular brush border, leading to a progressive decline in kidney function. The largest recently published cohort includes 67 patients. Many patients may be misdiagnosed due to the insidious onset and atypical presentation with concomitant glomerular or tubulointerstitial disease. In the cohort, 30% of patients had cancer, including solid organ malignancies (including 1 thymoma). It seems that combined treatment with corticosteroids and another immunosuppressive therapy (cyclophosphamide or rituximab) has better results. In our case, despite his thymoma surgery and rituximab perfusions, the patient is still on dialysis. The immunosuppressive treatment will be discussed with the oncologist soon.

Clinicopathologic Features of Antibrush Border Antibody Disease

Antibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management. We identified 67 patients with ABBA who underwent kidney biopsy, including 65 native and 2 transplants. Demographics, clinical findings, and laboratory data were obtained. Histopathologic data included light microscopy, immunofluorescence, electron microscopy and immunostaining for LRP2, CUBN, and AMN. Follow-up data, including treatment(s), laboratory values, and outcomes, were available from 51 patients. Patients with ABBA were predominantly male with a median age of 72 years. Median serum creatinine was 2.7 mg/dl, proteinuria was 2.8 g/day, and hematuria was present in two-thirds of the patients. Tubular injury with LRP2-positive tubular basement membrane (TBM) deposits were seen in 94.2% of patients. Thirty-eight patients (56.7%) had a second kidney disease, commonly glomerular diseases with high-grade proteinuria. These diseases included podocytopathies, membranous nephropathy (MN), IgA nephropathy, diabetic glomerulopathy, lupus nephritis (LN), crescentic glomerulonephritis (GN), tubulointerstitial nephritis, and involvement by lymphoma. The majority of patients were treated with immunosuppression. Of those patients with follow-up, 29.4% achieved remission, 70.6% had no response, and 52.8% required dialysis or were deceased. Untreated patients were at the highest risk. ABBA is a rare autoimmune kidney disease that often occurs with other kidney diseases. Although the overall prognosis of ABBA is poor, there is potential benefit from immunosuppression.

Clinicopathologic Features of Anti-Brush Border Antibody Disease: A Series of 66 Patients

Clinicopathologic Features of Anti-Brush Border Antibody Disease: A Series of 66 Patients

A Case of Anti-Brush Border Antibody Disease

A Case of Anti-Brush Border Antibody Disease

Cubilin and amnionless protein are novel target antigens in anti–brush border antibody disease

The kidney proximal tubule reabsorbs large amounts of low-molecular-weight proteins, albumin, electrolytes, and solutes from the glomerular filtrate to the systemic circulation. Alteration of the specialized transport systems that operate in the brush border of proximal tubule cells leads to urinary loss of these molecules and compromises homeostasis.1,S5

LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti-Brush Border Antibody Disease.

Primary renal tubulointerstitial disease resulting from proximal tubule antigen-specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.

Lack of Any Relationship Between Circulating Autoantibodies and Interleukin–6 Levels in Egyptian Patients Infected with the Hepatitis C Virus

Introduction:Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients.Methods:Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence.Results:Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent.Conclusions:IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.

Prognostic Factors in Sudden Sensorineural Hearing Loss: Our Experience and a Review of the Literature

We investigated prognostic factors in sudden sensorineural hearing loss (SSNHL). Our study group consisted of 133 patients with SSNHL who were treated at our department between 1980 and 2000. Eighty-one of them (group B) were treated between 1980 and 1996; they received vasodilators and small doses of steroids. The others (52 patients; group A) were treated between 1997 and 2000; they received vasodilators, steroids at high doses, and hyperbaric oxygen. A multivariate stepwise linear regression was used to identify the prognostic factors that were related to hearing improvement as measured by objective change of gain in the overall average (0.5, 1, 2, 4, 6, 8 kHz), the pure tone average (0.5, 1, 2 kHz), the high tone average (4, 6, 8 kHz), and the pure middle tone average (0.5, 1, 2, 4 kHz). The following factors were included in the analysis: group (method of treatment), age, gender, seasonal occurrence of disease, presence of tinnitus and vestibular symptoms, time delay before first visit, type of initial audiogram, and type of caloric reaction. In group A, an additional analysis was conducted to include the results of certain laboratory tests: blood morphology parameters, erythrocyte sedimentation rate, glucose level, coagulogram, lipidogram, thyroid-stimulating hormone, autoantibodies (antimitochondrial antibodies, smooth muscle antibodies, and anti-brush border antibodies), and immunoglobulins G, A, and M. Values for p of less than .05 were considered significant. Our analysis suggests the presence of the following prognostic factors for SSNHL: method of SSNHL treatment (better results in group A); time delay before the start of treatment (better results when treatment started within 10 days of the first symptoms of SSNHL); and type of caloric reactions (worse results in patients with canal paresis). In group A, the factors for poor prognosis for absolute hearing improvement were as follows: delayed treatment, labyrinth responsiveness disorders, and decreased level of thyroid-stimulating hormone. In group A, better hearing improvement was observed in those patients in whom SSNHL was diagnosed in the spring. A short time delay before starting treatment (within 10 days), treatment with high doses of steroids and hyperbaric oxygen, preserving complete caloric function of the labyrinths, normal function of the thyroid, and seasonal occurrence of the disease in the spring were positive prognostic factors for hearing recovery in SSNHL.

Frequency and Levels of Autoantibodies in Healthy Adult Omanis

A previous pilot study showed a high frequency of anti-smooth muscle autoantibody in Omani blood donors and pregnant women. We conducted this larger-scale study to investigate the frequency and significance of several autoantibodies in healthy individuals from different regions of Oman. Sera obtained from 1537 healthy Omanis (1153 males and 384 females), ranging in age from 18 to 57 years, were tested for the presence of ten different autoantibodies using indirect immunofluorescence, haemagglutination and latex agglutination techniques. Low levels of autoantibodies were detected in 33.5%, whereas a few individuals (1.8%) showed high autoantibody titres. Anti-smooth muscle autoantibodies (ASMA) were the most prevalent (11%). Anti-nuclear autoantibodies (ANA) were the second most prevalent (7.6%). Anti-thyroid microsomal autoantibodies (ATMA) and anti-thyroglobulin autoantibodies (ATA) were present in 6.5% and 4.4% of individuals, respectively. The other autoantibodies were detected much less frequently: anti-parietal cells autoantibodies (APCA) were found in 1.6%, anti-brush border antibodies (ABBA) in 1.3%, anti-reticulin autoantibodies (ARA) in 1%, antimitochondrial antibodies (AMA) in 0.8%, antiglomerular basement membrane antibodies (AGBMA) in 0.7% and rheumatoid factor (RF) in 0.4%. The data indicate that autoantibodies are present in healthy Omani individuals, and therefore caution should be taken when interpreting laboratory results of patients suspected of having autoimmune disease.

Anti-brush border antibodies (ABBA) in Crohn's disease: Anything new?

Anti-brush border antibodies (ABBA) in Crohn's disease: Anything new?

Pathogenesis of passive Heymann glomerulonephritis: chlorpromazine inhibits antibody-mediated redistribution of cell surface antigens and prevents development of the disease.

Two hypotheses were tested: first, that in LEW rats the interaction of sheep (or rabbit) anti-brush border antibodies with antigens (Heymann antigens) expressed on the plasma membrane of glomerular visceral epithelial cells is characterized by initial redistribution of immune complexes on the cell surface and by subsequent shedding of immune complexes in the subepithelial part of the capillary wall; and secondly, that this interaction is inhibited by chlorpromazine, a drug that displaces calcium ions from binding sites linking the plasma membrane to the cytoskeleton, and which blocks the redistribution of IgG on the surface of B lymphocytes exposed to anti-IgG antibodies. The studies were performed in vitro on cultured LEW glomerular epithelial cells and in vivo in LEW rats. In cultured glomerular epithelial cells exposed at 37 degrees C to anti-brush border IgG, chlorpromazine prevented, in a dose-dependent manner, the redistribution ("capping") of Heymann antigens and the fixation of complement. The renal glomeruli of chlorpromazine-treated LEW rats examined 6 and 48 hr after transfer of anti-brush border antibodies had punctate and, later, punctate and diffuse deposits of sheep (or rabbit) IgG on glomerular epithelial cells, but not similar deposits of rat C3. Moreover, granular subepithelial deposits of sheep (or rabbit) IgG and rat C3, characteristic of passive Heymann glomerulonephritis, did not develop, although deposits of sheep IgG were detected by immunoelectron microscopy on the microvilli of glomerular epithelial cells. Comparative studies on rats with similar reductions in glomerular filtration rates, produced by high doses of chlorpromazine or with renal artery stenosis, showed that the findings were not the consequence of insufficient delivery of antibody to glomerular epithelial cells. The results are consistent with the interpretation that Heymann glomerulonephritis is induced by mechanisms of redistribution of cell surface antigens comparable to those that govern the interaction of surface antigens (or receptors) with appropriate ligands in B lymphocytes and other classical in vitro systems.

Reabsorption of horseradish peroxidase by proximal tubules in rats with Heymann nephritis.

The distribution of the histochemical protein tracer, horseradish peroxidase, was studied in proximal tubules of rats with Heymann nephritis. Peroxidase reabsorption was substantially reduced in stage 2 of Heymann nephritis, a period during which the brush border of proximal tubules is severely damaged by specific antibodies. Impairment of the reabsorption function could not be attributed either to proteinuria or disturbances of proximal tubule metabolism and appeared to result from loss of microvilli. Recovery of brush border membrane morphology in stage 4 of Heymann nephritis was not accompanied by recovery of the normal capacity to reabsorb peroxidase. Functional deficits resulting from immunologic injury to proximal tubules in Heymann nephritis may persist despite waning of the anti-brush border antibody response and regeneration of the brush border of proximal tubule cells.

Experimental autoimmune Heymann nephritis induced by immunization with rabbit anti-brush border antibody associated glomeruli

Experimental autoimmune Heymann nephritis induced by immunization with rabbit anti-brush border antibody associated glomeruli

The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border.

Purified brush border fractions prepared from rat kidneys were solubilized in detergent, iodinated, and subjected to immunoprecipitation to identify the pathogenic antigen present in brush border membranes that is responsible for the production of Heymann nephritis (HN). Purified IgG prepared from the sera of rabbits or rats immunized with a crude cortical preparation, known as Fx1A, precipitated multiple peptides, whereas IgG eluted from glomeruli of rats with active or passive HN specifically immunoprecipitated a single large glycoprotein (Mr = 330,000). This protein (gp330) was subsequently purified by gel filtration and lentil lectin affinity chromatography from detergent-solubilized brush border membranes. When rats were immunized with purified gp330, they developed anti-brush border antibodies and active HN. IgG prepared from the serum of rats with active HN caused passive HN when injected into normal recipients. Rats immunized against brush border membrane proteins depleted of gp330 developed anti-brush border antibodies but did not develop HN. Further analysis of gp330 indicated that it is solubilized by detergent treatment of isolated brush border microvilli, and its antigenic component is released from intact microvilli by trypsin. By immunoperoxidase staining it was localized to the luminal side of the brush border membranes. These results indicate that (i) gp330 is the pathogenic antigen of HN; (ii) the antigen is a glycoprotein of the brush border membrane; and (iii) it is disposed with its pathogenic domain(s) facing the tubule lumen.

Experimental induction of glomerulonephritis mediated by anti-glomerular basement membrane and anti-brush border antibodies in a single rat.

This report describes induction of nephritis, which was concurrently mediated by [anti-glomerular basement membrane antibody (anti-GBM) and anti-brush border antibody, in the Wistar rat immunized with a solubilized renal antigen (S-RA). The antigen was prepared by digestion of rat cortical tissue with trypsin and pronase. Ouchterlony test using antisera to the rat GBM and brush border showed that the S-RA contained both antigens. From the S-RA the brush border antigen was isolated by affinity chromatography. At the 8th week rats injected with the S-RA showed a linear or combined linear and granular distribution of rat IgG and C3 along the GBM in immunofluorescence. The capillary granular pattern was only observed at the 16th week. In contrast rats injected with the brush border antigen remained in a capillary granular pattern throughout the experimental course. It was suggested that the rat nephritis injected with the S-RA was mediated by the antibodies capable of reacting with at least two different antigens, namely the GBM and the brush border. The possibility was confirmed by demonstrating the coexistence of these two kinds of antibodies in the serum and kidney eluate from the nephritic rats.