Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes

Furneaux, Henry; Reich, Lillian; Posner, Jerome B.

doi:10.1212/wnl.40.7.1085

Cited by 190 publications

(81 citation statements)

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“…Albert and J.C. Darnell, unpubl. data), and these antibodies are actively synthesized within the CSF compartment by B cells (Furneaux et al 1990). In addition, the pathologic hallmark of PCD brains is the destruction of Purkinje neurons (Posner 1995;Verschuuren et al 1996;Corradi et al 1997), although the mechanism of cell death is not known.…”

Section: The Role Of the Cdr2:c-myc Interaction In Purkinje Neuronal mentioning

confidence: 99%

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

Okano¹,

Park²,

Corradi³

et al. 1999

Genes & Development

111

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Paraneoplastic cerebellar degeneration (PCD) is a disorder in which breast or ovarian tumors express an onconeural antigen termed cdr2, which normally is expressed in cerebellar Purkinje neurons. This leads to an immune response to cdr2 that is associated with tumor immunity and autoimmune cerebellar degeneration. We have found that cdr2, a cytoplasmic protein harboring a helix-leucine zipper (HLZ) motif, interacts specifically with the HLZ motif of c-Myc. Both proteins colocalize in the cytoplasm of adult cerebellar Purkinje neurons, and coimmunoprecipitate from tumor cell lines and cerebellar extracts. cdr2 down-regulates c-Myc-dependent transcription in cotransfection assays, and redistributes Myc protein in the cytoplasm. Disease antisera from six of six PCD patients specifically blocked the interaction between cdr2 and c-Myc in vitro. These data indicate that cdr2 normally sequesters c-Myc in the neuronal cytoplasm, thereby down-regulating c-Myc activity, and suggest a mechanism whereby inhibition of cdr2 function by autoantibodies in PCD may contribute to Purkinje neuronal death.

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Section: The Role Of the Cdr2:c-myc Interaction In Purkinje Neuronal mentioning

confidence: 99%

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

Okano¹,

Park²,

Corradi³

et al. 1999

Genes & Development

111

View full text Add to dashboard Cite

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“…Evidence supporting this connection has been presented in the case of Eaton-Lambert myasthenic syndrome, a disease of the peripheral nervous system, in which the binding of autoantibodies at the neuromuscular junction interferes with the calcium-induced release of neurotransmitter (DeAizpurua et al, 1988;Kim and Neher, 1988;Newsom-Davis, 1985). An autoimmune component also has been suggested in several diseases of the central nervous system, including paraneoplastic cerebellar degeneration (Anderson et al, 1988;Furneaux et al, 1990;Greenlee and Lipton, 1986) and cancer-associated retinopathy (CAR) t (Buchanan et al, 1984;Grunwald et al, 1985;Keltner et al, 1983;Kornguth et al, 1982;Thirkill et al, 1987Thirkill et al, , 1989.…”

mentioning

confidence: 99%

A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.

Polans

Buczyłko

Crabb

et al. 1991

The Journal of Cell Biology

251

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Abstract. Cancer-associated retinopathy (CAR), a paraneoplastic syndrome, is characterized by the degeneration of retinal photoreceptors under conditions where the tumor and its metastases have not invaded the eye. The retinopathy often is apparent before the diagnosis of cancer and may be associated with autoantibodies that react with specific sites in the retina. We have examined the sera from patients with CAR to further characterize the retinal antigen. Western blot analysis of human retinal proteins reveals a prominent band at 26 kD that is labeled by the CAR antisera. Antibodies to the 26-kD protein were affinity-purified from complex CAR antisera and used for EMimmunocytochemical localization of the protein to the nuclei, inner and outer segments of both rod and cone cells. Other antibodies obtained from the CAR sera did not label photoreceptors. Using the affinitypurified antibodies for detection, the 26-kD protein, designated p26, was purified to homogeneity from the outer segments of bovine rod photoreceptor cells by Phenyl-Sepharose and ion exchange chromatography. Partial amino acid sequence of p26 was determined by gas phase Edman degradation and revealed extensive homology with a cone-specific protein, visinin. Based upon structural relatedness, both the p26 rod protein and visinin are members of the calmodulin family and contain calcium binding domains of the E-F hand structure.variety of neurodegenerative diseases are known to be associated with different types of cancer, even though the tumor and its metastases have not invaded the nervous system (Brain and Norris, 1965;Brain and Wilkinson, 1965;

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“…The levels of antineuronal antibodies in serum and CSF before and after PLEX dropped only in serum, whereas CSF levels remained unchanged, but Q Alb and Q IgG were not reported 32, 33. The IgG CSF/serum ratio increased after PLEX in most cases (anti‐Yo and anti‐Hu).…”

Section: Discussionmentioning

confidence: 96%

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation

Bonnan

Gianoli-Guillerme

Courtade

et al. 2018

Ann Clin Transl Neurol

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ObjectiveThe low level of passively diffused IgG through the blood–brain barrier is sufficient to blur the estimation of intrathecal IgG synthesis (ITS). Therefore, this estimation requires a mathematical calculation derived from empirical laws, but the range of normal values in healthy controls is wide enough to prevent a precise calculation. This study investigated the precision of various methods of ITS estimations and their application to two clinical situations: plasma exchange and immune suppression targeting ITS.MethodsBased on a mathematical model of ITS, we constructed a population of healthy controls and applied a tunable ITS.ResultsWe demonstrate the following results: underestimation of ITS is common at individual level but true ITS is well fitted by cohorts; Q IgG increases after plasma exchange; IgG Loc calculation based on Qlim falsely increases when Q Alb decreases; the sample size required to demonstrate a decrease in ITS increases exponentially with larger Q Alb.InterpretationStudies evaluating changes in ITS level should be adjusted to Q Alb. Low amounts of ITS could be largely underestimated.

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Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes

Cited by 190 publications

References 0 publications

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation

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