The Zenith Syndrome

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In addition, circulating antibodies to cryptic, conformational epitopes within the NC1 domain of the alpha 3 chain of Type IV Collagen are commonly found at the zenith of the clinical disease.

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However, exceptions to these general rules do occur, as exemplified by two remarkable cases reported in this issue of the Clinical Kidney Journal. The possible explanations for and the lessons learned from these uncommon occurrences are discussed in this short commentary. Anti-glomerular basement membrane GBM antibody disease is an uncommon but very well understood autoimmune disease, first delineated by Lerner, Glassock and Dixon in [ 1 ]. It has been known for over two decades that the predominant pathogenic autoantibody is of the IgG isotype and is directed to epitopes on the non-collagenous NC domain of Type IV collagen, chiefly, but not exclusively, in a peptide sequence of the alpha 3 chain [ 2 , 3 ].

The two major epitopes Ea and Eb are cryptic and conformational, residing in the hexamer of the alpha 3, 4, 5 chains of Type IV collagen [ 2 ]. Dissolution of sulfilimine bonds and dissociation of the hexamer are required for binding of anti-GBM autoantibodies [ 4 ]. A large number of assays for such autoantibodies have been developed and described, some having commercial applications, while others are primarily of research interest [ 6 — 11 ]. These assays utilize a variety of basement membrane substrates and detection technology [e.

A highly sensitive bio-sensor assay has also recently been described, but is generally not available for clinical use [ 6 ]. Such cases may be detected by IIF [ 8 ]. Furthermore, it is well known that the anti-GBM antibodies in human disease are intrinsically heterogeneous with respect to their reactivity to GBM constituents, but only some anti-GBM antibodies are pathogenic [ 2 , 8 , 13 , 14 ]. The origin of this heterogeneity is uncertain, but might be due to secondary release of altered or cryptic autoantigens from damaged tissue or due to intra- or intermolecular epitope spreading in evolving disease [ 15 ].

Importantly, the assays for anti-GBM antibody utilize a variety of substrates: Thus, the origins of the false-negative results are potentially quite varied. To summarize, they include: These largely anecdotal reports have led to the suggestion that no single test can replace the accuracy of a good quality kidney biopsy and a nephrologist's clinical acumen in diagnosing Goodpasture's disease now known generally as anti-GBM disease [ 18 ]. Of course, a positive anti-GBM assay performed in a respected laboratory has a very high predictive value, in a clinically compatible scenario, approaching It then naturally subsides, often over a protracted period without specific treatment, leaving behind a variable degree of lasting glomerular injury, depending on the magnitude of the initial injury, the timeliness and aggressiveness of treatment, most often associated with the disappearance of circulating anti-GBM antibodies [ 21 , 22 ].

Atypical forms of presumed anti-GBM disease not associated with crescentic GN have been described [ 25 ]. The precise mechanisms underlying this uncommon recurring and relapsing form of anti-GBM disease are obscure, but T-cell-mediated modulation of the immune response has been suggested, based on experimental studies of animal models of the disease [ 16 ]. Both of these phenomena are described in two exceptional case reports published in this issue of the Clinical Kidney Journal by Liu et al.

No pulmonary hemorrhage PH was observed initially. The patient subsequently experienced two relapses, one 5 years after the initial episode, this time with PH and positive anti-GBM. She was treated with PLEX, steroids and cyclophosphamide, the latter for 32 months—a period greatly exceeding usual practice. She improved with treatment and no further relapses have occurred despite continued cigarette smoking.

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Standard therapy again improved the PH, but she was left dialysis-dependent. Like the case of Liu et al. Taken together, these two cases provide an important lesson that a monophasic illness is not inevitable in anti-GBM disease, and detection of anti-GBM antibodies can be quite variable depending on the assay used.

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These observations extend the phenotype of antic-GBM disease. A common feature in these two cases is the continuing exposure to pulmonary irritants and prominent manifestations of PH with relapses. This might explain the repeated bouts of PH in the presence of a low and undetectable by conventional assays levels of possibly low-affinity anti-GBM antibodies.

These antibodies might have been detected by WB or bio-sensor-based assays, which were not performed. The continued presence of linear deposits of IgG in the case of Gu et al. WB or chemiluminescence assays are preferred when the ELISA assays are inextricably negative; however, these assays may be of limited availability.

Periprocedural morbidity included temporary renal failure in 1 patient and postimplantation syndrome with fever and leukocytosis for 23 days in 1 patient. No cases of paraplegia were recorded.

No migration of the device was observed. No late occlusion of the visceral or renal arteries was recorded at follow-up.

Autism associated with conditions characterized by developmental errors in early embryogenesis: Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Chen Y, Bodles AM. Amyloid precursor protein modulates beta-catenin degradation. J Neuroinflammation ; 4: The epidemiology of the dementias: Curr Opin Psychiatry ; Current drug targets for Alzheimer's disease treatment.

Drug Dev Res ; Quantitative MR imaging in Alzheimer disease. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: Am J Med Genet ; Early white-matter abnormalities of the ventral frontostriatal pathway in fragile X syndrome. Dev Med Child Neurol ; Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci ; Mattson MP, Furukawa K. Signaling events regulating the neurodevelopmental triad: Perspect Dev Neurobiol ; 5: Developmental expression of the beta-amyloid precursor protein and heat-shock protein 70 in the cerebral hemisphere region of the rat brain.

Ann NY Acad Sci ; A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. Multiple Gq-coupled receptors converge on a common protein synthesis-dependent long-term depression that is affected in fragile X syndrome mental retardation.


Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons. Glutamate blockade corrects fragile X syndrome in mice: Neurol Today ; 8: FEBS Lett ; Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet ; Gene expression profiles in a transgenic animal model of fragile X syndrome. Neurobiol Dis ; Potential Alzheimer's disease markers for autism?

Beta amyloid precursor protein and acetylcholinesterase correlated with aggression in autism. Presented at the American Academy of Neurology, Seattle, Mol Psychiatry ; Memantine treatment decreases levels of secreted Alzheimer's amyloid precursor protein APP and amyloid beta A beta peptide in the human neuroblastoma cells. Neurosci Lett ; The role of APOE polymorphisms in late-onset dementias. Cell Mol Life Sci ; Association between APOE polymorphisms and predisposition for autism. Psychiatr Genet ; Alzheimer Dis Assoc Disord ; J Autism Dev Disord ; Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease.

Molecular analysis and test of linkage between the FMR-1 gene and infantile autism in multiplex families. Am J Hum Genet ; HLA-A2 homozygosity but not heterozygosity is associated with Alzheimer disease.

The zenith syndrome / Robert Menzies | National Library of Australia

Hum Immunol ; J Alzheimers Dis ; Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry ; 6: Allelic functional variation of serotonin transporter expression is a susceptibility factor for late onset Alzheimer's disease. Serotonin transporter 5-HTT gene variants associated with autism? Hum Mol Genet ; 6: