scholarly journals The prevalence and immunological features of anti-glomerular basement membrane antibody in patients with HIV

2020 ◽  
Author(s):  
Wenjing Wang ◽  
Xiao-yu Jia Jia ◽  
Zhao Cui ◽  
Yan Chen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Solid Phase ◽  
Chimeric Protein ◽  
Kidney Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hiv Viral Load ◽  
Hiv Patients ◽  
Type Iv

Abstract Background: Anti-glomerular basement membrane disease (GBM) is a kind of chronic autoimmune disease caused by the deposition of circulating anti-GBM antibodies. Non-collagen region of α3 chain of type IV collagen (α3(IV)NC1) is one of the main target antigens. And on α3, EA and EB are the most classical antigen epitopes. It has been reported that anti-GBM antibodies can be detected in HIV patients, but its immunological characteristics are still unclear. In this study, the immunological characteristics of the target antigens were clarified. Methods: Total 93 HIV patients and 20 healthy volunteers were selected in Beijing Youan Hospital from 2017 to 2018. Recombinant human α1-α5(IV)NC1, chimeric protein EA and EB were used as solid phase antigens. Enzyme-linked immunosorbent assay was employed to measure concentrations and subtypes of serum IgG autoantibodies specifically against GBM.Results: Five out of the 93 patients with HIV had low to moderate levels of anti-GBM antibodies. However, these patients presented with no clinical manifestation of any kidney injury or pulmonary hemorrhages. Compared with HIV patients with negative antibodies, there were no significant differences in gender, age, CD4+T cell count and HIV viral load. All sera of five patients recognized non-collagenous domain1 (NC1) of alpha 3 chain of type IV collagen [(α3(IV)NC1] as classic anti-GBM patients, followed by α5(IV)NC1. The antibodies against α3(IV)NC1 were IgG3 predominant, but did not react with either of the classic epitopes on α3 (EA and EB).Conclusion: These data suggest a distinct immunological profile of anti-GBM antibodies in patients with HIV, and might explain the non-pathogenic features of HIV associated anti-GBM antibodies.

scholarly journals The prevalence and immunological features of anti-glomerular basement membrane antibody in patients with HIV

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-jing Wang ◽  
Xiao-yu Jia ◽  
Zhao Cui ◽  
Yan Chen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Kidney Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hiv Viral Load ◽  
Hiv Patients ◽  
Type Iv ◽  
Immunological Profile ◽  
Positive Rate

Abstract Background Anti-glomerular basement membrane disease (GBM) is an autoimmune disease caused by the deposition of circulating anti-GBM antibodies. Non-collagen region of α3 chain of type IV collagen (α3(IV)NC1) is one of the main target antigens, in which EA and EB are the most classical antigen epitopes. It has been reported that anti-GBM antibodies can be detected in HIV patients; however, its immunological characteristics are still unclear. Objectives In this study, the positive rate of the anti-GBM antibodies in HIV and the immunological characteristics of the target antigens were clarified. Methods A total of 93 HIV patients diagnosed in Beijing Youan Hospital from November 2017 to January 2018 were included. Enzyme-linked immunosorbent assay was used to measure the serum IgG autoantibodies specifically against GBM in these patients, as well as their subtypes and antigen spectra. Results It was found that five out of the 93 patients with HIV had low to moderate levels of anti-GBM antibodies. However, these patients presented with no clinical manifestation of any kidney injury or pulmonary hemorrhages. Compared with HIV patients with negative antibodies, there were no significant differences in gender, age, CD4+T cell count and HIV viral load. All sera of five patients recognized non-collagenous domain1 (NC1) of alpha 3 chain of type IV collagen [(α3(IV)NC1] as classic anti-GBM patients, followed by α5(IV)NC1. The antibodies against α3(IV)NC1 were IgG3 predominant, while these antibodies did not react with either of the classic epitopes on α3 (EA and EB). Conclusion These data suggest a distinct immunological profile of anti-GBM antibodies in patients with HIV, and might explain the non-pathogenic features of HIV associated anti-GBM antibodies.

scholarly journals The prevalence and immunological features of anti-glomerular basement membrane antibody in patients with HIV/AIDS

2020 ◽  
Author(s):  
Wenjing Wang ◽  
Xiao-yu Jia Jia ◽  
Zhao Cui ◽  
Yan Chen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Solid Phase ◽  
Chimeric Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hiv Viral Load ◽  
Aids Patients ◽  
Type Iv ◽  
Hiv Aids

Abstract Background Anti-glomerular basement membrane disease (GBM) is an autoimmune disease caused by the deposition of circulating anti-GBM antibodies. The main target antigens are the non-collagen region of the α3(IV)NC1(α3 chain of type IV collagen). EA and EB are two classical antigen epitopes on α3. It has been reported that anti-glomerular basement membrane (GBM) antibodies could be detected in HIV/AIDS patients, but its immunological characteristics are still unclear. In this study, the immunological characteristics of the target antigens were clarified.Methods Total 93 HIV/AIDS patients and 20 healthy volunteers were selected in Beijing Youan Hospital from 2017 to 2018. Recombinant humanα1-α5(IV)NC1, chimeric protein E A , E B were used as solid phase antigens. Enzyme-linked immunosorbent assay was employed to measure concentrations and subtypes of serum IgG autoantibodies specially against GBM.Results Five out of the 93 patients with HIV/AIDS had low to moderate levels of anti-GBM antibodies. However, these patients presented with no clinical manifestation of any kidney injury or pulmonary hemorrhages. Compared with HIV/AIDS patients with negative antibodies, there were no significant differences in gender, age, CD4 + T cell count and HIV viral load. All five patients recognized non-collagenous domain1 (NC1) of alpha 3 chain of type IV collagen [(α3(IV)NC1] as classic anti-GBM patients, followed by α5(IV)NC1. The antibodies against α3(IV)NC1 was IgG3 predominant, but did not react with either of the classic epitopes on α3 (E A and E B ).Conclusion These data suggest a distinct immunological profile of anti-GBM antibodies in patients with HIV/AIDS, and might explain the non-pathogenic features of HIV/AIDS associated anti-GBM antibodies.

scholarly journals The prevalence and immunological features of anti-glomerular basement membrane antibody in patients with HIV

2020 ◽  
Author(s):  
Wenjing Wang ◽  
Xiao-yu Jia Jia ◽  
Zhao Cui ◽  
Yan Chen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Kidney Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hiv Viral Load ◽  
Hiv Patients ◽  
Type Iv ◽  
Immunological Profile ◽  
Positive Rate

Abstract Background: Anti-glomerular basement membrane disease (GBM) is an autoimmune disease caused by the deposition of circulating anti-GBM antibodies. Non-collagen region of α3 chain of type IV collagen (α3(IV)NC1) is one of the main target antigens, in which EA and EB are the most classical antigen epitopes. It has been reported that anti-GBM antibodies can be detected in HIV patients; however, its immunological characteristics are still unclear. Objectives: In this study, the positive rate of the anti-GBM antibodies in HIV and the immunological characteristics of the target antigens were clarified. Methods: A total of 93 HIV patients diagnosed in Beijing Youan Hospital from November 2017 to January 2018 were included. Enzyme-linked immunosorbent assay was used to measure the serum IgG autoantibodies specifically against GBM in these patients, as well as their subtypes and antigen spectra.Results: It was found that five out of the 93 patients with HIV had low to moderate levels of anti-GBM antibodies. However, these patients presented with no clinical manifestation of any kidney injury or pulmonary hemorrhages. Compared with HIV patients with negative antibodies, there were no significant differences in gender, age, CD4+T cell count and HIV viral load. All sera of five patients recognized non-collagenous domain1 (NC1) of alpha 3 chain of type IV collagen [(α3(IV)NC1] as classic anti-GBM patients, followed by α5(IV)NC1. The antibodies against α3(IV)NC1 were IgG3 predominant, while these antibodies did not react with either of the classic epitopes on α3 (EA and EB).Conclusion: These data suggest a distinct immunological profile of anti-GBM antibodies in patients with HIV, and might explain the non-pathogenic features of HIV associated anti-GBM antibodies.

scholarly journals Identification of a multifunctional, cell-binding peptide sequence from the a1(NC1) of type IV collagen.

1990 ◽  
Vol 111 (4) ◽  
pp. 1583-1591 ◽  
Author(s):  
E C Tsilibary ◽  
L A Reger ◽  
A M Vogel ◽  
G G Koliakos ◽  
S S Anderson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Solid Phase ◽  
Peptide Sequence ◽  
Cell Binding ◽  
Type Iv ◽  
Specific Manner ◽  
Dose Dependent ◽  
Nc1 Domain

We have previously identified three distinctive amino acid sequences from type IV collagen which specifically bound to heparin and also inhibited the binding of heparin to intact type IV collagen. One of these chemically synthesized domains, peptide Hep-I, has the sequence TAGSCLRKFSTM and originates from the a1(noncollagenous [NC1]) chain of type IV collagen (Koliakos, G. G., K. K. Koliakos, L. T. Furcht, L. A. Reger, and E. C. Tsilibary. 1989. J. Biol. Chem. 264:2313-2323). We describe in this report that this same peptide also bound to intact type IV collagen in solid-phase assays, in a dose-dependent and specific manner. Interactions between peptide Hep-I and type IV collagen in solution resulted in inhibition of the assembly process of this basement membrane glycoprotein. Therefore, peptide Hep-I should represent a major recognition site in type IV collagen when this protein polymerizes to form a network. In addition, solid phase-immobilized peptide Hep-I was able to promote the adhesion and spreading of bovine aortic endothelial cells. When present in solution, peptide Hep-I competed for the binding of these cells to type IV collagen- and NC1 domain-coated substrata in a dose-dependent manner. Furthermore, radiolabeled peptide Hep-I in solution also bound to endothelial cells in a dose-dependent and specific manner. The binding of radiolabeled Hep-I to endothelial cells could be inhibited by an excess of unlabeled peptide. Finally, in the presence of heparin or chondroitin/dermatan sulfate glycosaminoglycan side chains, the binding of endothelial cells to peptide Hep-I and NC1 domain-coated substrates was also inhibited. We conclude that peptide Hep-I should have a number of functions. The role of this type IV collagen-derived sequence in such diverse phenomena as self-association, heparin binding and cell binding and adhesion makes Hep-I a crucial domain involved in the determination of basement membrane ultrastructure and cellular interactions with type IV collagen-containing matrices.

scholarly journals Possible Implication of Intermolecular Epitope Spreading in the Production of Anti-Glomerular Basement Membrane Antibody in Anti-Neutrophil Cytoplasmic Antibody-associated Vasculitis

2021 ◽  
Author(s):  
Yuka Nishibata ◽  
Mayu Nonokawa ◽  
Yuto Tamura ◽  
Rio Higashi ◽  
Ku Suzuki ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Collagen Type Iv ◽  
Normal Kidney ◽  
Type Iv ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Α3 Subunit

Abstract ObjectiveAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is sometimes complicated by anti-glomerular basement membrane (GBM) disease. Proteases, including elastase, released from neutrophils activated by ANCA are implicated in the pathogenesis of AAV. Epitopes of anti-GBM antibody exist in the α3-subunit non-collagenous (NC1) domain of collagen type IV [Col (IV)]. This region, called α3(IV)NC1, is structurally cryptic. This study aimed to determine the production mechanism of anti-GBM antibody in AAV.MethodsWe first examined whether α3(IV)NC1 could be revealed by the digestion of formalin-fixed, paraffin-embedded (FFPE) normal kidney sections and Col (IV) by proteases, including neutrophil elastase, using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Next, the reveal of α3(IV)NC1 and the infiltration of CD11c+ macrophages in the affected kidneys were evaluated by IHC and immunofluorescent staining using FFPE sections. Finally, the production of anti-GBM antibody in AAV rats was determined by ELISA.Resultsα3(IV)NC1 was revealed by the digestion of FFPE normal kidney sections and Col (IV) by proteases. Although the reveal of α3(IV)NC1 was observed in sclerotic glomeruli regardless of causative diseases, CD11c+ macrophages near α3(IV)NC1 were characteristics of AAV. Anti-GBM antibody was produced subsequent to ANCA in some AAV rats. IHC demonstrated the reveal of α3(IV)NC1 in affected renal tissues and the infiltration of CD11c+ macrophages around the sites.ConclusionThe collective findings suggest that, in AAV, proteases released from neutrophils activated by ANCA digest Col (IV) and result in the reveal of α3(IV)NC1, CD11c+ macrophages present GBM epitopes, and then the host’s immune system produce anti-GBM antibody.

IDENTIFICATION OF ??3, ??4, AND ??5 CHAINS OF TYPE IV COLLAGEN AS ALLOANTIGENS FOR ALPORT POSTTRANSPLANT ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODIES

2000 ◽  
Vol 69 (4) ◽  
pp. 679-684 ◽  
Author(s):  
Raghu Kalluri ◽  
Adriana Torre ◽  
Charles F. Shield ◽  
Eric D. Zamborsky ◽  
Michelle C. Werner ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Type Iv

scholarly journals Glomerular Basement Membrane Selective Permeability in Short-term Streptozotocin-induced Diabetic Rats

2000 ◽  
Vol 1 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Michele Doucet ◽  
Irene Londoño ◽  
Amparo Gómez-Pascual ◽  
Moise Bendayan
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Serum Proteins ◽  
Diabetic Rats ◽  
Glomerular Permeability ◽  
Structural Alterations ◽  
Early Stages ◽  
Type Iv ◽  
Basement Membrane Thickening

In diabetes, the glomerular basement membrane undergoes thickening and structural alterations with loss of glomerular permselectivity properties. However, the onset of the alterations at early phases of diabetes is unclear. Aiming to determine the functional and structural alterations of the glomerular wall in the early stages of diabetes, we have studied the distribution of endogenous circulating albumin and type IV collagen in the glomerular basement membrane, using the immunocytochemical approach. The streptozotocin-injected hyperglycemic rat was our animal model. Renal tissues were examined after 10 days, 2, 4 and 6 months of hyperglycemia. Upon immunogold labelings, changes in the glomerular permeability to endogenous albumin were found altered as early as upon ten days of hyperglycemia. In contrast, no structural modifications were detected at this time point. Indeed, glomerular basement membrane thickening and an altered type IV collagen labeling distribution were only observed after four months of hyperglycemia, suggesting that functional alterations take place early in diabetes prior to any structural modification. In order to evaluate the reversibility of the glomerular alterations, two-month-old diabetic animals were treated with insulin. These animals showed a significant restoring of their glomerular permselectivity. Our results suggest a link between glycemic levels and alteration of glomerular permeability in early stages of diabetes, probably through high levels of glycated serum proteins.

scholarly journals RETRACTED: Production and Characterization of Recombinant Rat Non-collagen Domain of α3 Chain of Type IV Collagen α3 (IV) NC1 Antigen

2016 ◽  
Vol 12 (24) ◽  
pp. 98
Author(s):  
Afsana Munni
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Kidney Diseases ◽  
Cell Epitope ◽  
Affinity Column ◽  
Igg Antibody ◽  
Amino Terminal ◽  
Type Iv ◽  
Collagenous Domain

Glomerulonephritis disease is characterized by inflammation of glomeruli or small blood vessels in the kidney which causes kidney diseases. Glomerulonephritis disease deposits the anti-GBM auto antibody in the glomerular basement membrane. The type IV collagen is the main component of glomerular basement membrane that has α3 chain of type (IV) collagen of non-collagenous domain which contains N-terminal 7S domain, a triple helical collagenous domain, and a C- terminal non-collagenous glomerular domain (NC1). The amino terminal of α3 (IV) NC1 that induces the experimental autoimmuno glomerulonephritis (EAG) in rat model has been identified. The recombinant rat α3 (IV)NC1 antigen has nine amino acid span that is consistent with antibody or T cell epitope which is induced in EAG. The research is carried out on the recombinant rat α3 (IV) NC1 production, purification, quantification, and characterization. The circulation of Anti-GBM antibody in glomerular basement membrane can be measured by the ELISA assay. In addition, the recombinant rat antigen is secreted in HEK293 cell supernatant which is purified by Anti-FLAG M2 monoclonal IgG antibody affinity column. In addition, it is characterized and quantified by SDS-PAGE gel electrophoresis and Western blotting techniques.

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